Journal articleCancer Immunol Res · February 3, 2026
Tumor-draining lymph nodes are a pivotal site for antitumor T-cell priming. However, their mechanistic roles in cancer immune surveillance and immunotherapy response remain poorly defined. Intratumor (IT) virotherapy generates antitumor T-cell immunity thr ...
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Journal articlemedRxiv · April 25, 2025
Intratumor (IT) inoculation of the rhino:poliovirus chimera, PVSRIPO, yielded objective radiographic responses with long-term survival in 20% of patients with recurrent glioblastoma (rGBM). PVSRIPO infects dendritic cells (DCs) and sets up non-cytopathogen ...
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Journal articleJ Neurosurg Pediatr · April 1, 2024
OBJECTIVE: Relatively little is known about the safety and accuracy of catheter placement for oncolytic viral therapy in children with malignant brain tumors. Accordingly, this study combines data from two phase I clinical trials that employed viral immuno ...
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Journal articleSLAS Discov · March 2024
Pediatric brain tumors (PBTs) represent about 25 % of all pediatric cancers and are the most common solid tumors in children and adolescents. Medulloblastoma (MB) is the most frequently occurring malignant PBT, accounting for almost 10 % of all pediatric c ...
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Journal articleCancers (Basel) · September 18, 2023
Brain tumor-initiating cells (BTICs) and tumor cell plasticity promote glioblastoma (GBM) progression. Here, we demonstrate that clemastine, an over-the-counter drug for treating hay fever and allergy symptoms, effectively attenuated the stemness and suppr ...
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Journal articleNeuro Oncol · September 5, 2023
BACKGROUND: Malignant gliomas commandeer dense inflammatory infiltrates with glioma-associated macrophages and microglia (GAMM) promoting immune suppression, evasion, and tumor progression. Like all cells in the mononuclear phagocytic system, GAMM constitu ...
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Journal articleLancet Child Adolesc Health · July 2023
BACKGROUND: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric ...
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Journal articleJ Immunother Cancer · April 2023
BACKGROUND: Antitumor mechanisms of CD4+ T cells remain crudely defined, and means to effectively harness CD4+ T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4+ T cells hold potential to be leveraged for this purpose. Moreover, the ...
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Journal articleSci Transl Med · February 8, 2023
D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized tha ...
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Journal articleJ Immunother Cancer · January 2023
BACKGROUND: While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. There is an urgent n ...
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Journal articleJ Immunother Cancer · September 2022
BACKGROUND: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also re ...
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Journal articleJ Immunother Cancer · April 2021
BACKGROUND: While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera th ...
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Journal articleNat Commun · January 13, 2021
Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunother ...
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Journal articleNat Commun · January 27, 2020
Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendrit ...
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Journal articleCancer Res · July 1, 2019
Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic ...
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Journal articleJ Immunother Cancer · May 29, 2019
BACKGROUND: D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma. In addition to inherent tumoricidal activity, immunotoxins induce secondary immun ...
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Journal articleNeuro Oncol · March 18, 2019
BACKGROUND: Mutations in telomerase reverse transcriptase promoter (TERTp) and isocitrate dehydrogenase 1 and 2 (IDH) offer objective markers to assist in classifying diffuse gliomas into genetic subgroups. However, traditional mutation detection technique ...
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Journal articleJ Neuropathol Exp Neurol · January 1, 2019
Glioma therapeutic resistance to alkylating chemotherapy is mediated via O6-methylguanine-DNA methyltransferase (MGMT). We hypothesized that a CD45/HAM56/MGMT double-stained cocktail would improve MGMT discrimination in tumor cells versus inflammatory and ...
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Journal articlePLoS One · 2019
Standard treatment, unfortunately, yields a poor prognosis for patients with primary or metastatic cancers in the central nervous system, indicating a necessity for novel therapeutic agents. Immunotoxins (ITs) are a class of promising therapeutic candidate ...
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Journal articleJ Neurooncol · November 2018
INTRODUCTION: Pleomorphic xanthoastrocytoma (PXA) is a rare Grade II and III glioma. Surgical resection is the mainstay of treatment, however, adjuvant therapy is sometimes necessary. Given the rarity of PXA, chemotherapeutic efficacy data is limited. The ...
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Journal articleClin Cancer Res · September 1, 2018
Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, T-cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoin ...
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Journal articleSci Rep · August 21, 2018
The concept that human cancer is in essence a genetic disease driven by gene mutations has been well established, yet its utilization in functional studies of cancer genes has not been fully explored. Here, we describe a simple genetics-based approach that ...
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Journal articleClin Cancer Res · August 1, 2018
Purpose: Conventional therapy for malignant glioma fails to specifically target tumor cells. In contrast, substantial evidence indicates that if appropriately redirected, T cells can precisely eradicate tumors. Here we report the rational development of a ...
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Journal articleJ Neuropathol Exp Neurol · August 1, 2018
Poliovirus oncolytic immunotherapy is a putatively novel approach to treat pediatric brain tumors. This work sought to determine expression of the poliovirus receptor (PVR), CD155, in low-grade and malignant pediatric brain tumors and its ability to infect ...
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Journal articleN Engl J Med · July 12, 2018
BACKGROUND: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating ...
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Journal articleJ Neurooncol · July 2018
BACKGROUND: Sym004 is a mixture of two monoclonal antibodies (mAbs), futuximab and modotuximab, targeting non-overlapping epitopes on the epidermal growth factor receptor (EGFR). Previous studies have shown that Sym004 is more efficient at inducing interna ...
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Journal articleNat Commun · May 25, 2018
The majority of glioblastomas can be classified into molecular subgroups based on mutations in the TERT promoter (TERTp) and isocitrate dehydrogenase 1 or 2 (IDH). These molecular subgroups utilize distinct genetic mechanisms of telomere maintenance, eithe ...
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Journal articleCancer Res · January 1, 2018
Median survival for glioblastoma (GBM) remains <15 months. Human cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recen ...
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Journal articleCancer Res · January 1, 2018
Hotspot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malign ...
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Journal articleInt J Oncol · January 2018
Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors. Unraveling the molecular and genetic complexity that determines GBM's pronounced migratory property could provide new options for therapeutic targeting that may signifi ...
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Journal articleToxicol Rep · 2018
Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in a ...
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Journal articleCancer Manag Res · 2018
BACKGROUND: Squamous non-small cell lung cancer (SqNSCLC), as a leading cause of cancer-related deaths worldwide, has limited treatment options and poor prognosis. Thus, novel targeted therapies are desperately needed. MATERIALS AND METHODS: SqNSCLC cases ...
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Journal articleArch Pathol Lab Med · December 2017
CONTEXT: - The oncolytic polio-rhinovirus recombinant (PVSRIPO) has demonstrated promise in currently ongoing phase I/II clinical trials against recurrent glioblastoma and was granted breakthrough therapy designation by the Food and Drug Administration/Cen ...
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Journal articleCancer Res · November 15, 2017
Inactivating mutations in the transcriptional repression factor Capicua (CIC) occur in approximately 50% of human oligodendrogliomas, but mechanistic links to pathogenesis are unclear. To address this question, we generated Cic-deficient mice and human oli ...
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Journal articleOncotarget · September 29, 2017
Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor, with a median survival of less than one year. Due to enormous difficulties in the acquisition of DIPG specimens and the sophisticated technique required to perform brainstem orthotopic i ...
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Journal articleSci Transl Med · September 20, 2017
Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. Thus, approaches that can overcome immunosuppression and engage antitumor immunity are needed. This study defines the adjuvant and cancer im ...
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Journal articleNeuro Oncol · September 1, 2017
BACKGROUND: Of the 4 medulloblastoma subgroups, Group 3 is the most aggressive but the importance of angiogenesis is unknown. This study sought to determine the role of angiogenesis and identify clinically relevant biomarkers of tumor vascularity and survi ...
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Journal articleProtein Eng Des Sel · September 1, 2017
Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target for cancer immunotherapy due to its high level of expression in a number of malignant tumors, and its essential role in tumor growth and progression. Clinical application of CSPG4-targeting i ...
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Journal articleOncotarget · July 28, 2017
Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor, with a median survival of less than one year. Due to enormous difficulties in the acquisition of DIPG specimens and the sophisticated technique required to perform brainstem orthotopic i ...
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Journal articleMol Cancer Res · May 2017
IDH1 mutations occur in the majority of low-grade gliomas and lead to the production of the oncometabolite, D-2-hydroxyglutarate (D-2HG). To understand the effects of tumor-associated mutant IDH1 (IDH1-R132H) on both the neural stem cell (NSC) population a ...
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Journal articleClin Cancer Res · April 15, 2017
Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can e ...
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Journal articleAppl Microbiol Biotechnol · April 2017
D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initia ...
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Journal articleJ Immunol Methods · March 2017
Monoclonal antibodies have become essential tools for diagnostic and therapeutic purposes. Antibody affinity is one of the critical factors influencing the therapeutic success of tumor-targeting antibodies. Therefore, developing an accurate and reliable me ...
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Journal articleOncotarget · November 29, 2016
Intratumoral inoculation of viruses with tumor-selective cytotoxicity may induce cancer cell death and, thereby, shrink neoplastic lesions. It is unlikely, however, that viral tumor cell killing alone could produce meaningful, durable clinical responses, a ...
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Journal articleCancer Res · September 1, 2016
Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genet ...
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Journal articleInvest New Drugs · April 2016
D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2 ...
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Journal articleLancet Oncol · April 2016
BACKGROUND: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensi ...
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Journal articleCancer Immunol Res · March 2016
Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Seve ...
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Journal articleCancer Cell · January 11, 2016
The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit t ...
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Journal articleCancer Immunology Research · January 1, 2016
AbstractIntroduction: Tumor-targeted therapies that efficiently eliminate malignant cells and in the process engage the innate and adaptive immune system are desirable for preventing cancer recurrence. We ha ...
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Journal articleReceptors Clin Investig · 2016
Glioblastoma is the most aggressive malignant brain tumor among all primary brain and central nervous system tumors. The median survival time for glioblastoma patients given the current standard of care treatment (surgery, radiation, and chemotherapy) is l ...
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Journal articleJ Biol Chem · December 25, 2015
Under normal physiologic conditions, the glutathione S-transferase P1 (GSTP1) protein exists intracellularly as a dimer in reversible equilibrium with its monomeric subunits. In the latter form, GSTP1 binds to the mitogen-activated protein kinase, JNK, and ...
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Journal articleCancer Research · December 1, 2015
AbstractThe risk or presence of metastasis in childhood medulloblastoma represents a substantial cause of morbidity and mortality. Relatively little has been known about the molecular mechanisms of medullobl ...
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Journal articleJ Neurooncol · October 2015
Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies ...
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Journal articleN Engl J Med · June 25, 2015
BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic cl ...
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Journal articleNeuro Oncol · June 2015
BACKGROUND: The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhol ...
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Journal articleJ Neurochem · June 2015
The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characte ...
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Journal articleNature · March 19, 2015
After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vacci ...
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Journal articleOncoimmunology · March 2015
Adoptive cellular therapy (ACT) after lymphodepletive conditioning can induce dramatic clinical responses, but this approach has been largely limited to melanoma due to a lack of reliable methods for expanding tumor-specific lymphocytes from the majority o ...
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Journal articleCancer · November 1, 2014
Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct ...
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Journal articleJ Virol · November 2014
UNLABELLED: Protein synthesis, the most energy-consuming process in cells, responds to changing physiologic priorities, e.g., upon mitogen- or stress-induced adaptations signaled through the mitogen-activated protein kinases (MAPKs). The prevailing status ...
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Journal articleJ Clin Invest · October 2014
Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GB ...
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Journal articleJ Clin Invest · September 2014
Aberrant activation of EGFR in human cancers promotes tumorigenesis through stimulation of AKT signaling. Here, we determined that the discoidina neuropilin-like membrane protein DCBLD2 is upregulated in clinical specimens of glioblastomas and head and nec ...
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Journal articleJ Neurooncol · August 2014
Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the n ...
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Journal articleNat Genet · July 2014
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ...
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Journal articleNeuro Oncol · July 2014
Immunotherapy promises an exquisitely precise therapeutic approach, and substantial evidence suggests that activated T cells can eradicate large tumors, even within the "immunologically privileged" brain. EGFRvIII and isocitrate dehydrogenase 1 (IDH1) muta ...
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Journal articleNeuro Oncol · July 2014
PVSRIPO is the live attenuated, oral (SABIN) serotype 1 poliovirus vaccine containing a heterologous internal ribosomal entry site stemming from human rhinovirus type 2. PVSRIPO recognizes nectin-like molecule-5, an oncofetal cell adhesion molecule and tum ...
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Journal articleNeuro Oncol · July 2014
With the exception of Burkitt lymphoma, almost all solid cancers are susceptible to infection with poliovirus, due to widespread ectopic expression of the poliovirus receptor, the onco-fetal cell adhesion molecule Necl5/CD155. We engineered a profoundly CN ...
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Journal articleNeuro Oncol · July 2014
Malignant cells must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome ...
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Journal articleNeuro Oncol · July 2014
The Cancer Genome Atlas (TCGA) Network recently catalogued recurrent genomic abnormalities in glioblastoma (GBM). This genomic profiling lead to the molecular classification of GBMs into four subtypes: Proneural, Neural, Classical and Mesenchymal. The impo ...
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Journal articleCNS Neurosci Ther · May 2014
AIMS: Down-regulation of AJAP1 in glioblastoma multiforme (GBM) has been reported. However, the expression profiles of AJAP1 in gliomas and the underlying mechanisms of AJAP1 function on invasion are still poorly understood. METHODS: The gene profiles of A ...
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Journal articleOncotarget · March 30, 2014
Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or o ...
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Journal articleOncotarget · March 30, 2014
Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type ...
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Journal articlePLoS One · 2014
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal bra ...
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Journal articleNature Genetics · January 1, 2014
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ...
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Journal articleJ Clin Neurosci · January 2014
Chimeric antigen receptors (CAR)-transduced T cells hold great promise in the treatment of malignant disease. Here, we demonstrate that intracerebral injection with a human, epidermal growth factor receptor variant III (EGFRvIII)-specific, third generation ...
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Journal articleOncoimmunology · December 1, 2013
Both the amplification of the gene coding for wild-type (wt) epidermal growth factor receptor (EGFR) and the overexpression of the EGFR deletion mutant, commonly known as EGFRvIII, are hallmarks of glioblastoma. We have recently reported a novel, recombina ...
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Journal articleOncoimmunology · December 1, 2013
Regulatory T cells (Tregs) play a central role in in tumor escape from immunosurveillance. We report that a bispecific T-cell engager (BiTE) targeting a mutated form of the epidermal growth factor receptor, i.e., EGFRvIII, potently redirects Tregs to kill ...
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Journal articleActa Neuropathologica · December 1, 2013
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not ...
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Journal articleOncoimmunology · December 1, 2013
Both the amplification of the gene coding for wild-type (wt) epidermal growth factor receptor (EGFR) and the overexpression of the EGFR deletion mutant, commonly known as EGFRvIII, are hallmarks of glioblastoma. We have recently reported a novel, recombina ...
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Journal articleOncoimmunology · December 1, 2013
Regulatory T cells (Tregs) play a central role in in tumor escape from immunosurveillance. We report that a bispecific T-cell engager (BiTE) targeting a mutated form of the epidermal growth factor receptor, i.e., EGFRvIII, potently redirects Tregs to kill ...
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Journal articleJ Neurosurg · December 2013
OBJECT: Recurrent malignant gliomas have inherent resistance to traditional chemotherapy. Novel therapies target specific molecular mechanisms involved in abnormal signaling and resistance to apoptosis. The proteasome is a key regulator of multiple cellula ...
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Journal articleActa Neuropathol · December 2013
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not ...
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Journal articleOncotarget · November 2013
KMT2D (lysine (K)-specific methyltransferase 2D), formerly named MLL2 (myeloid/lymphoid or mixed-lineage leukemia 2, also known as ALR/MLL4), is a histone methyltransferase that plays an important role in regulating gene transcription. In particular, it ta ...
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Journal articleLancet Oncol · November 2013
BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medullobla ...
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Journal articleCell · October 10, 2013
We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature recept ...
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Journal articleNat Genet · October 2013
Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma ...
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Journal articleJ Immunol Methods · September 30, 2013
Developments in the field of bispecific antibodies have progressed rapidly in recent years, particularly in their potential role for the treatment of malignant disease. However, manufacturing stable molecules has proven to be costly and time-consuming, whi ...
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Journal articleCancer Immunol Res · September 2013
A major mechanism by which human regulatory T cells (T(regs)) have been shown to suppress and kill autologous immune cells is through the granzyme-perforin pathway. However, it is unknown whether T(regs) also possess the capacity to kill tumor cells using ...
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Journal articleClin Cancer Res · September 1, 2013
PURPOSE: The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive wi ...
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Journal articleNeurosurgery · August 2013
Current therapies for glioblastoma are limited by ineffective delivery beyond the blood-brain barrier, limited diffusion of regionally-delivered macromolecules, and lack of tumor specificity. Sustained direct intracerebral infusion at slow flow rates [conv ...
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Journal articleFuture Oncol · July 2013
Modest improvement in brain tumor patient survival has been achieved through advances in surgical, adjuvant radiation and chemotherapeutic strategies. However, these traditional approaches have been unsuccessful in permanently controlling these aggressive ...
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Journal articleExpert Rev Clin Pharmacol · July 2013
While advanced surgical techniques, radiation therapy and chemotherapeutic regimens provide a tangible benefit for patients with glioblastoma (GBM), the average survival from the time of diagnosis remains less than 15 months. Current therapy for GBM is lim ...
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Journal articleJ Neurosurg · June 2013
Isocitrate dehydrogenase 1 (IDH1) mutations have been discovered to be frequent and highly conserved in secondary glioblastoma multiforme and lower-grade gliomas. Although IDH1 mutations confer a unique genotype that has been associated with a favorable pr ...
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Journal articleCancer Immunol Immunother · June 2013
B lymphocyte stimulator (BLyS) is a cytokine involved in differentiation and survival of follicular B cells along with humoral response potentiation. Lymphopenia is known to precipitate dramatic elevation in serum BLyS; however, the use of this effect to e ...
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Journal articleInt J Cancer · May 15, 2013
Our study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG and D08-0493MG) and medulloblastoma (D283MED, D425MED and DAOY) xenografts and cell line. We constructed a novel r ...
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Journal article · May 1, 2013
The prospect for high-grade astrocytic tumor patients continues to be dismal, evenwith advances in surgery, radiotherapy, and chemotherapy. There is a need for thedevelopment of novel therapies that would eliminate the heterogeneous and diffuseastrocytic t ...
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Journal articleProc Natl Acad Sci U S A · April 9, 2013
Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thala ...
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Journal articleOncoimmunology · April 1, 2013
Bispecific T-cell engagers (BiTEs) may break multiple barriers that currently limit the use of immunotherapy in glioblastoma patients. We have recently described a novel BiTE specific for a mutated form of the epidermal growth factor receptor, EGFRvIII, th ...
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Journal articleOncotarget · April 2013
A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric ...
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Journal articleJ Biol Chem · March 29, 2013
Glioblastoma multiforme (GBM), like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg effect. Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consum ...
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Journal articleDrugs Future · March 2013
Glioblastoma, the most common primary malignant brain tumor, is among the most difficult cancers to treat. Despite the aggressive standard of care, including surgical removal followed by radiotherapy with concomitant and adjuvant chemotherapy, the often su ...
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Journal articleCancer Res · January 15, 2013
Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually a ...
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Journal articleProc Natl Acad Sci U S A · January 2, 2013
Bispecific antibodies (bscAbs), particularly those of the bispecific T-cell engager (BiTE) subclass, have been shown to effectively redirect T cells against cancer. Previous efforts to target antigens expressed in both tumors and normal tissues have produc ...
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Journal articleNature Genetics · 2013
Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma ...
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Journal articleJ Neurooncol · January 2013
Glioblastoma multiforme (GBM) is a devastating disease with a dismal prognosis and a very limited response to treatment. The current standard of care for GBM usually consists of surgery, radiation and chemotherapy with the alkylating agent temozolomide, al ...
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Journal articlePLoS One · 2013
Temozolomide (TMZ) is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases. A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be ...
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Journal articleMAbs · 2013
About 60 percent of glioblastomas highly express the gangliosides 3'-isoLM1 and 3',6'-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the ...
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Journal articlePLoS One · 2013
The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-based cytoprotective mechanism acting to prevent pathologies accompanying protein aggregation. It is frequently active in tumors, but relatively unstudied in gliomas. We hypothesized that ...
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Journal articleCurr Drug Discov Technol · December 2012
The blood brain barrier (BBB) poses a significant challenge for drug delivery of macromolecules into the brain. Convection-enhanced delivery (CED) circumvents the BBB through direct intracerebral infusion using a hydrostatic pressure gradient to transfer t ...
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Journal articleGenome Res · December 2012
Monoallelic point mutations of the NADP(+)-dependent isocitrate dehydrogenases IDH1 and IDH2 occur frequently in gliomas, acute myeloid leukemias, and chondromas, and display robust association with specific DNA hypermethylation signatures. Here we show th ...
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Journal articleNat Med · December 2012
Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a hi ...
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Journal articleNat Chem Biol · November 2012
Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases to homologous residues in the active sites of homoisocitrate dehydrogenases to derive enzymes that cataly ...
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Journal articleJ Neurooncol · November 2012
Glioblastoma multiforme (GBM) is the most common and devastating form of primary central nervous system malignancy. The prognosis for patients diagnosed with GBM is poor, having a median survival rate of 12-15 months. Despite modern advances in the develop ...
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Journal articleProc Natl Acad Sci U S A · October 23, 2012
Myeloid/lymphoid or mixed-lineage leukemia (MLL)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription. MLL genes are frequently mutated in human cancers. Unlike MLL1, MLL2 (also know ...
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Journal articleBr J Cancer · October 23, 2012
BACKGROUND: Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among rec ...
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Journal articleNature · August 2, 2012
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogene ...
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Journal articleOncotarget · August 2012
Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protei ...
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Journal articleOncotarget · July 2012
Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequen ...
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Journal article · March 1, 2012
Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In ...
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Journal articleMol Cancer Res · February 2012
Glioblastoma is universally fatal because of its propensity for rapid recurrence due to highly migratory tumor cells. Unraveling the genomic complexity that underlies this migratory characteristic could provide therapeutic targets that would greatly comple ...
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Journal articlePLoS One · 2012
BACKGROUND: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy ...
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Journal articleNucl Med Biol · January 2012
INTRODUCTION: Malignant glioma remains a significant therapeutic challenge, and immunotherapeutics might be a beneficial approach for these patients. A monoclonal antibody (MAb) specific for multiple molecular targets could expand the treatable patient pop ...
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Journal articleHum Mutat · January 2012
Mutations in the chromatin remodeling gene ARID1A have recently been identified in the majority of ovarian clear cell carcinomas (OCCCs). To determine the prevalence of mutations in other tumor types, we evaluated 759 malignant neoplasms including those of ...
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Journal articlePLoS One · 2012
Dysregulation of Otx2 is a hallmark of the pediatric brain tumor medulloblastoma, yet its functional significance in the establishment of these tumors is unknown. Here we have sought to determine the functional consequences of Otx2 overexpression in the mo ...
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Journal articleClin Dev Immunol · 2012
Despite advances in conventional treatment modalities for malignant brain tumors-surgery, radiotherapy, and chemotherapy-the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic t ...
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Journal articleBlood · September 15, 2011
Lymphodepletion augments adoptive cell transfer during antitumor immunotherapy, producing dramatic clinical responses in patients with malignant melanoma. We report that the lymphopenia induced by the chemotherapeutic agent temozolomide (TMZ) enhances vacc ...
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Journal articleScience · September 9, 2011
Oligodendrogliomas are the second most common malignant brain tumor in adults and exhibit characteristic losses of chromosomes 1p and 19q. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven tumors. Among ot ...
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Journal articleNeurosurgery · September 2011
BACKGROUND: Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monito ...
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Journal articleScience · July 22, 2011
The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres and other genomic sites. Because inactivating mutations of these genes are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status of ...
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Journal articleInt J Cancer · July 1, 2011
Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high-grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display library. To obtain mut ...
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Journal articleExpert Opin Biol Ther · July 2011
INTRODUCTION: Although considerable evidence supports the hypothesis that T cells play a critical role in the immune response against cancer, the ability to mount and sustain tumor-specific cellular responses in vivo remains a challenge. A strategy that ha ...
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Journal articleClin Cancer Res · June 15, 2011
PURPOSE: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective. EXPERIMENTAL DESIGN: A total of 75 patients ...
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Journal articleRadiat Res · June 2011
High-dose ionizing radiation is an established risk factor for glioma, but it remains unknown whether moderate- and low-dose radiation increase glioma risk. In this analysis, we assessed the evidence that self-reported exposures to diagnostic ionizing radi ...
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Journal articleCancer Research · April 15, 2011
AbstractIn 20% – 30% of all glioblastomas (GBMs), the most common and deadly form of glioma, gene rearrangements in amplified epidermal growth factor receptor (EGFR) cause amplification of a highly oncogenic ...
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Journal articleJ Natl Compr Canc Netw · April 2011
Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth fa ...
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Journal articleToxins (Basel) · March 2011
Determining radiographic progression in primary malignant brain tumors has posed a significant challenge to the neuroncology community. Glioblastoma multiforme (GBM, WHO Grade IV) through its inherent heterogeneous enhancement, growth patterns, and irregul ...
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Journal articleNeuro Oncol · March 2011
Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic c ...
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Journal articleToxins (Basel) · March 2011
Drug delivery of immunotoxins to brain tumors circumventing the blood brain barrier is a significant challenge. Convection-enhanced delivery (CED) circumvents the blood brain barrier through direct intracerebral application using a hydrostatic pressure gra ...
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Journal articleJ Biomed Opt · March 2011
We report the development of a compact point-detection fluorescence spectroscopy system and two data analysis methods to quantify the intrinsic fluorescence redox ratio and diagnose brain cancer in an orthotopic brain tumor rat model. Our system employs on ...
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Journal articleProc Natl Acad Sci U S A · February 22, 2011
Point mutations of the NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream e ...
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Journal articlePLoS One · February 4, 2011
BACKGROUND: Gliomas frequently contain mutations in the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase (IDH1) or the mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2). Several different amino acid substitutions recur at either IDH1 R1 ...
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Journal articleCancer Epidemiol Biomarkers Prev · February 2011
BACKGROUND: Allergies have been associated with decreased risk of glioma; but, associations between duration and timing of allergies, and antihistamine use and glioma risk have been less consistent. The objective was to investigate this association by anal ...
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Journal articleAnticancer Agents Med Chem · February 2011
Despite intensive efforts to improve multimodal treatment of brain tumor, survival remains limited. Current therapy consists of a combination of surgery, irradiation and chemotherapy with predisposition to long-term complications. Identifying novel targete ...
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Journal articleScience · January 28, 2011
Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and micro ...
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Journal articlePLoS One · January 26, 2011
Current radiographic response criteria for brain tumors have difficulty describing changes surrounding postoperative resection cavities. Volumetric techniques may offer improved assessment, however usually are time-consuming, subjective and require expert ...
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Journal articleJ Neurooncol · January 2011
Sorafenib, an oral VEGFR-2, Raf, PDGFR, c-KIT and Flt-3 inhibitor, is active against renal cell and hepatocellular carcinomas, and has recently demonstrated promising activity for lung and breast cancers. In addition, various protracted temozolomide dosing ...
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Journal articleBMC Dev Biol · November 18, 2010
BACKGROUND: Ganglioside biosynthesis occurs through a multi-enzymatic pathway which at the lactosylceramide step is branched into several biosynthetic series. Lc3 synthase utilizes a variety of galactose-terminated glycolipids as acceptors by establishing ...
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Journal articleJ Clin Oncol · November 1, 2010
PURPOSE: Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed ...
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Journal articleJ Biomed Res · November 2010
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults. Current therapy includes surgery, radiation and chemotherapy with temozolomide (TMZ). Major determinants of clinical response to TMZ include methylation status of the O6-me ...
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Journal articleNucl Med Biol · October 2010
INTRODUCTION: Monoclonal antibody (mAb) L8A4 binds specifically to the epidermal growth factor receptor variant III (EGFRvIII) that is present on gliomas but not on normal tissues, and is internalized rapidly after receptor binding. Because of the short ra ...
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Journal articleNucl Med Biol · October 2010
INTRODUCTION: Podoplanin/aggrus is a mucin-like sialoglycoprotein that is highly expressed in malignant gliomas. Podoplanin has been reported to be a novel marker to enrich tumor-initiating cells, which are thought to resist conventional therapies and to b ...
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Journal articleOncogene · September 16, 2010
Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered ...
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Journal articleBMC Cancer · September 1, 2010
BACKGROUND: Glioblastoma multiforme (GBM) is refractory to conventional therapies. To overcome the problem of heterogeneity, more brain tumor markers are required for prognosis and targeted therapy. We have identified and validated a promising molecular th ...
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Journal articleNeuro Oncol · September 2010
Glioblastoma multiforme (GBM) is one of the deadliest tumors afflicting humans, and the mechanisms of its onset and progression remain largely undefined. Our attempts to elucidate its molecular pathogenesis through DNA copy-number analysis by genome-wide d ...
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Journal articleInt J Cancer · August 1, 2010
Multidrug resistance protein 3 (MRP3), a multidrug resistance protein identified by serial analysis of gene expression as a glioblastoma multiforme (GBM)-associated molecule, is highly expressed in GBM, but not in normal brain cells. Thus, MRP3 is a candid ...
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Journal articleOncotarget · August 2010
The glioblastoma genome displays remarkable chromosomal aberrations, which harbor critical glioblastoma-specific genes contributing to several oncogenetic pathways. To identify glioblastoma-targeted genes, we completed a multifaceted genome-wide analysis t ...
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Journal articleBiochem Biophys Res Commun · July 30, 2010
Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+to NADPH). IDH1/2 were recently identified as mutated in a ...
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Journal articleJ Neurooncol · May 2010
A major obstacle in glioblastoma (GBM) therapy is the restrictive nature of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) is a novel method of drug administration which allows direct parenchymal infusion of therapeutics, bypassing the B ...
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Journal articleCancer Research · April 15, 2010
AbstractInterleukin-2 Receptor α (IL-2R α / CD25)-specific Antibodies Eliminate Regulatory T-cells (TRegs) and enhance Tumor-specific Immune ResponsesDuke University Medical ...
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Journal articleNeoplasia · January 2010
Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution s ...
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Journal articleBiochem Biophys Res Commun · January 1, 2010
The lacto-series gangliosides 3'-isoLM1 and 3',6'-isoLD1 have been identified as tumor-associated antigens whose formation is initiated by the Lc3-synthase. Until now, high-affinity IgG monoclonal antibodies (mAbs) against 3'-isoLM1 and 3',6'-isoLD1, which ...
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Journal articleCancer Res · January 1, 2010
OTX2 is a developmentally regulated transcription factor involved in early morphogenesis of the central nervous system. This gene is amplified and overexpressed in medulloblastoma cell lines, but the nature and extent of its genetic alterations in primary ...
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Journal articleCancer Biomark · 2010
Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In ...
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Journal articleBiochem Biophys Res Commun · December 18, 2009
IDH1 (isocitrate dehydrogenase 1) mutations have been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas as well as secondary glioblastomas. In contrast, primary glioblastomas very rarely contain ...
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Journal articleCancer Res · December 15, 2009
Mutations of the isocitrate dehydrogenase (IDH) metabolic enzymes IDH1 and IDH2 have been found to be frequent and early genetic alterations in astrocytomas and oligodendrogliomas. All mutations identified to date affect a single amino acid located within ...
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Journal articleBr J Cancer · December 15, 2009
BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 ...
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Journal articleHybridoma (Larchmt) · December 2009
Somatostatin receptor 2 (SSTR2) is expressed by most medulloblastomas (MEDs). We isolated monoclonal antibodies (MAbs) to the 12-mer (33)QTEPYYDLTSNA(44), which resides in the extracellular domain of the SSTR2 amino terminus, screened the peptide-bound MAb ...
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Journal articleCancer Res · December 1, 2009
Glioblastoma multiforme is the most prevalent type of adult brain tumor and one of the deadliest tumors known to mankind. The genetic understanding of glioblastoma multiforme is, however, limited, and the molecular mechanisms that facilitate glioblastoma m ...
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Journal articleCancer Sci · October 2009
Chaperone proteins and heat shock proteins (HSP) are essential components of cellular protein folding systems under normal conditions; their expression and activities are upregulated during stress. Chronically stressed tumors frequently exhibit high chaper ...
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Journal articleCancer Chemother Pharmacol · October 2009
PURPOSE: Sphingosine kinase is an oncogene that is up-regulated in several solid tumors. The product of the sphingosine kinase activity, sphingosine-1-phosphate is a potent mitogen involved in diverse cell processes such as cell survival and migration. Cur ...
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Journal articleBrain Pathol · October 2009
Given the highly infiltrative growth pattern of malignant glioma and the lack of specificity associated with currently available treatment regimens, alternative strategies designed to eradicate cancer cells while limiting collateral toxicity in normal tiss ...
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Journal articleMol Cancer Ther · October 2009
Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise ...
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Journal articleNeuro Oncol · October 2009
This phase I clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG) was designed to determine the maximum tolerated dose (MTD) and toxicity of three different 5-day dosing regimens of temozolomide (TMZ) in combination ...
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Journal articleCancer · August 1, 2009
BACKGROUND: Glioblastoma multiforme (GBM), the most lethal type of brain tumor, has a 1-year median survival. The effect of carmustine wafers on the survival of newly diagnosed GBM patients treated with radiotherapy (RT) and concurrent temozolomide (TMZ) p ...
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Journal articleExpert Opin Investig Drugs · August 2009
Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art ...
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Journal articleNucl Med Biol · August 2009
INTRODUCTION: Carcinomatous meningitis (CM) is a devastating disease characterized by the dissemination of malignant tumor cells into the subarachnoid space along the brain and spine. Systemic treatment with monoclonal antibody (mAb) trastuzumab can be eff ...
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Journal articleCancer Res · July 15, 2009
There is widespread agreement that cancer gene discovery requires high-quality tumor samples. However, whether primary tumors or cultured samples are superior for cancer genomics has been a longstanding subject of debate. This debate has recently become mo ...
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Journal articleJ Biol Chem · June 19, 2009
Epidermal growth factor receptor (EGFR) gene amplification, mutations, and/or aberrant activation are frequent abnormalities in malignant gliomas and other human cancers and have been associated with an aggressive clinical course and a poor therapeutic out ...
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Journal articleExpert Opin Ther Targets · June 2009
Glioblastoma is the commonest primary brain tumor, as well as the deadliest. Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements ...
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Journal articleMol Pharmacol · June 2009
The presence of DNA damage initiates signaling through the ataxia-telangiectasia mutated kinase (ATM) and the ATM- and the Rad3-related kinase (ATR), which phosphorylate, thus activating, the checkpoint kinases (Chk) 1 and 2, which leads to cell cycle arre ...
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Journal articleJ Clin Oncol · May 20, 2009
2034 Background: TRegs are increased in patients with GBM and constitutively express the high affinity interleukin-2 receptor (IL-2Rα). Treatment with an antibody that blocks IL-2Rα signaling functionally inactivates and eliminates TRegs without inducing a ...
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Journal articleJ Clin Oncol · May 20, 2009
2021 Background: Unlike conventional therapies for GBM, immunologic targeting of tumor-specific gene mutations allows precise eradication of neoplastic cells with reduced toxicity. EGFRvIII is a constitutively activated and immunogenic mutation not express ...
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Journal articleJ Clin Oncol · May 20, 2009
e13016 Background: Recurrent malignant gliomas have a poor prognosis, with a median survival of 6-15 months, with grade 4 glioblastomas more aggressive than grade 3 anaplastic astrocytomas or oligodendrogliomas. Vascular endothelial growth factor (VEGF) an ...
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Journal articleJ Clin Oncol · May 20, 2009
e13025 Background: GBMs are vascular tumors and inherently resistant to therapy. The prognosis for patients is poor with a median survival of 9-15 months. Patients with unresectable or multifocal GBMs have an even poorer prognosis, with a median survival o ...
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Journal articleBMC Med Genomics · May 8, 2009
BACKGROUND: Microorganisms have been associated with many types of human diseases; however, a significant number of clinically important microbial pathogens remain to be discovered. METHODS: We have developed a genome-wide approach, called Digital Karyotyp ...
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Journal articleFASEB J · May 2009
Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30-100 nm membranous vesicles released from ma ...
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Journal articleClin Med Oncol · April 8, 2009
In the adult population, glioblastoma multiforme is one of the most common primary brain tumors encountered. Unfortunately, this highly malignant tumor represents over 50% of all types of primary central nervous system gliomas. The vast majority of GBMs de ...
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Journal articleCancer Epidemiol Biomarkers Prev · April 2009
Because glioma etiology is largely unknown, the inverse association of glioma risk with atopic conditions is promising and deserves close scrutiny. We examined the association between a history of allergies, asthma, and eczema, and glioma risk using siblin ...
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Journal articleNat Genet · April 2009
We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppress ...
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Journal articleJ Clin Oncol · March 10, 2009
PURPOSE: This phase II trial was designed to define the role of O(6)-benzylguanine (O(6)-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administerin ...
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Journal articleCancer Chemother Pharmacol · March 2009
PURPOSE: Resistance of neoplastic cells to the alkylating drug BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] has been correlated with expression of O (6)-methylguanine-DNA methyltransferase, which repairs the O (6)-chloroethylguanine produced by the drug. Ot ...
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Journal articleJ Toxicol Environ Health B Crit Rev · March 2009
This review is based on the proceedings from the Second Lebow Conference, held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the pot ...
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Journal articleN Engl J Med · February 19, 2009
BACKGROUND: A recent genomewide mutational analysis of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that wer ...
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Journal articleBiol Chem · February 2009
Epidermal growth factor receptor variant III (EGFRvIII) is a glycoprotein uniquely expressed in glioblastoma, but not in normal brain tissues. To develop targeted therapies for brain tumors, we selected RNA aptamers against the histidine-tagged EGFRvIII ec ...
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Journal articleClin Cancer Res · February 1, 2009
PURPOSE: This phase II trial was designed to define the efficacy of Gliadel wafers in combination with an infusion of O6-benzylguanine (O6-BG) that suppresses tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in patients with recurrent glioblastoma m ...
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Journal articleCancer Res · December 15, 2008
An additional tumor suppressor gene on chromosome 9p telomeric to the CDKN2A/B locus has long been postulated to exist. Using Affymetrix 250K single nucleotide polymorphism arrays to screen for copy number changes in glioblastoma multiforme (GBM), we detec ...
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Journal articleJ Immunol Methods · November 30, 2008
The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in glioblastoma multiforme (GBM) and other neoplasms. As such it represents a truly tumor-specific target for antitumor immunothera ...
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Journal articleClin Cancer Res · November 1, 2008
PURPOSE: Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial ...
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Journal articleNature · October 23, 2008
Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dim ...
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Journal articleSemin Immunol · October 2008
Conventional therapies for malignant gliomas (MGs) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by non-specific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise erad ...
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Journal articleScience · September 26, 2008
Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleot ...
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Journal articleClin Cancer Res · August 1, 2008
PURPOSE: A major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temo ...
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Journal articleNeuro Oncol · June 2008
The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brai ...
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Journal articleCurr Cancer Drug Targets · May 2008
The total expression profiles of two medulloblastoma cell lines resistant to the preactivated form of cyclophosphamide (4-hydroperoxycyclophosphamide, 4-HC) were examined using the Affymetrix GeneChip U133A array. Our primary objective was to look for poss ...
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Journal articleExpert Rev Anticancer Ther · May 2008
Angiogenesis, the growth of new blood vessels from previously existing vasculature, is a requirement for tumor growth and metastasis. The first US FDA-approved drugs targeting angiogenesis have shown potential in the treatment of malignant gliomas. Immunot ...
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Journal articleCancer Res · April 15, 2008
Genomic alterations leading to aberrant activation of cyclin/cyclin-dependent kinase (cdk) complexes drive the pathogenesis of many common human tumor types. In the case of glioblastoma multiforme (GBM), these alterations are most commonly due to homozygou ...
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Journal articleNeuro Oncol · April 2008
The purpose of this study was to determine the feasibility and assess the efficacy and toxicity, among newly diagnosed malignant glioma patients, of administering (131)I-labeled murine antitenascin monoclonal antibody 81C6 ((131)I-81C6) into a surgically c ...
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Journal articleNeuro Oncol · February 2008
Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemotherapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Alt ...
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Journal articleJ Neurosurg · February 2008
OBJECT: Diffusely infiltrating astrocytomas are the most common primary brain tumors. As a group, they demonstrate an inherent tendency toward malignant progression. Histological grading using the guidelines of the World Health Organization (WHO) remains t ...
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Journal articleClin Cancer Res · January 15, 2008
PURPOSE: Epidermal growth factor receptor variant III (EGFRvIII) is an oncogenic, constitutively active mutant form of the EGFR that is commonly expressed in glioblastoma and is also detected in a number of epithelial cancers. EGFRvIII presents a unique an ...
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Journal articleCancer Immunol Immunother · January 2008
PURPOSE: Immunotoxins as anti-cancer therapeutics have several potential advantages over conventional agents including a high specificity, extraordinary potency, and a lack of an identified mechanism for resistance. It has been clearly demonstrated that Ps ...
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Journal articleJ Nucl Med · January 2008
UNLABELLED: alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of th ...
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Journal articleCancer Chemother Pharmacol · November 2007
PURPOSE: The DNA repair protein, O (6)-alkylguanine-DNA alkyltransferase (AGT), is a primary source of tumor resistance to agents such as temozolomide and chloroethylnitrosoureas that form DNA lesions at the O (6)-position of guanines. To increase the effi ...
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Journal articleJ Clin Oncol · October 20, 2007
PURPOSE: The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irin ...
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Journal articleJ Neurosci · October 17, 2007
The heat shock response is a highly conserved "stress response" mechanism used by cells to protect themselves from potentially damaging insults. It often involves the upregulated expression of chaperone and heat shock proteins (HSPs) to prevent damage and ...
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Journal articleNucl Med Biol · October 2007
An attractive feature of targeted radionuclide therapy is the ability to select radionuclides and targeting vehicles with characteristics that are best suited for a particular clinical application. One combination that has been receiving increasing attenti ...
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Journal articleMol Cancer Ther · September 2007
Monotherapies have proven largely ineffective for the treatment of glioblastomas, suggesting that increased patient benefit may be achieved by combining therapies. Two protumorigenic pathways known to be active in glioblastoma include RAS/RAF/mitogen-activ ...
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Journal articleNeuro Oncol · July 2007
VNP40101M, or 1,2-bis(methylsulfonyl)-1-(2-choloroethyl)-2-(methylamino)carbonylhydrazine (Cloretazine), is a bifunctional prodrug that belongs to a class of DNA-modifying agents-the sulfonylhydrazines-that has been synthesized and been shown to have activ ...
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Journal articleNeuro Oncol · July 2007
Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that ...
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Journal articleOncogene · June 14, 2007
Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in several solid cancers, including malignant gliomas, upon adoption of metastatic or invasive behaviors. SPARC expression in glioma cells promotes invasion and ...
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Journal articleMol Carcinog · June 2007
Glioblastomas are highly lethal cancers that resist current therapies. Novel therapies under development target molecular mechanisms that promote glioblastoma growth. In glioblastoma patient specimens, the non-receptor tyrosine kinase focal adhesion kinase ...
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Journal articleNucl Med Biol · May 2007
INTRODUCTION: The neurohistological findings in patients treated with targeted beta emitters such as (131)I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting ...
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Journal articleExpert Rev Anticancer Ther · May 2007
Adults with primary malignant glioma have an unacceptably poor outcome. Most of these tumors recur at or adjacent to the site of origin, which indicates that failure to eradicate local tumor growth is a major factor contributing to poor outcome. Therefore, ...
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Journal articleClin Cancer Res · April 1, 2007
PURPOSE: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4(+) T cell numbers and function. We have previously shown that increased regulatory T cell (T(reg)) fractions in these p ...
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Journal articlePsychooncology · March 2007
The purpose of the present study was to examine the demographic, medical, and social cognitive determinants of exercise intentions in a institution-based cohort of primary brain tumor patients. Using a cross-sectional survey, 100 primary brain tumor patien ...
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Journal articleClin Cancer Res · February 15, 2007
PURPOSE: Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy. This study was conducted to determine if the combination of a novel antiangiogenic therapy, bevacizuma ...
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Journal articleNeurosurgery · February 2007
OBJECTIVE: Convection-enhanced delivery (CED) holds tremendous potential for drug delivery to the brain. However, little is known about the volume of distribution achieved within human brain tissue or how target anatomy and catheter positioning influence d ...
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Journal articleNucl Med Biol · February 2007
INTRODUCTION: When labeled with iodine-131, the antitenascin monoclonal antibody (mAb) 81C6 has shown promise as a targeted radiotherapeutic in patients with brain tumors. Because of its more favorable gamma-ray properties, lutetium-177 might be a better l ...
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Journal articleNeuro Oncol · January 2007
Cloretazine (VNP40101M) is a newly synthesized alkylating agent belonging to a novel class of alkylating agents called 1,2-bis(sulfonyl)hydrazines. Agents that belong to this class do not produce vinylating and chloroethylating species, and hence this clas ...
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Journal articleSupport Care Cancer · January 2007
GOALS OF THE WORK: The purpose of the present investigation was to examine the interest and exercise preferences of an institution-based sample of brain tumor patients. Secondary aims were to examine potential differences in participant's interest and pref ...
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Journal articleNature · December 7, 2006
Ionizing radiation represents the most effective therapy for glioblastoma (World Health Organization grade IV glioma), one of the most lethal human malignancies, but radiotherapy remains only palliative because of radioresistance. The mechanisms underlying ...
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Journal articleMol Cancer Ther · October 2006
Promoter hypermethylation of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to co ...
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Journal articleClin Cancer Res · September 1, 2006
PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinoma (HNSCC) where expression levels correlate with decreased survival. Therapies that block EGFR have shown limited efficacy in clinical trials and prima ...
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Journal articleCancer Res · September 1, 2006
Malignant gliomas are highly proliferative and angiogenic cancers resistant to conventional therapies. Although RAS and RAF mutations are uncommon in gliomas, RAS activity is increased in gliomas. Additionally, vascular endothelial growth factor and its co ...
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Journal articleCancer Res · August 15, 2006
Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical tumor subpopulations within gliomas share characteristics with neural stem cells. We examined the potential of stem cell-like glioma cells (SCLGC) to support tumor angiogenesis ...
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Journal articleClin Cancer Res · July 15, 2006
PURPOSE: Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and eva ...
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Journal articleJ Clin Oncol · June 20, 2006
11505 Background: Glioblastomas are highly lethal cancers that resist current therapies. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase overexpressed in glioblastoma patient specimens that may promote glioma growth and invasion by increasing ...
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Journal articleJ Clin Oncol · June 20, 2006
2529 Background: Despite multimodality approaches, survival with GBM is dismal. Induction of immune responses to suppress the infiltrative, residual component with an easily manufactured and administered immunotherapy has been a theoretical ideal. The epid ...
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Journal articleJ Nucl Med · June 2006
UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine ...
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Journal articleCancer · May 15, 2006
BACKGROUND: Exercise may represent a supportive intervention that may complement existing neurooncologic therapies and address a multitude of therapy-induced debilitating side effects in patients with brain tumors. Given the limited evidence, the authors c ...
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Journal articleExpert Rev Anticancer Ther · May 2006
Tumors of the CNS frequently have devastating consequences in terms of cognitive and motor function, personality and mortality. Despite decades of work, current therapies have done little to alter the course of these deadly diseases. The discovery that cha ...
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Journal articleNeurosurg Focus · April 15, 2006
OBJECTIVES: Convection-enhanced delivery (CED) is a novel technique used to deliver agents to the brain parenchyma for treatment of neoplastic, infectious, and degenerative conditions. The purpose of this study was to determine if CED would provide a large ...
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Journal articleClin Cancer Res · April 1, 2006
PURPOSE: More brain tumor markers are required for prognosis and targeted therapy. We have identified and validated promising molecular therapeutic glioblastoma multiforme (GBM) targets: human transmembrane glycoprotein nonmetastatic melanoma protein B (GP ...
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Journal articleCancer Res · March 15, 2006
Immunosuppression is frequently associated with malignancy and is particularly severe in patients with malignant glioma. Anergy and counterproductive shifts toward T(H)2 cytokine production are long-recognized T-cell defects in these patients whose etiolog ...
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Journal articleJ Clin Oncol · March 10, 2006
Malignant gliomas, including the most common subtype, glioblastoma multiforme (GBM), are among the most devastating of neoplasms. Their aggressive infiltration in the CNS typically produces progressive and profound disability--ultimately leading to death i ...
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Journal articleClin Cancer Res · February 1, 2006
PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among pat ...
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Journal articleJ Clin Oncol · January 1, 2006
PURPOSE: To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients. PATIENTS AND METHODS: In this phase II trial, 100 mCi of 131I ...
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Journal articleNucl Med Biol · January 2006
INTRODUCTION: MR1-1 is a single-chain Fv (scFv) fragment that binds with high affinity to epidermal growth factor receptor variant III, which is overexpressed on gliomas and other tumors but is not present on normal tissues. The objective of this study was ...
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Journal articleBioconjug Chem · 2006
Novel methods are needed for the radiohalogenation of cell-internalizing proteins and peptides because rapid loss of label occurs after lysosomal processing when these molecules are labeled using conventional radioiodination methodologies. We have develope ...
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Journal articleInt J Occup Environ Health · 2006
The initiation of brain tumors has been demonstrated in animals exposed to industrial chemicals, results which have not been demonstrated in humans. This report describes the National Occupation Exposure Survey conducted by the National Institute of Occupa ...
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Journal articleCancer Res · December 15, 2005
In normal epithelial tissues, the multifunctional cytokine transforming growth factor-beta (TGF-beta) acts as a tumor suppressor through growth inhibition and induction of differentiation whereas in advanced cancers, TGF-beta promotes tumor progression thr ...
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Journal articleCancer Chemother Pharmacol · December 2005
Substance P receptor (SPR), a G protein-coupled receptor (GPCR), is found in human glioblastomas, and has been implicated in their growth. Consistent with a role for SPR in cell growth, activation of SPR in U373 MG human glioblastoma cells leads to the pho ...
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Journal articleClin Cancer Res · November 15, 2005
PURPOSE: Primary central nervous system (CNS) tumors represent a diverse group of tumor types with heterogeneous molecular mechanisms that underlie their formation and maintenance. CNS tumors depend on angiogenesis and often display increased activity of E ...
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Journal articleCancer · October 15, 2005
BACKGROUND: Allelic losses of 1p and 19q arms correlate with the oligodendroglial phenotype as well as with sensitivity to radiotherapy and chemotherapy. Furthermore, the DNA repair gene, methylguanine methyltransferase (MGMT), is diminished in 80% of olig ...
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Journal articleNeuro Oncol · October 2005
We present guidelines to standardize the reporting of phase 1 and phase 2 neuro-oncology trials. The guidelines are also intended to assist with accurate interpretation of results from these trials, to facilitate the peer-review process, and to expedite th ...
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Journal articleLeuk Lymphoma · October 2005
This study investigated stromal changes in expression of tenascin and vasculogenesis in lymphoma. Documenting the dynamic nature of the stromal changes in lymphoma in relation to response to therapy is helpful in planning new therapies directed at these ta ...
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Journal articleJ Clin Oncol · October 1, 2005
PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The ...
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Journal articleMol Cancer Ther · September 2005
Temozolomide is a DNA-methylating agent used in the treatment of malignant gliomas. In this study, we have examined if inhibition of poly(ADP-ribose) polymerase (PARP) could increase the cytotoxicity of temozolomide, particularly in cells deficient in DNA ...
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Journal articleFront Biosci · September 1, 2005
Glial neoplasms represent 0.5-1% of all cancers in most Western countries. Malignant gliomas are among the most devastating cancers, leading to death in most cases. They present unique challenges due to their location, aggressive biological behavior and di ...
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Journal articleNeuro Oncol · July 2005
Chaperone proteins are most notable for the proteo- and cyotoprotective capacities they afford during cellular stress. Under conditions of cellular normalcy, chaperones still play integral roles in the folding of nascent polypeptides into functional entiti ...
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Journal articleJ Nucl Med · June 2005
UNLABELLED: The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into su ...
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Journal articleCancer Res · May 15, 2005
Despite the strikingly grave prognosis for older patients with glioblastomas, significant variability in patient outcome is experienced. To explore the potential for developing improved prognostic capabilities based on the elucidation of potential biologic ...
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Journal articleCancer Res · February 1, 2005
Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93 ...
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Journal articleNeuro Oncol · January 2005
Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to tra ...
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Journal articleMol Cancer Ther · January 2005
Malignant gliomas are highly lethal tumors that display striking genetic heterogeneity. Novel therapies that inhibit a single molecular target may slow tumor progression, but tumors are likely not dependent on a signal transduction pathway. Rather, maligna ...
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Journal articleLung Cancer · January 2005
PURPOSE: Extracellular matrix (ECM) proteins play a significant role in the survival and metastasis of cancer cells. Tenascin-C (TN-C) is an extracellular matrix protein and its large isoform has been implicated in tumor progression. Goal of this study was ...
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Journal articleJ Biol Chem · December 10, 2004
Secreted protein acidic, rich in cysteine (SPARC), is an extracellular matrix protein expressed in many advanced cancers, including malignant gliomas. We and others have previously shown that human glioma cell lines engineered to overexpress SPARC adopt an ...
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Journal articleJ Immunol · November 15, 2004
Mutated epidermal growth factor receptor (EGF-RvIII, DeltaEGF-R, and de2-7 EGF-R) is the result of an 801-bp deletion within the extracellular domain of wild-type EGF-R and is expressed by breast carcinomas, but not by normal breast tissues. EGF-RvIII is e ...
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Journal articleNucl Med Biol · October 2004
Monoclonal antibodies such as L8A4, reactive with the epidermal growth factor receptor variant III, internalize after receptor binding resulting in proteolytic degradation by lysosomes. Labeling internalizing mAbs requires the use of methodologies that res ...
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Journal articleExpert Opin Biol Ther · September 2004
Conventional treatment of brain tumours includes surgical, radiotherapeutic and chemotherapeutic modalities. Nonetheless, the outcome of patients with brain tumours, in particular glioblastoma, remains poor. Immunotherapy with armed or unarmed monoclonal a ...
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Journal articleMol Cancer Ther · September 2004
The chemotherapeutic activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU or carmustine) may be improved by the addition of O6-benzylguanine (O6-BG). The reaction of O6-BG with O6-alkylguanine-DNA alkyltransferase (AGT) prevents the repair of O6-chloroet ...
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Journal articleBlood · August 1, 2004
We report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of (131)I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered acti ...
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Journal articleCancer Res · August 1, 2004
The phosphatidylinositol 3'-kinase pathway is activated in multiple advanced cancers, including glioblastomas, through inactivation of the PTEN tumor suppressor gene. Recently, mutations in PIK3CA, a member of the family of phosphatidylinositol 3'-kinase c ...
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Journal articleJ Mol Diagn · August 2004
Astrocytoma is comprised of a group of common intracranial neoplasms that are classified into four grades based on the World Health Organization histological criteria and patient survival. To date, histological grade, patient age, and clinical performance, ...
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Journal articleJ Clin Oncol · July 15, 2004
1555 Background: Erlotinib HCL (Tarceva), an orally active, highly potent and selective inhibitor of the epidermal growth factor receptor (HER1/EGFR), has documented clinical activity in glioblastoma multiforme (GBM) (M Prados ASCO 02). GBM is an interesti ...
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Journal articleJ Clin Oncol · July 15, 2004
1569 Background: In a prior phase I study we established the dose of 100mCi as the maximum tolerated dose of iodine 131-labeled murine anti-tenascin antibody 81C6 (131I-81C6) injected into a surgically created resection cavity (SCRC) for the treatment of r ...
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Journal articleNeuro Oncol · July 2004
Cell adhesion molecules of the immunoglobulin superfamily are aberrantly expressed in malignant glioma. Amongst these, the human poliovirus receptor CD155 provides a molecular target for therapeutic intervention with oncolytic poliovirus recombinants. Poli ...
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Journal articleMol Cancer Ther · June 2004
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that promotes malignant glioma invasion, angiogenesis, and immunosuppression. Antisense oligonucleotide suppression of TGF-beta(2) ligand expression has shown promise in preclinical a ...
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Journal articleClin Cancer Res · May 1, 2004
PURPOSE: We have reported previously that tumors expressing wild-type epidermal growth factor receptor (EGFR) in a murine model are sensitive to the EGFR tyrosine kinase inhibitor gefitinib, whereas tumors expressing mutant EGFR variant III (EGFRvIII) are ...
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Journal articleNucl Med Biol · April 2004
We have obtained encouraging responses in recent Phase I studies evaluating (131)I-labeled human/murine chimeric 81C6 anti-tenascin monoclonal antibody (ch81C6) administered into surgically-created tumor resection cavities in brain tumor patients. However, ...
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Journal articleNeuro Oncol · April 2004
Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or prog ...
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Journal articleNeuro Oncol · April 2004
In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administere ...
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Journal articleNeuroepidemiology · 2004
High-quality cancer registry data are essential for assessing trends in incidence rates. This study evaluated the consistency of brain tumor surveillance data using a random sample of cases from the Connecticut Tumor Registry. Three neuropathologists indep ...
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Journal articleJ Clin Oncol · January 1, 2004
PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an op ...
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Journal articleClin Cancer Res · November 15, 2003
PURPOSE: The monoclonal antibody (MAb) trastuzumab (Herceptin) effectively treats HER2-overexpressing extracerebral breast neoplasms. Delivery of such macromolecule therapeutic agents to intracerebral metastases, however, is limited by the tight junctions ...
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Journal articleJ Neurooncol · October 2003
TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maxim ...
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Journal articleClin Cancer Res · September 15, 2003
PURPOSE: The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse ...
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Journal articleJ Biol Chem · May 2, 2003
We employed a genetically defined human cancer model to investigate the contributions of two genes up-regulated in several cancers to phenotypic changes associated with late stages of tumorigenesis. Specifically, tumor cells expressing two structurally unr ...
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Journal articleNucl Med Biol · May 2003
The objective of this study was to develop a method for labeling internalizing monoclonal antibodies (mAbs) such as those reactive to the anti-epidermal growth factor receptor variant III (EGFRvIII) with the alpha-particle emitting radionuclide (211)At. Ba ...
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Journal articleJ Clin Oncol · February 15, 2003
PURPOSE: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studi ...
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Journal articleJ Neurooncol · 2003
Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific t ...
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Journal articleInt J Radiat Oncol Biol Phys · November 15, 2002
PURPOSE: To establish the theoretical framework and study the feasibility of (211)At-labeled anti-tenascin chimeric 81C6 monoclonal antibody (mAb) as anti-vascular endoradiotherapy for the treatment of glioblastoma multiforme (GBM) tumors. METHODS AND MATE ...
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Journal articleClin Cancer Res · November 2002
Iressa (ZD1839) is a p.o.-active, selective, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways implicated in cancer cell proliferation, survival, and host-dependent processes promoting cancer gro ...
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Journal articleMol Biol Rep · September 2002
ADAM family plays important roles in neurogenesis. The cytoplasmic tail of ADAM19 (ADAM19-CT) contains 193 residues. The presence of two putative SH3 ligand-binding sites suggests potential interactions with cytosolic proteins, which could be possibly link ...
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Journal articleMol Cancer Ther · September 2002
We have previously demonstrated (A. E. Pegg, Cancer Res., 50: 6119-6129, 1990) that O6-benzylguanine (O6-BG) enhances nitrosourea, temozolomide, and cyclophosphamide activity in malignant glioma xenografts growing in athymic nude mice. More recently, we ha ...
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Journal articleMol Cancer Ther · July 2002
Medulloblastoma (D-341 MED) and rhabdomyosarcoma (TE-671) cell lines, which are resistant to either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or the combination of BCNU and O6-benzylguanine (O6-BG), were generated by serial escalation of BCNU. The activi ...
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Journal articleNature · June 27, 2002
Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis si ...
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Journal articleCancer · May 15, 2002
BACKGROUND: Astrocytoma is a primary brain tumor that affects 20,000 Americans each year. To date, only age and histologic grade stand out as independent predictors of survival. There is now increased interest in the use of molecular markers as objective s ...
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Journal articleJ Clin Oncol · May 1, 2002
PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O(6)-alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent ...
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Journal articleNeuro Oncol · April 2002
Cell lines and xenografts derived from medulloblastomas are useful tools to investigate the chromosomal changes in these tumors. Here we used G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridiz ...
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Journal articleJ Clin Oncol · March 1, 2002
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PURPOSE: To assess the efficacy and toxicity of intraresection cavity (131)I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase ...
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Journal articleCancer Immunol Immunother · February 2002
The use of anti-idiotype (anti-id) vaccines for immunotherapy of human cancers is attractive, as immunization with true anti-id reagents (Ab2 beta) has been shown to induce both cellular and humoral immunity, frequently when the original antigen does not, ...
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Journal articleNeurosurgery · January 2002
OBJECTIVE: Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by D ...
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Journal articleNucl Med Biol · January 2002
Monoclonal antibodies (mAbs) such as the tumor-specific anti-epidermal growth factor receptor variant III (EGFRvIII) that are internalized and degraded after cell binding necessitate the use of radioiodination methods that minimize the loss of radioactivit ...
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Journal articleCancer Chemother Pharmacol · November 2001
PURPOSE: This study was conducted to define the activity of irofulven in the treatment of a series of xenografts derived from human glioblastoma multiforme growing subcutaneously and intracranially in athymic nude mice. METHODS: Athymic mice bearing subcut ...
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Journal articleNucl Med Biol · October 2001
Receptor-mediated internalization of monoclonal antibodies (mAbs), such as those specific for the epidermal growth factor receptor variant III (EGFRvIII), can lead to rapid loss of radioactivity from the target cell. In the current study, the anti-EGFRvIII ...
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Journal articleJ Nucl Med · October 2001
UNLABELLED: In vitro and in vivo studies in human glioma models suggest that the antitenascin monoclonal antibody 81C6 labeled with the 7.2-h-half-life alpha-particle emitter (211)At might be a valuable endoradiotherapeutic agent for the treatment of brain ...
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Journal articleCancer Chemother Pharmacol · September 2001
PURPOSE: The in vivo antitumor activity of a novel topoisomerase I inhibitor, J-107088, was tested in athymic nude mice bearing subcutaneous or intracranial pediatric and adult malignant CNS tumor-derived xenografts. METHODS: J-107088 was administered to a ...
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Journal articleCancer Chemother Pharmacol · July 2001
PURPOSE: Camptothecins have emerged as an important new class of antitumor drugs. Camptothecin derivatives such as CPT-11 and topotecan are commercially available and approved for the treatment of colorectal (CPT-11) and ovarian and small-cell lung cancer ...
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Journal articleCancer Res · May 1, 2001
Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will require a better understanding of the molecular nature of these tumors. We, therefore, mimicked the most common genetic changes found in grade III-IV gliomas, disruption of the ...
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Journal articleCancer · May 1, 2001
Even with novel chemotherapeutic agents and external beam radiation therapy, the prognosis of neoplastic meningitis secondary to malignant melanoma is still dismal. The authors report a case study of a 46-year-old white female who presented with progressiv ...
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Journal articleInt J Cancer · December 15, 2000
Combinatorial variation of CDR3 of V(H) and V(L), followed by phage display, was used to select affinity mutants of the parental anti-epidermal growth factor receptor-vIII (EGFRvIII) scFv MR1. One mutant, MR1-1(scFv), had increased specific binding affinit ...
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Journal articleJ Clin Oncol · November 15, 2000
PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any ob ...
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Journal articleJ Clin Oncol · October 15, 2000
PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O(6) position of guanine. O(6)-benzylguanine ...
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Journal articleClin Cancer Res · October 2000
Temozolomide, an imidazole tetrazinone, and CPT-11, a camptothecin derivative, have previously been shown to have anti-central nervous system tumor activity in laboratory and clinical studies. The current experiments were designed to evaluate the activity ...
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Journal articleClin Cancer Res · October 2000
Intracerebral microinfusion (ICM) is an innovative technique of delivering therapeutic agents throughout large portions of the brain that circumvents the blood-brain barrier, minimizes systemic toxicity, and provides a homogeneous distribution of the infus ...
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Journal articleGenome Res · September 2000
Genes expressed specifically in malignant tissue may have potential as therapeutic targets but have been difficult to locate for most cancers. The information hidden within certain public databases can reveal RNA transcripts specifically expressed in trans ...
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Journal articleBiochem Biophys Res Commun · August 28, 2000
EGFRvIII is the most common deletion variant of the epidermal growth factor receptor and is found in cancers of the brain, breast, ovary, and lung. The complete absence of the receptor in healthy tissues makes it an ideal tumor marker. We sought to design ...
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Journal articleCancer Res · August 15, 2000
The mutant epidermal growth factor receptor variant III (EGFRvIII) has been found on gliomas and other tumors but not on normal tissues, including those that express the wild-type receptor. Monoclonal antibodies (mAbs) specific for EGFRvIII are rapidly int ...
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Journal articleJ Histochem Cytochem · August 2000
Epidermal growth factor receptor (EGFR), its variant, EGFRvIII, and tenascin are glioma-associated antigens that are hyperexpressed by neoplastic glial cells relative to normal brain, making them attractive antigenic targets for immunotherapy. Preliminary ...
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Journal articleExpert Opinion on Therapeutic Targets · August 1, 2000
Optimal immunotherapeutic approaches to cancer cell eradication require the specific recognition of neoplastic cells and minimal destruction of bystander, normal cells. This is especially crucial within the CNS because of the infiltrative growth pattern of ...
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Journal articleClin Cancer Res · July 2000
Recombinant immunotoxins are fusion proteins composed of Fv regions of antibodies and bacterial or plant toxins that are being developed for the targeted therapy of cancer. MR1(Fv)-PE38 is a single-chain recombinant immunotoxin that targets a mutant form o ...
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Journal articleProc Natl Acad Sci U S A · June 20, 2000
The epidermal growth factor receptor (EGFR) is often amplified and rearranged structurally in tumors of the brain, breast, lung, and ovary. The most common mutation, EGFRvIII, is characterized by an in-frame deletion of 801 base pairs, resulting in the gen ...
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Journal articleActa Neuropathol · April 2000
Loss of portions of chromosome 17p, usually through the formation of i(17qp) is a well-known finding in medulloblastomas. Loss of heterozygosity (LOH) studies, however, occasionally demonstrate loss of the more distal portions of 17p, a pattern which is mo ...
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Journal articleInt J Radiat Oncol Biol Phys · March 1, 2000
PURPOSE: The objective of this study was to perform the dosimetry and evaluate the dose-response relationships in newly diagnosed patients with malignant brain tumors treated by direct injections of (131)I-labeled 81C6 monoclonal antibody (MAb) into surgic ...
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Journal articleJ Neuroimmunol · February 1, 2000
To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell line derived from an astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morp ...
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Journal articleCancer Chemother Pharmacol · 2000
PURPOSE: To evaluate the role of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus O6-benzylguanine (O6-BG) in the treatment of both Mer+ and Mer- tumors. METHODS: The effect of pretreatment with O6-BG on the activity of BCNU against Mer- human central nerv ...
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Journal articleCancer Chemother Pharmacol · 2000
PURPOSE: To further evaluate the activity of irinotecan (CPT-11) plus 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU) in the treatment of central nervous system tumor-derived xenografts in athymic nude mice. METHODS: We report studies evaluating the schedule-de ...
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Journal articleBrain Tumor Pathol · 2000
Cell surface receptors are attractive candidates for targeted therapy of cancer. Growth factors and their receptors play important roles in the regulation of cell division, development, and differentiation. Among those, the epidermal growth factor receptor ...
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Journal articleCancer Chemotherapy and Pharmacology · 2000
Purpose: To evaluate the role of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) plus O6-benzylguanine (O6-BG) in the treatment of both Mer+ and Mer- tumors. Methods: The effect of pretreatment with O6-BG on the activity of BCNU against Mer- human central nerv ...
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Journal articleJ Biol Chem · December 3, 1999
We sought to characterize the pathway by which the multifunctional cytokine transforming growth factor-beta (TGF-beta) inhibits the proliferation of normal astrocytes, and we analyzed the alterations in the TGF-beta pathway in human glioma cell lines. Upon ...
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Journal articleInt J Radiat Oncol Biol Phys · September 1, 1999
PURPOSE: The antitenascin human/mouse chimeric monoclonal antibody labeled with the alpha-particle-emitting radionuclide 211At is of interest as an endoradiotherapeutic agent for the treatment of brain tumors. To facilitate the investigation of 211At-label ...
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Journal articleClin Cancer Res · September 1999
The incidence of neoplastic meningitis is on the rise. Neoplastic meningitis can result from a direct seeding of the neuraxis by primary brain tumors or by hematogeneous spread of systemic solid tumors. A frequent genetic alteration in primary brain tumors ...
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Journal articleAm J Pathol · August 1999
Oligodendroglial neoplasms are a subgroup of gliomas with distinctive morphological characteristics. In the present study we have evaluated a series of these tumors to define their molecular profiles and to determine whether there is a relationship between ...
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Journal articleClin Cancer Res · June 1999
A single-chain antibody fragment, MR1(scFv), with specific binding to epidermal growth factor receptor-vIII (EGFRvIII), was produced, radiolabeled, and evaluated for biodistribution in human glioma-bearing athymic mice. The mutant receptor EGFRvIII has a d ...
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Journal articleNucl Med Biol · May 1999
Monoclonal antibodies (MAbs) such as the anti-epidermal growth factor variant III (EGFRvIII) MAb L8A4 are rapidly internalized, which can lead to rapid loss of radioactivity from the tumor cell. The aim of this study was to evaluate the potential utility o ...
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Journal articleCurr Opin Oncol · May 1999
De novo glioblastomas develop in older patients without prior clinical history of less malignant tumors. Progressive glioblastomas are common among younger patients and arise through progression from lower-grade astrocytomas. CDKN2A deletions, PTEN alterat ...
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Journal articleClin Cancer Res · May 1999
Neoplastic meningitis (NM) results from leptomeningeal dissemination of cancers arising within the central nervous system or metastasizing to the leptomeninges from systemic neoplasms. The inability to produce therapeutic drug levels intrathecally (i.t.) w ...
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Journal articleJ Clin Oncol · May 1999
PURPOSE: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma. PATIENTS AND METHODS: Patients w ...
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Journal articleJ Nucl Med · April 1999
UNLABELLED: The objective of this study was to perform the dosimetry of 131I-labeled 81C6 monoclonal antibody (MAb) in patients with recurrent malignant brain tumors, treated by direct injections of MAb into surgically created resection cavities (SCRCs). M ...
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Journal articleCancer Metastasis Rev · 1999
The development of immunotherapeutic protocols for the treatment of human CNS neoplasia over the past two decades has been impressive. Several crucial aspects have been defined, characterized, and in many cases, optimized (Wikstrand CJ, Zalutsky MR, Bigner ...
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Journal articleCancer Chemother Pharmacol · 1999
PURPOSE: The human medulloblastoma cell line D283 Med (4-HCR), a line resistant to 4-hydroperoxycyclophosphamide (4-HC), displays enhanced repair of DNA interstrand crosslinks induced by phosphoramide mustard. D283 Med (4-HCR) cells are cross-resistant to ...
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Journal articleBioconjug Chem · 1999
Radioimmunopretargeting is based on the separate injection of a modified mAb and the radionuclide and most frequently exploits the very high avidity of biotin for streptavidin (SA). Currently, we are evaluating the therapeutic potential of directly labeled ...
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Journal articleCancer Chemother Pharmacol · 1999
PURPOSE: We have previously reported preferential repair of DNA interstrand crosslinks in the 4-hydroperoxycyclophosphamide-resistant human medulloblastoma cell line D-283 Med (4-HCR). We now report further studies that explored the potential mechanisms un ...
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Journal articleJ Neurooncol · 1999
The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated thr ...
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Journal articleClinical Cancer Research · 1999
A single-chain antibody fragment, MR1(scFv), with specific binding to epidermal growth factor receptor-vIII (EGFRvIII), was produced, radiolabeled, and evaluated for biodistribution in human glioma-bearing athymic mice. The mutant receptor EGFRvIII has a d ...
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Journal articleJ Clin Oncol · December 1998
PURPOSE: We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA ...
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Journal articleJ Clin Oncol · November 1998
PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy is the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which removes chlorethylation or methylation damage from the O6-position of guanine. O6-benzylguanine (O6-BG) is an ...
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Journal articleClin Cancer Res · October 1998
The in vivo properties of radiolabeled chimeric monoclonal antibodies (mAbs) with human IgG1 and IgG3 constant regions generally are similar to those of their corresponding murine construct. In contrast, we have observed that chimeric anti-tenascin mAb 81C ...
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Journal articleJ Neuroimmunol · June 1, 1998
We have previously reported that local secretion of either TNF-alpha or TGF beta1 by intracerebral SMA-560 malignant glioma tumor cells can reduce or eliminate tumor growth in mice. However, the use of TNF-alpha, while improving the overall survival of tum ...
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Journal articleJ Clin Oncol · June 1998
PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS ...
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Journal articleClin Cancer Res · June 1998
During replication, the primary function of the eukaryotic DNA mismatch repair (MMR) system is to recognize and correct mismatched base pairs within the DNA helix. Deficiencies in MMR have been reported previously in cases of hereditary nonpolyposis colore ...
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Journal articleJ Neurovirol · April 1998
Any immunotherapeutic approach to cancer cell eradication is based upon the specific recognition of neoplastic cells and the sparing of surrounding normal tissue; perhaps nowhere is this distinction more important than within the central nervous system, du ...
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Journal articleCancer Res · January 15, 1998
It has been hypothesized that transforming growth factor beta (TGF-beta) may prevent immune-mediated glioma cell elimination; however, previous work has also indicated that increased TGF-beta may lead to reduced proliferation, induction of apoptosis, and e ...
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Journal articleCancer Chemother Pharmacol · 1998
PURPOSE: The activity of vinorellbine, a new semisynthetic vinca alkaloid, was evaluated against a battery of human tumor xenografts derived from adult and pediatric CNS malignancies. METHODS: Tumors included adult high-grade gliomas (D-54 MG, D-245 MG), c ...
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Journal articleCancer Chemother Pharmacol · 1998
Two major obstacles in the treatment of patients with central nervous system malignancies are drug resistance and host toxicity. The goal of combination chemotherapy is to achieve therapeutic effects that are more favorable than using a single drug alone, ...
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Journal articleCurr Opin Neurol · December 1997
The failure of conventional therapies for many malignant brain tumors has led to a search for more promising alternatives. Recent advances have elucidated a variety of biological factors that act to determine the growth and invasiveness of central nervous ...
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Journal articleNeurosurgery · December 1997
OBJECTIVE: The promise of immunotherapies developed against brain tumors in animal models has not been realized in human clinical trials. This may be because of the routine use of rodent tumors artificially induced by chemicals or viruses that do not accur ...
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Journal articleJ Exp Med · October 6, 1997
Recent studies have shown that the brain is not a barrier to successful active immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the cen ...
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Journal articleNucl Med Biol · October 1997
The mutant version of the epidermal growth factor receptor EGFRvIII has been found on gliomas and other tumors, but not on normal tissues. Radioiodinated murine (mu) L8A4 monoclonal antibody (MAb) specifically targets EGFRvIII xenografts in vivo when label ...
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Journal articleCancer Res · October 1, 1997
The PTEN gene, located on 10q23, has recently been implicated as a candidate tumor suppressor gene in brain, breast and prostate tumors. In the present study, 123 brain tumors, including various grades and histological types of gliomas occurring in childre ...
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Journal articleCancer Res · September 15, 1997
The potential of therapeutic targeting of tumor cell surface epidermal growth factor receptors (EGFRs) by modified ligands or specific antibodies has been limited by the normal tissue distribution of the receptor. The identification and characterization of ...
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Journal articleJ Neuroimmunol · September 1997
An active immunotherapeutic strategy using transfected allogeneic cells for targeting the mutant epidermal growth factor receptor (EGFRvIII) on intracranial tumors was examined. Immunization with allogeneic 300.19/EGFRvIII cells induced CD8+ cytotoxic T-ly ...
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Journal articleCancer Res · July 15, 1997
A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-me ...
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Journal articleBiochem J · June 15, 1997
The type-III deletion variant of the epidermal growth factor receptor (EGFRvIII) is frequently found in glioblastomas and other malignant human tumours. Although EGFRvIII confers ligand-independent oncogenic transformation of cell lines, the mechanism by w ...
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Journal articleCancer Res · April 15, 1997
Monoclonal antibody (mAb) L8A4, specific for the tumor-associated mutant epidermal growth factor receptor variant III (EGFRvII), is internalized and degraded after cell binding. Four paired-label experiments were performed in athymic mice bearing EGFRvIII- ...
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Journal articleNucl Med Biol · April 1997
A paired-label study was performed in athymic mice bearing subcutaneous D-54 MG human glioma xenografts to compare the localization of human/mouse anti-tenascin chimeric antibody 81C6 labeled by reaction with N-succinimidyl 3-[211At]astatobenzoate and N-su ...
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Journal articleCancer Chemother Pharmacol · 1997
Therapy of patients with malignant central nervous system tumors is frequently unsuccessful, reflecting limitations of current surgical, radiotherapeutic, and pharmacotherapeutic treatments. The camptothecin derivative irinotecan (CPT-11) has been shown to ...
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Journal articleCancer Chemother Pharmacol · 1997
These studies evaluated the efficacy of sequential pretreatment with L-amino acid oxidase (LOX) and LOX antiserum in the modulation of melphalan activity against intracranial glioma in athymic nude mice. LOX produced statistically significant (P < 0.01) de ...
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Journal articleClin Cancer Res · January 1997
This study was undertaken to determine the effect of local hyperthermia on the tissue distribution of a chimeric human/mouse IgG2 monoclonal antibody, 81C6, reactive with the extracellular matrix protein tenascin, which is expressed at high levels in gliom ...
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Journal articleCancer Chemother Pharmacol · 1997
Busulfan is an alkylating agent commonly used in the treatment of chronic myelogenous leukemia and in combination with cyclophosphamide in preparation for allogeneic bone marrow transplantation. Serial treatment of a childhood high-grade glioma xenograft ( ...
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Journal articleCancer Chemother Pharmacol · 1997
The prognosis for patients with malignant gliomas continues to be dismal. The high degree of resistance of gliomas to nitrosourea-based chemotherapy is one major factor in poor treatment outcome. The identification of O6-alkylguanine-DNA alkyltransferase ( ...
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Journal articleProc Natl Acad Sci U S A · December 10, 1996
EGFRvIII is a mutant epidermal growth factor receptor found in glioblastoma, and in carcinoma of the breast, ovary, and lung. The mutant receptor has a deletion in its extracellular domain that results in the formation of a new, tumor-specific extracellula ...
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Journal articleCancer Res · November 1, 1996
Monoclonal antibodies (mAbs) that internalize following binding to cell-surface receptors require radiolabeling approaches that minimize loss of radioactivity from the cell after intracellular processing. One class of internalizing mAbs of great interest f ...
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Journal articleProc Natl Acad Sci U S A · September 17, 1996
Vaccination with cytokine-producing tumor cells generates potent immune responses against tumors outside the central nervous system (CNS). The CNS, however, is a barrier to allograft and xenograft rejection, and established tumors within the CNS have faile ...
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Journal articleMed Pediatr Oncol · July 1996
Leptomeningeal dissemination of childhood pilocytic astrocytoma (PA) is a rare event with little information available regarding therapy. We report here four children with disseminated PA whom we treated with high doses of cyclophosphamide with clinical be ...
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Journal articleGlycoconj J · June 1996
The human glioma D-54MG cell line grown in vitro primarily expresses ganglio series gangliosides, particularly GM2. Subcutaneous injection of these cells into nude mice produced xenografts with an increased content of the human glioma-associated lacto seri ...
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Journal articleClin Cancer Res · June 1996
We aimed to determine the maximum tolerated dose (MTD) of 131I-labeled 81C6 in patients with leptomeningeal neoplasms or brain tumor resection cavities with subarachnoid communication and to identify any objective responses. 81C6 is a murine IgG monoclonal ...
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Journal articleMed Pediatr Oncol · June 1996
The outcome for patients with pineoblastoma has historically been very poor, with most patients dying of disseminated disease despite irradiation. Furthermore, the low incidence of this tumor has hindered progress toward defining better treatment strategie ...
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Journal articleNucl Med Biol · May 1996
When labeled using the Iodogen method, a chimeric antibody composed of the human IgG2 constant region and the variable regions of murine anti-tenascin 81C6 exhibited superior uptake in human glioma xenografts compared with its murine parent. In the current ...
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Journal articleJ Neuropathol Exp Neurol · May 1996
Childhood ependymomas exhibit epidemiologic, anatomic, histologic, and biologic features and distinguish them from other gliomas. Because of their propensity to grow in functionally sensitive regions of the brain, adequate tumor sampling for basic and ther ...
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Journal articleInt J Radiat Oncol Biol Phys · April 1, 1996
PURPOSE: The present study undertook to establish the dose (LD) of systematically administered (via tail vein) sodium [211At]astatide that would kill 10% (LD10) of exposed animals in two mouse models and to evaluate the resulting histologic lesions. METHOD ...
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Journal articleCancer Chemother Pharmacol · 1996
Cyclophosphamide is one of the most active agents in the treatment of medulloblastoma. However, development of resistance to this alkylator frequently occurs and is the harbinger of tumor progression and death. In order to understand the biochemical basis ...
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Journal articleCancer Chemother Pharmacol · 1996
Our previous studies exploring melphalan resistance in the human rhabdomyosarcoma xenograft TE-671 MR revealed elevation of DNA polymerase-alpha and DNA polymerase-beta. The present study evaluated the alteration of melphalan activity in TE-671 (melphalan- ...
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Journal articleNeuroepidemiology · 1996
There has been controversy in the last decade over whether the reported increase in brain tumors reflects a real increase in incidence rates. Incidence data on the full spectrum of brain tumors is lacking in the discussion since current cancer reports in t ...
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Journal articleActa Oncol · 1996
Radionuclides which decay by the emission of alpha-particles are attractive for certain radioimmunotherapeutic applications. These include the treatment of lymphomas, compartmentally spread malignancies such as ovarian cancer and neoplastic meningitis, and ...
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Journal articleProc Natl Acad Sci U S A · December 19, 1995
Phosphoramide mustard-induced DNA interstrand cross-links were studied both in vitro and by computer simulation. The local determinants for the formation of phosphoramide mustard-induced DNA interstrand cross-links were defined by using different pairs of ...
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Journal articleClin Cancer Res · December 1995
LMB-1 (B3-LysPE38) is an immunotoxin composed of the tumor-reactive monoclonal antibody B3 and a genetically engineered form of Pseudomonas exotoxin. Monoclonal antibody B3 reacts with a carbohydrate epitope that is found on a number of solid tumors (e.g., ...
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Journal articleGlia · November 1995
Gliomas affect 15,000 to 17,000 Americans every year and carry a dismal prognosis. The potential of immunologically mediated diagnosis and therapy, although greatly enhanced since the advent of monoclonal antibodies, has not been fully realized due to sign ...
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Journal articleCancer Res · October 1, 1995
Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene are characteristics of many types of tumors. One class of EGFR mutations, EGFRvIII, is characterized by an in-frame deletion resulting in a truncated external domain of the ...
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Journal articleCell Growth Differ · October 1995
The type III deletion-mutant gene for the epidermal growth factor receptor (EGFRvIII) is frequently expressed in glioblastomas and in breast and non-small cell lung carcinomas. To understand its contribution to the malignant phenotype in humans, we transfe ...
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Journal articleCancer Res · September 1, 1995
Malignant gliomas will affect 15,000-17,000 Americans each year and carry a dismal prognosis. Adjuvant chemotherapy is hampered by inadequate drug delivery, systemic toxicity, and a markedly variable biological sensitivity. Intraarterial (i.a.) therapy may ...
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Journal articleMed Pediatr Oncol · September 1995
Thirteen patients with recurrent medulloblastoma were treated with cyclophosphamide in association with Sargramostim. Cyclophosphamide was given at doses ranging between 1.0-2.5 g/m2 daily for two doses. Sargramostim was given at a fixed dose of 250 microg ...
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Journal articleClin Cancer Res · August 1995
Human cancers arise from a series of mutations, many of which direct the expression of mutant proteins with altered functions. These aberrant proteins are attractive targets for new therapeutic agents. One such protein is a mutant epidermal growth factor r ...
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Journal articleCancer Res · July 15, 1995
Despite molecular biological advances in understanding human cancers, translation into therapy has been less forthcoming; targeting neoplastic cells still requires that tumor-specific markers, preferably those on the cell surface, be identified. The epider ...
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Journal articleCancer Res · July 1, 1995
The activity of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin- 4(3H)-one (temozolomide) in the treatment of a panel of xenografts derived from ependymoma, medulloblastoma, and childhood and adult high-grade glioma was evaluated in athymic nude mice b ...
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Journal articleBr J Cancer · June 1995
Flunarizine, a diphenylpiperazine calcium channel blocker, is known to increase tumor blood flow. It also interferes with calmodulin function, repair of DNA damage and drug resistance associated with P-glycoprotein. Flunarizine was tested for its ability t ...
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Journal articleNeurosurgery · May 1995
A new model for human brain tumor uses the intracranial placement of tumor xenografts under transparent glass cranial windows in nude rats, which require no immunosuppression for tumor engraftment. Adult male nude rats underwent implantation of human anapl ...
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Journal articleMed Pediatr Oncol · April 1995
We conducted a dose escalation trial of cyclophosphamide plus Sargramostim in the therapy of patients with newly diagnosed or recurrent central nervous system tumors. Cyclophosphamide was administered at doses ranging between 1.0 and 2.5 g/m2 daily for two ...
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Journal articleProc Natl Acad Sci U S A · March 28, 1995
LMB-7 [B3(Fv)-PE38] is a single-chain immunotoxin constructed from the murine monoclonal antibody B3 and a truncated from of Pseudomonas exotoxin PE38. Antibody B3 recognizes a carbohydrate epitope found on solid tumors that frequently invade the intrathec ...
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Journal articleCancer Chemother Pharmacol · 1995
We have previously shown that diet restriction-induced depletion of large neutral amino acids (LNAAs) in murine plasma to 46% of control significantly enhances intracranial delivery of melphalan without enhancing delivery to other organs. Studies have now ...
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Journal articleJ Neurooncol · 1995
Medulloblastoma, the most common malignancy of childhood, was originally shown to be sensitive to cyclophosphamide in 1981. We have used combined laboratory and clinical investigations to demonstrate the synergy of cyclophosphamide and vincristine in the t ...
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Journal articleInt J Hyperthermia · 1995
These experiments investigate the biodistribution of radiolabelled MAb in a human glioma xenograft model after 4 h of local hyperthermia (HT) with a twofold purpose: to maximize the ratio of cumulative isotope activity in tumour relative to normal tissues, ...
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Journal articleJ Neurooncol · 1995
DNA derived from medulloblastoma biopsies was analyzed to determine if deletions of the 17p region, mutations of the TP53 gene, or amplification of the c-myc, N-myc, EGFR (epidermal growth factor receptor), or MDM2 (murine double-minute-2) genes was indica ...
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Journal articleJ Neurooncol · 1995
The advent of monoclonal antibody (MAb) technology has made Ehrlich's postulate of the 'magic bullet' an attainable goal. Although specific localization of polyvalent antibodies to human gliomas was demonstrated in the 1960s, the lack of specific, high aff ...
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Journal articleCancer Res · December 15, 1994
We have used molecular genetic methods to examine the status of cell cycle-inhibitory genes in human brain tumors. We found that p16 and a neighboring gene, p15, were often homozygously deleted in glioblastoma multiformes but not in medulloblastomas or epe ...
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Journal articleCancer Res · September 1, 1994
We report the activity and toxicity of intrathecal melphalan in the treatment of human neoplastic meningitis in the subarachnoid space of athymic nude rats. Animals received injections via chronic indwelling subarachnoid catheters with 5 x 10(5) or 5 x 10( ...
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Journal articleCancer Res · September 1, 1994
Because of their short range and high linear energy transfer, alpha-particles may be particularly effective in the treatment of neoplastic meningitis. Monoclonal antibody 81C6 was labeled with alpha-particle-emitting 211At using N-succinimidyl3-[211At]asta ...
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Journal articleCancer Res · July 1, 1994
Previous investigations have revealed that the human TE-671 MR human rhabdomyosarcoma xenograft selected in vivo for melphalan resistance (M. C. Rosenberg, et al., Cancer Res., 49: 6917-6922, 1989) is cross-resistant to a wide variety of alkylating agents ...
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Journal articleJ Neuroimmunol · July 1994
The murine anti-tenascin monoclonal antibody 81C6, following iodination, has been shown to be an efficient localizing and therapeutic agent in both subcutaneous and intracranial human glioma xenograft models in athymic mice and rats. Similarly, effective m ...
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Journal articleBrain Pathol · July 1994
The immunohistochemical localization of glial fibrillary acidic protein has proven its utility in the histologic identification of benign astrocytes and neoplastic cells of glial lineage in the central nervous system. Its application in the developing nerv ...
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Journal articleHybridoma · April 1994
Murine monoclonal antibody Me1-14, which recognizes an epitope on chondroitin proteoglycan sulfate expressed in malignant glioma and melanoma, has been used for radioimmunolocalization and therapy both in animal models and in patients. Here, we report the ...
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Journal articleCancer Res · March 1, 1994
Glial tumors of all grades and histological types from 72 adults and 48 children were analyzed for mutations of the TP53 gene, loss of heterozygosity (LOH) for 17p, and accumulation of TP53 protein to determine whether the incidence and type of TP53 altera ...
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Journal articleCancer Chemother Pharmacol · 1994
We evaluated the antitumor activity of busulfan against a panel of tumor cell lines and xenografts in athymic nude mice derived from childhood high-grade glioma, adult high-grade glioma, ependymoma, and medulloblastoma. Busulfan displayed similar activity ...
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Journal articleMol Chem Neuropathol · 1994
A library of epitope-defined antiganglioside monoclonal antibodies has been used to analyze the ganglioside phenotype of human glioma cell lines, rodent xenografts derived from them, and a separate panel of human glioma biopsies by multiple quantitative an ...
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Journal articleCancer Chemother Pharmacol · 1994
The activity of dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts derived from ependymomas (D528 EP, D612 EP), childhood high-grade gliomas (D-456 MG, D-212 MG), adult high-grade gliomas (D-245 MG, D-54 MG), ...
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Journal articleProg Brain Res · 1994
In this study, MAbs to the 'conventional' gangliosides expressed by human gliomas were generated and used to detect ganglioside species previously unisolated or defined in normal adult CNS tissue. Despite the marked phenotypic and genotypic heterogeneity s ...
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Journal articleNucl Med Biol · October 1993
The potential utility of N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC) for the radioiodination of monoclonal antibodies was investigated. Paired-label studies were performed using the anti-tenascin antibody 81C6 in athymic mice bearing subcutaneous D- ...
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Journal articleHum Pathol · September 1993
The expression of tenascin, an extracellular matrix glycoprotein, was studied in three human prostatic carcinoma cell lines by Northern and Western blot analyses and in human prostate tissues by immunohistochemistry and Western blot analysis. All three car ...
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Journal articleCancer Res · July 15, 1993
The development of novel immunotherapy strategies for non-small cell lung cancer (NSCLC) will be facilitated by the identification of tumor-specific targets. Although the epidermal growth factor receptor (EGFR) is overexpressed in many cases of NSCLC, its ...
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Journal articleJ Neuroimmunol · July 1993
We have previously demonstrated antibody production to a glioma-associated variant form of the human epidermal growth factor receptor in rabbits that had received a synthetic peptide mimicking the unique primary structure of the variant protein as immunoge ...
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Journal articleInvest Radiol · June 1993
RATIONALE AND OBJECTIVES: Monoclonal antibody 81C6 reacts with the extracellular matrix antigen, tenascin, present on gliomas and other tumors, as well as several normal tissues, including spleen and liver tissue. Single photon emission computed tomography ...
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Journal articleCancer Res · May 15, 1993
The addition of chemotherapy, notably using nitrosoureas, in the treatment of patients with glioblastoma multiforme has resulted in only modest improvements in long-term patient survival over the use of surgical intervention and irradiation alone. Intraart ...
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Journal articleCancer Chemother Pharmacol · 1993
The tolerated dose of melphalan is limited by bone marrow suppression; when this complication is ameliorated by bone marrow transplantation, the dose-limiting toxicity becomes gastrointestinal mucositis. No intervention to date has been successful in modul ...
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Journal articleOncol Res · 1993
Cellular levels of O6-methylguanine-DNA methyltransferase (MGMT) correlate strongly with cellular resistance to carcinogenic and chemotherapeutic agents that produce adducts at the O6-position of guanine in DNA. Although biochemical and molecular assays ca ...
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Journal articleCancer Res · January 1, 1993
Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuA ...
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Journal articleJ Clin Oncol · January 1993
PURPOSE: We conducted a phase III trial comparing intravenous (IV) diaziquone (AZQ) and carmustine (BCNU) as single agents in patients with cerebral anaplastic gliomas who had received surgery and radiotherapy. Its purpose was to compare the efficacy of AZ ...
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Journal articleCancer Research · January 1, 1993
The addition of chemotherapy, notably using nitrosoureas, in the treatment of patients with glioblastoma multiforme has resulted in only modest improvements in long-term patient survival over the use of surgical intervention and irradiation alone. Intraart ...
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Journal articleJ Natl Cancer Inst · December 16, 1992
BACKGROUND: Although chemotherapy offers promise of increased survival for children with medulloblastoma and glioblastoma multiforme, drug resistance occurs frequently, resulting in tumor progression and death. Resistance to nitrosoureas and methylating ag ...
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Journal articleCancer Res · October 15, 1992
Melphalan (L-phenylalanine mustard, L-PAM, alkeran; molecular weight, 305,000) is transported across tumor cell membranes and the blood-brain barrier by the large neutral amino acid (LNAA) transport system. Normally, plasma LNAA levels are high enough and ...
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Journal articleMol Chem Neuropathol · October 1992
Operationally specific monoclonal antibodies (MAbs) reactive with tumor but not normal adult tissues offer great potential for diagnosis and therapy of CNS neoplasms. Two targets for specific MAb localization were chosen for this study: (1) glioma-associat ...
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Journal articleCancer Res · October 1, 1992
Mechanisms of tumor resistance to 4-hydroperoxycyclophosphamide (4-HC) were studied by using a panel of human medulloblastoma cell lines either passaged in the laboratory for resistance to 4-HC or established from tumors showing clinical resistance to cycl ...
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Journal articleCancer Res · September 15, 1992
Positron emission tomography is an imaging method that might improve the effectiveness of radioimmunoscintigraphy and might provide more accurate estimates of monoclonal antibody dosimetry prior to therapy. Because of its widespread availability, 2-h half- ...
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Journal articleInt J Cancer · August 19, 1992
Ten patients with neoplastic meningitis were treated with a variety of 131I-monoclonal antibody (MAb) conjugates, chosen to bind to their particular malignancy. Pharmacokinetic studies revealed that MAbs leave the ventricular compartment, enter the sub-ara ...
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Journal articleJ Nucl Med · August 1992
Monoclonal antibody fragments labeled with 18F could be useful for PET if selective tumor uptake could be achieved within a few half-lives of this nuclide. To evaluate this possibility, the F(ab')2 fragment of Mel-14, an antibody reactive with gliomas and ...
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Journal articleGenes Chromosomes Cancer · July 1992
Cytogenetic and RFLP studies have shown that chromosome 10 is frequently lost in tumor cells from glioblastomas, suggesting that a suppressor gene important in tumorigenesis is present on this chromosome. Forty-one tumors were examined for loss of heterozy ...
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Journal articleCurr Opin Oncol · June 1992
High-grade malignancies of the central nervous system continue to be refractory to multimodality therapy. Immunotherapy with monoclonal antibodies, biologic response modifiers (eg, interleukin-2), and autologous, activated lymphocytes offer the potential f ...
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Journal articleProc Natl Acad Sci U S A · April 1, 1992
The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas, and the amplified genes are frequently rearranged. We have characterized the genetic alterations associated with these rearrangements in five malignant gliomas. In o ...
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Journal articleBiochim Biophys Acta · March 16, 1992
To examine the role of the ligand binding domain of epidermal growth factor receptor in its dimerization, we studied the dimerization of a truncated form of the receptor that resembles v-erbB in that it lacks a ligand binding domain. Receptor dimerization ...
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Journal articleCancer Res · March 1, 1992
Six well characterized human medulloblastoma cell lines (D283 Med, Daoy, D341 Med, D384 Med, D425 Med, and D458 Med) were examined for the expression of O6-methylguanine-DNA methyltransferase (MGMT) by activity and Western and Northern blot analysis. High ...
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Journal articleBiochemistry · February 25, 1992
A mouse cDNA clone encoding O6-methylguanine-DNA methyltransferase (MGMT), responsible for repair of mutagenic O6-alkylguanine in DNA, was cloned from a lambda gt11 library. On the basis of an open reading frame in cDNA, the mouse protein contains 211 amin ...
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Journal articleRadiat Res · February 1992
The effects of regional hyperthermia (42 degrees C for 70 min) on the antitumor activity of melphalan were examined in athymic mice bearing melphalan-resistant human rhabdomyosarcoma (TE-671 MR) xenografts growing in the right hind limb, and results were c ...
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Journal articleInt J Radiat Oncol Biol Phys · 1992
We have used an extensively characterized human glioma cell line in an athymic mouse model to evaluate new therapeutic approaches for human supratentorial high grade gliomas. The tumor, D-54MG, is a subline of a human anaplastic glioma. Eight days after ho ...
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Journal articleOncol Res · 1992
Human tumor cell lines that do not express O6-methylguanine-DNA methyltransferase (MGMT) in detectable quantities (Mer-) are hypersensitive to the effects of O6-guanine-alkylating agents. Because the Mer- phenotype enhances tumor response to such agents, w ...
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Journal articleActa Cytol · 1992
The cytologic evaluation of poorly differentiated tumors frequently poses a diagnostic dilemma as to the tissue of origin. To assess the diagnostic utility of monoclonal antibodies (MAbs) in these situations, we applied a panel of three highly purified MAb ...
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Journal articleJ Neuroimmunol · January 1992
Tenascin expression was evaluated in 21 human glioma cell lines and in normal adult tissue extracts by Western and Northern blotting. The cell lines differed in their relative expression of tenascin in the cell-associated and supernatant compartments. Glio ...
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Journal articleInt J Hyperthermia · 1992
Investigations with the melphalan-sensitive and -resistant human rhabdomyosarcoma xenografts TE-671 and TE-671 MR were performed to examine the effect of glutathione and polyamine modulation on thermosensitivity. Regimens of intraperitoneally injected and ...
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Journal articleInt J Hyperthermia · 1992
Both hyperthermia and glutathione depletion have been shown to increase the antineoplastic activity of melphalan. Investigations were carried out to define the toxicity and activity of melphalan given in conjunction with local (right hind limb) hyperthermi ...
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Journal articleInternational Journal of Radiation Oncology, Biology, Physics · 1992
We have used an extensively characterized human glioma cell line in an athymic mouse model to evaluate new therapeutic approaches for human supratentorial high grade gliomas. The tumor, D-54MG, is a subline of a human anaplastic glioma. Eight days after ho ...
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Journal articleJ Neuropathol Exp Neurol · November 1991
Monoclonal antibodies (MAb; DMAb, monoclonal antibodies derived at Duke Medical Center) directed against the oncofetally expressed lactotetraosyl gangliosides 3'-isoLM1 (IV3NeuAc-LcOse4Cer) and 3',6'-isoLD1 (IV3NeuAc,III6NeuAc-LcOse4Cer) were produced and ...
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Journal articleMutat Res · September 1991
Transfection of Chinese hamster ovary (CHO) cells with human DNA has been shown in several laboratories to produce clones which stably express the DNA-repair protein, O6-methylguanine-DNA methyltransferase (MGMT), that is lacking in the parent cell lines ( ...
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Journal articleCarcinogenesis · September 1991
When animals are treated with carcinogenic agents that alkylate O6-guanine residues, the incidence of tumors in specific tissues often relates inversely to the level of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) present in the tiss ...
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Journal articleCancer Res · September 1, 1991
Cytogenetic and molecular studies of medulloblastomas have demonstrated frequent loss of sequences from the short arm of chromosome 17, possibly implicating loss or inactivation of the p53 tumor suppressor gene. We amplified exons 5 through 8 of the p53 ge ...
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Journal articleCancer Res · September 1, 1991
The effects of four anti-GM2 monoclonal antibodies (DMAb-1, DMAb-2, DMAb-3, and DMAb-5) were studied on spheroid cultures from a human glioma cell line (D-54 MG) that is known to express high levels of GM2. The spheroids developed central necrosis 48 h aft ...
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Journal articleBiochem Biophys Res Commun · August 15, 1991
Malignant human glioma D-298 MG amplifies a rearranged epidermal growth factor receptor (EGFR) gene (c-erbB proto-oncogene), resulting in an in-frame deletion of 83 amino acids in domain IV of the extracellular domain of the EGFR. EGF and transforming grow ...
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Journal articleCancer Res · August 15, 1991
Improvements in efficacy of radioimmunotherapy will require increased tumor uptake relative to normal tissue. We previously demonstrated that labeling the IgG2b glioma-reactive antitenascin monoclonal antibody 81C6 with 131I using N-succinimidyl-3-(tri-n-b ...
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Journal articleJ Neurooncol · August 1991
Medulloblastoma is the most common central nervous system malignancy of childhood, with approximately 350 new cases seen in the United States each year. Although the low incidence of this tumor, compared with adult neoplasms such as breast or colon carcino ...
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Journal articleCancer Res · August 1, 1991
Investigations with the melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR were carried out to identify patterns of cross-resistance and collateral sensitivity and to define the mechanism(s) mediating melphalan resistance. TE-671 MR was cross-r ...
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Journal articleCancer Res · July 1, 1991
Four synthetic peptides from the sequence of human O6-methylguanine-DNA methyltransferase (MGMT), three corresponding to different hydrophilic regions and one corresponding to the sequence containing the alkyl acceptor residue cysteine 145, were used to im ...
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Journal articleLab Invest · June 1991
Three new human medulloblastoma (MB) cell lines (D384 Med, D425 Med, and D458 Med) and their transplantable xenografts were examined for antigenic expression with antibodies against neuroectodermal antigens, cytoskeletal proteins, neuroendocrine markers, g ...
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Journal articleNeurol Clin · May 1991
Virtually all brain tumor models studied to date have demonstrated the activity of the nitrosoureas, an observation confirmed in a cohort of adult patients with high-grade gliomas. However, studies with animal brain tumor models have not led to the selecti ...
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Journal articleBiochim Biophys Acta · February 5, 1991
Medulloblastoma biopsies are heterogenous and might contain normal brain tissue, which limits the usefulness of such tumor material for biochemical analyses. We have, therefore, examined the gangliosides and their metabolism using the medulloblastoma cell ...
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Journal articleJ Biol Chem · January 15, 1991
O6-Methylguanine-DNA methyltransferase, a ubiquitous and unusual DNA repair protein, eliminates mutagenic and cytotoxic O6-alkylguanine from DNA by transferring the alkyl group to one of its cysteine residues in a second-order suicide reaction. This 22-kDa ...
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Journal articleCancer Chemother Pharmacol · 1991
Melphalan-induced toxicity in nude mice following pretreatment with a regimen of L-buthionine sulfoximine (BSO), previously shown to enhance the activity of this alkylating agent against rhabdomyosarcoma and glioma xenografts, was examined. Mice were pretr ...
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Journal articleCancer Chemother Pharmacol · 1991
We used human anaplastic glioma xenografts to evaluate the therapeutic efficacy of combinations of alkylating drugs, either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-(2,5-dioxo-3-piperidyl)-1-nitrosourea (PCNU), or procarbazine, and ...
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Journal articleInvasion Metastasis · 1991
Medulloblastoma, a highly malignant pediatric tumor of the posterior fossa, demonstrates a marked propensity for leptomeningeal dissemination. Although the predominant site of relapse is the posterior fossa, the prevention of subarachnoid spread would be o ...
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Journal articleActa Neuropathol · 1991
Monoclonal antibodies (mAbs) recognizing the disialoganglioside II3(NeuAc)2GgOse3Cer (GD2) were produced by immunizing mice with the GD2-expressing neuroblastoma cell line LAN-1 and a prefusion boost with purified GD2 coupled to Salmonella minnesota. Two I ...
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Journal articleCancer Res · December 15, 1990
Both permanent cultured cell lines and athymic mouse xenografts were established from two human glioblastomas. Biopsies from D-245 MG and D-270 MG contained amplified and rearranged epidermal growth factor receptor (EGFR) genes. Although the gene amplifica ...
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Journal articleJ Neurochem · October 1990
The ganglioside composition of six human medulloblastomas was analyzed. The characterization was performed by thin-layer chromatography, sialidase hydrolysis, and immunological staining with a panel of characterized antiganglioside monoclonal antibodies. T ...
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Journal articleCancer Res · September 15, 1990
Effects of epidermal growth factor (EGF) and an antibody (Ab-528) reactive against the binding site for EGF on human EGF receptors were studied on multicellular tumor spheroids obtained from three human glioma cell lines with high (D-37 MG), medium (D-247 ...
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Journal articleActa Neurol Scand · September 1990
This study investigated whether tumor-associated gangliosides or glycoproteins may be markers for meningiomas in CSF. The concentrations of a number of gangliosides and sulphatide were determined with specific monoclonal antibodies and cholera toxin B-subu ...
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Journal articleBiochim Biophys Acta · August 6, 1990
This study was undertaken to characterize gangliosides in the human glioma cell line U-118 MG. The cell line was grown both in cell culture and as xenografts in nude rats. A common finding in both culture and xenograft cells was the high proportion of the ...
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Journal articleCancer Genet Cytogenet · July 15, 1990
The most frequent cytogenetic alterations in primary brain tumors are losses of chromosomes or chromosomal regions and the presence of double minute chromosomes (dmins). The regions which are lost and the genes which are amplified are distinctive for indiv ...
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Journal articleCancer Res · July 1, 1990
Non-i.v. delivery of radiolabeled monoclonal antibodies (MAbs) has been shown to increase tumor uptake and decrease dose to normal tissues. In this study, we have examined the potential advantage of intracarotid (i.c.) versus i.v. administration for the de ...
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Journal articleProc Natl Acad Sci U S A · June 1990
We have investigated human gliomas that amplify and rearrange the epidermal growth factor receptor gene, with generation of an in-frame deletion mutation of 802 nucleotides in the external domain. This in-frame deletion mutation generates a local amino aci ...
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Journal articleCancer Res · May 15, 1990
Despite a considerable amount of information concerning chromosomal and molecular abnormalities found in gliomas in adults, relatively little is known regarding these abnormalities in pediatric brain tumors. We have analyzed DNA from 37 primary brain tumor ...
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Journal articleJ Neurosurg · May 1990
The development of the Cavitron ultrasonic surgical aspirator (CUSA) has facilitated neurosurgical intervention for removal of central or peripheral nervous system tumors adjacent to or within vital structures. However, laboratory studies defining the phen ...
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Journal articleBiochim Biophys Acta · April 17, 1990
Several derivatives of ganglioside GM2 were synthesized for mapping of the binding epitope of a monoclonal antibody raised against this ganglioside. The GM2 ganglioside was modified in both the hydrophobic and the hydrophobilic part of the molecule. The sy ...
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Journal articleCancer Res · April 15, 1990
Administration of cyclophosphamide at a dose which is lethal to 10% of control athymic nude mice resulted in sudden death within 3 h in all mice that had been pretreated with the glutathione synthesis inhibitor L-buthionine-SR-sulfoximine. In Fischer 344 r ...
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Journal articleCancer Res · April 15, 1990
Cultured cell lines and xenografts derived from 7 human medulloblastomas were evaluated for amplification of the c-myc, N-myc, epidermal growth factor receptor, and gli genes by Southern blot analysis. Karyotypes of the original biopsies and early passaged ...
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Journal articleCancer Res · March 15, 1990
The purpose of this study was to investigate the effects of tumor-localized hyperthermia at 42 degrees C on the tissue distribution of radioiodinated monoclonal antibody F(ab')2 fragments. Paired-label biodistribution measurements were performed in athymic ...
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Journal articleCancer Res · March 15, 1990
The administration of radiolabeled monoclonal antibodies to improve the treatment of malignant gliomas is dependent upon achieving effective tumor radiation dose while sparing normal tissues. We have evaluated the efficacy of 131I-labeled F(ab')2 fragment ...
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Journal articleCancer Res · March 15, 1990
Neoplastic meningitis can result from leptomeningeal dissemination of a variety of cancers. We now report the development of animal models of human neoplastic meningitis and activity of intrathecal 4-hydroperoxycyclophosphamide (4-HC) against the human rha ...
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Journal articleCancer Res · February 15, 1990
Buthionine sulfoximine (BSO) is an inhibitor of glutathione synthesis and can be used to potentiate the effects of chemotherapeutic alkylating agents and radiotherapy. We examined the rates of influx and efflux of [35S]BSO administered to athymic mice with ...
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Journal articleNeurosurgery · February 1, 1990
AbstractAn intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-bu ...
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Journal articleNeurosurgery · February 1990
An intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-buthionine-S,R-sulfoximine (L-BSO)-mediated depletion of tu ...
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Journal articleNeuropathol Appl Neurobiol · February 1990
A transplantable subcutaneous tumour (designated D-212 MG), sequentially passaged in athymic nude mice and originally derived from a human giant cell glioblastoma, was maintained in an organ culture (matrix) system and studied immunohistochemically after i ...
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Journal articleCancer Res · January 15, 1990
Based on previous work demonstrating the activity of cyclophosphamide and melphalan in a series of human medulloblastoma and rhabdomyosarcoma cell lines and transplantable xenografts, investigations were conducted to define the effects of combining cycloph ...
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Journal articleActa Cytol · 1990
Five antibodies, 2D.1 (pan-leukocyte), AE-1,3 (anti-keratin), B72.3 (anti-carcinoma), ME 1-14 (alpha-chondroitin sulfate proteoglycan) and polyclonal S-100 protein (P-S100), were tested to determine if this panel could be used immunocytochemically to diffe ...
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Journal articleCancer Res · January 1, 1990
As well as repairing mutagenic lesions induced by simple methylating agents, O6-alkylguanine-DNA alkyltransferase repairs precursors of cytotoxic interstrand cross-links induced by chloroethylating anticancer drugs. Moreover, levels of the transferase corr ...
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Journal articleCancer Res · December 15, 1989
A melphalan-resistant human rhabdomyosarcoma xenograft, TE-671 MR, was established in athymic mice by serial melphalan treatment of the parent xenograft, TE-671, at the 10% lethal dosage (LD10); significant resistance was evident after ten passages of the ...
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Journal articleCancer Research · December 15, 1989
A melphalan-resistant human rhabdomyosarcoma xenograft, TE-671 MR, was established in athymic mice by serial melphalan treatment of the parent xenograft, TE-671, at the 10% lethal dosage (LD10); significant resistance was evident after ten passages of the ...
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Journal articleJ Neurosurg · December 1989
In a controlled study of interstitial radiotherapy in the avian sarcoma virus (ASV)-induced glioma model in rats, prolongation of survival was demonstrated (p = 0.08 in Experiment 1 and p = 0.03 in Experiment 2) following mean dosages of 7582 to 9902 cGy 1 ...
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Journal articleCancer Res · December 1, 1989
In order to investigate GM2 expression in gliomas, the GM2-positive human glioma cell line (HGL) D-54 MG, which contains 0.6 nmol GM2/mg protein, representing 77% of the total monosialoganglioside fraction, was used as an immunogen for the production of an ...
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Journal articleCancer Res · October 15, 1989
Loss of radiolabel after in vivo administration of labeled monoclonal antibodies (MAbs) to cancer patients is a likely cause of the low levels of tumor uptake of MAb which have been observed. In this study, we have evaluated the utility of N-succinimidyl 3 ...
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Journal articleLab Invest · September 1989
The immunocytochemical demonstration of intermediate filament proteins in three human neuroepithelial tumor cell lines maintained in vitro on a three-dimensional matrix was correlated with the proportion of cells in S phase. The cell lines of a medulloblas ...
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Journal articleProc Natl Acad Sci U S A · September 1989
alpha-Particles such as those emitted by 211At may be advantageous for radioimmunotherapy since they are radiation of high linear energy transfer, depositing high energy over a short distance. Here we describe a strategy for labeling monoclonal antibodies ...
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Journal articleJ Biol Chem · July 25, 1989
A monoclonal antibody produced by immunization with cells of the human glioma cell line D-54 MG reacted with ganglioside GM2. The binding epitope of the antibody was found to be GalNAc beta 1-4(NeuAc alpha 2-3)Gal. Immunological detection of glycolipid ant ...
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Journal articleJ Clin Oncol · July 1989
We conducted a phase II study of intravenous (IV) melphalan in the treatment of children with recurrent medulloblastoma and in the initial treatment of children with poor-prognosis medulloblastoma and pineoblastoma. There was one complete response (CR) and ...
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Journal articleCancer Genet Cytogenet · July 1, 1989
The karyotypes of seven human glioblastomas were followed through serial subcutaneous passage in athymic mice. One tumor maintained the same hypodiploid stemline as seen in the original biopsy. Three tumors that originally had near-diploid stemlines showed ...
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Journal articleJ Cell Biol · June 1989
Tenascin/hexabrachion is a large glycoprotein of the extracellular matrix. Previous reports have demonstrated that tenascin is associated with epithelial-mesenchymal interfaces during embryogenesis and is prominent in the matrix of many tumors. However, th ...
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Journal articleCancer Res · May 15, 1989
We previously have reported that radioiodinated anti-tenascin monoclonal antibody 81C6 exhibits therapeutic potential against both s.c. and intracranial human glioma xenografts in athymic mice and rats. Herein we report the selective tumor localization of ...
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Journal articleJ Natl Cancer Inst · April 5, 1989
In previous studies we demonstrated that administration of buthionine sulfoximine (BSO) to athymic BALB/c mice bearing intracranial human glioma xenografts resulted in highly selective depletion of glutathione in neoplastic tissue with minimal effects on c ...
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Journal articleJ Neurosurg · April 1989
The level of O6-alkylguanine-deoxyribonucleic acid (DNA) alkyltransferase (AT) was determined in 15 human brain-tumor xenografts in athymic mice. This enzyme is a primary intracellular repair mechanism for lesions produced at the O6 position of guanine by ...
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Journal articleJ Neuropathol Exp Neurol · January 1989
An extensive panel of monoclonal antibodies (MAb) and monospecific antisera reactive against neuroectodermal-, neuronal-, glial-, and lymphoid-associated antigens, extracellular matrix, HLA, and cell-surface receptors was used to characterize the phenotype ...
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Journal articleActa Neuropathol · 1989
The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE-671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed ...
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Journal articleCancer Commun · 1989
The response of human cells to the mutagenic, carcinogenic, and lethal effects of alkylating agents that produce O6-alkylguanine adducts in DNA is largely determined by the cellular content of O6-alkylguanine-DNA alkyltransferase. Because a subgroup of hum ...
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Journal articleActa Neuropathol · 1989
Seven monoclonal antibodies (mAbs) reactive with ganglioside II3(NeuAc)2-LacCer (GD3) were generated; four of these mAbs (DMAb-21, DMAb-22, DMAb-23, and DMAb-24) by immunizing mice with GD3 adsorbed to Salmonella minnesota and the remaining three (DMAb-7, ...
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Journal articleInt J Rad Appl Instrum A · 1989
N-succinimidyl-3-(tri-n-butylstannyl)benzoate (m-BuATE), N-succinimidyl-3-(tri-methylstannyl)benzoate (m-MeATE) and N-succinimidyl-4-(tri-n-butylstannyl)benzoate (p-BuATE) were synthesized and radioiodinated using either N-chlorosuccinimide (NCS) or t-buty ...
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Journal articleJournal of Neurosurgery · 1989
The level of O6-alkylguanine-deoxyribonucleic acid (DNA) alkyltransferase (AT) was determined in 15 human brain-tumor xenografts in athymic mice. This enzyme is a primary intracellular repair mechanism for lesions produced at the O6 position of guanine by ...
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Journal articleBiochem Pharmacol · November 15, 1988
D-54 MG, a human glioma-derived continuous cell line growing as subcutaneous or intracranial xenografts in athymic mice, was found to be sensitive to the effects of D,L-buthionine-(SR)-sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase ...
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Journal articleCancer Res · October 15, 1988
Monoclonal antibodies (MAbs) targeted to glioma-associated antigens may allow the selective delivery of imaging and therapeutic agents to brain tumors; the use of MAb fragments may be a strategy to further improve tumor uptake of such agents relative to no ...
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Journal articleCancer Res · October 1, 1988
Melphalan transport, glutathione levels, and glutathione-S-transferase activity were measured in two continuous human medulloblastoma cell lines and transplantable xenografts in athymic nude mice, TE-671 and Daoy. In vitro mean glutathione levels were 10.0 ...
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Journal articleCancer Res · August 1, 1988
A series of bifunctional alkylators were tested against the genotypically and phenotypically heterogeneous continuous human medulloblastoma cell lines, TE-671, Daoy, and D283 Med in vitro and against TE-671 and Daoy growing as s.c. and intracranial xenogra ...
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Journal articleCancer Res · May 15, 1988
Lack of tumor specificity renders current modalities for treating malignant glioma ineffective. The administration of 131I-labeled monoclonal antibody (Mab) 81C6, which reacts with the glioma-associated extracellular matrix antigen, tenascin, to nude mice ...
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Journal articleCancer Res · May 15, 1988
The effect and therapeutic consequences of buthionine-(SR)-sulfoximine (BSO)-mediated depletion of glutathione in the human medulloblastoma-derived cell line, TE-671, growing as s.c. xenografts in athymic nude mice were examined. The glutathione content of ...
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Journal articleJ Neuropathol Exp Neurol · May 1988
Gene amplification occurs in 45-50% of malignant human gliomas (MHG). In the present study, 64 genetically characterized gliomas were evaluated to determine if tumors with amplification of the epidermal growth factor receptor (EGFR), N-myc, c-myc, or gli g ...
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Journal articleCancer Res · April 15, 1988
Xenografts from eight malignant human gliomas were established in athymic mice and were used to study amplification and expression of the epidermal growth factor receptor (EGFR) gene. Tissue identity between biopsy and xenografts was confirmed by karyotypi ...
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Journal articleAm J Pathol · March 1988
D341 Med is a new continuous cell line and transplantable xenograft derived from a cerebellar medulloblastoma. This line grew in vitro in suspension culture with spontaneous macroscopic spheroid formation and demonstrated 20-fold amplification of c-myc. Cu ...
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Journal articleCancer Res · February 1, 1988
The development of Mabs, particularly those reactive with primary brain tumors but not with normal brain, provides a potential means of delivering therapeutic agents selectively to human malignant gliomas. Mab 81C6, an IgG2b immunoglobulin, which defines a ...
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Journal articleCancer Res · January 15, 1988
Karyotypic analysis of 54 malignant human gliomas (5 anaplastic astrocytomas, 43 glioblastoma multiformes, 3 gliosarcomas, 2 giant cell glioblastomas, 1 anaplastic mixed glioma) has demonstrated that 12 tumors contained normal stemlines or only lacked one ...
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Journal articleCancer Research · January 1, 1988
The development of Mabs, particularly those reactive with primary brain tumors but not with normal brain, provides a potential means of delivering therapeutic agents selectively to human malignant gliomas. Mab 81C6 an IgG2b immunoglobulin, which defines an ...
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Journal articleActa Neuropathol · 1988
Epidermal growth factor (EGF) has been shown to stimulate DNA synthesis and cell division in normal glia. At least half of malignant human gliomas (MHG) express high levels of the EGF receptor (EGFR), which are above those detected in normal brain. The dem ...
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Journal articleBr J Neurosurg · 1988
The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In ...
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Journal articleCancer Genet Cytogenet · January 1988
Seven human medulloblastomas (four primary cerebellar, three recurrent or metastatic) were karyotyped in direct preparation and/or short-term or early culture. One tumor had a 46,XX stem line. Four of the six remaining tumors contained one or more i(17q), ...
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Journal articleNeurology · December 1987
Adenosine was infused intravenously at 10 mumol/(kg.min) into athymic ("nude") rats with intracerebral D-54MG xenotransplanted brain tumors, in an attempt to increase tumor blood flow. Cerebral blood flow (F) was measured with 14C-iodoantipyrine and quanti ...
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Journal articleJ Neuropathol Exp Neurol · November 1987
The distribution of type VI collagen was examined immunohistochemically in normal tissues and in 24 human gliomas and six medulloblastomas. Its localization in the neoplasms was compared with that of fibronectin and glioma-mesenchymal extracellular matrix ...
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Journal articleCancer Genet Cytogenet · November 1987
Biopsies of 33 malignant human gliomas were karyotyped and evaluated for amplification (more than eight gene copies per cell) of the epidermal growth factor receptor (EGFR), N-myc, c-myc, and gli genes by Southern blot analysis. Fifteen of 33 tumors showed ...
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Journal articleProc Natl Acad Sci U S A · October 1987
Primary malignant gliomas from 63 patients were analyzed to determine the relationship between amplification of the gene encoding the epidermal growth factor receptor (EGFR) and expression of the corresponding mRNA. Twenty-four tumors were found to have am ...
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Journal articleAnal Quant Cytol Histol · October 1987
DNA content, as determined by flow cytometry (FCM), and ploidy, as determined planimetrically from chromosomes, were measured for 17 established human glioma-derived cell lines. Values obtained by these methods corresponded well for two of two near-diploid ...
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Journal articleCancer Treat Rep · September 1987
We treated D-54 MG, an extensively characterized human glioma tumor line, in athymic mice with each of 20 antineoplastic drugs and two radiation doses. PCNU, melphalan, cyclophosphamide, and fludarabine were highly active against sc tumors. A single radiat ...
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Journal articleCancer Res · August 15, 1987
The pharmacokinetics and regional tissue distribution of two IgG2b immunoglobulins were studied in athymic mice with D54MG human glioma xenografts. Monoclonal antibody (Mab) 81C6, an antiglioma antibody, had a plasma half-life of 2.7 +/- 0.3 (SE) days; 45. ...
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Journal articleJ Natl Cancer Inst · July 1987
Neonatal Fischer 344 rats were immunosuppressed with antithymocyte serum and later were given an injection intracerebrally of cells from the human glioma permanent line D-54MG. Symptomatic tumor-bearing rats were studied with double-label quantitative auto ...
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Journal articleJ Neuroimmunol · May 1987
Radioiodinated murine monoclonal antibodies (Mabs) 81C6, Me 1-14, C12, D12, and E9, made against or reactive with human gliomas but not normal brain, and Mab UJ13A, a pan-neuroectodermal Mab reactive with normal human glial and neural cells, were evaluated ...
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Journal articleScience · April 3, 1987
A gene, termed gli, was identified that is amplified more than 50-fold in a malignant glioma. The gene is expressed at high levels in the original tumor and its derived cell line and is located at chromosome 12 position (q13 to q14.3). The gli gene is a me ...
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Journal articleCancer Res · April 1, 1987
Monoclonal antibody 81C6, which is directed against a human gliomamesenchymal extracellular matrix antigen, was used to evaluate the potential advantage of intracarotid (i.c.) administration versus i.v. delivery to D-54 MG human glioma intracranial xenogra ...
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Journal articleCancer Res · March 15, 1987
We used double-label quantitative autoradiography to study blood flow (with [131I]iodoantipyrine) and blood-to-tissue transport (with [14C]-alpha-aminoisobutyric acid) in 20 TE-671 medulloblastomas xenotransplanted into nude rats. Microscopically, two dist ...
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Journal articleAm J Pathol · February 1987
The majority of cells in a rapidly dividing human medulloblastoma cell line (D283 MED) are shown to express the two high-molecular-weight human neurofilament (NF) subunits, whereas a minority express the low-molecular-weight NF subunit. These three polypep ...
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Journal articleCancer · January 15, 1987
The time course of uptake, retention and clearance of the cationic lipophilic dye, rhodamine 123 (Rh123), within the central nervous system was qualitatively evaluated in rats. Weanling rats were injected intracerebrally with avian sarcoma virus, which ind ...
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Journal articleActa Neuropathol · 1987
Five established cell lines derived from human anaplastic astrocytomas or glioblastoma multiforme were tested for invasiveness into precultured chick heart fragments in vitro. Four of the cell lines (U118 MG, D54 MG, U373 MG and A172) were strongly invasiv ...
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Journal articleActa Cytol · 1987
A panel of monoclonal antibodies was tested immunohistochemically to determine the utility of such reagents in distinguishing among metastatic carcinoma, lymphoma, leukemia and primary brain tumors. The monoclonal antibodies used were: (1) a cocktail compr ...
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Journal articleJ Neurooncol · 1987
Treatment of rats bearing intracranial gliomas induced by the avian sarcoma virus with heparin plus steroid has failed to effectively extend survival time. ...
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Journal articleCancer Genet Cytogenet · January 1987
Karyotypes of four malignant human gliomas were followed from direct preparation and/or short-term culture through their establishment in vitro to determine whether the cultured cells maintained the original karyotypes, or were the products of selection, p ...
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Journal articleJ Neurooncol · 1987
We have examined the impact of methylprednisolone acetate (MPA) on survival of F344 rats that were bearing avian sarcoma virus (ASV)-induced gliomas and that were treated optimally with radiotherapy. Toxicity of MPA (dose range of 0.2-5.0 mg/kg X 7 over 3 ...
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Journal articleJ Neurooncol · 1987
The location, size, geometry and neuropathological findings of anaplastic astrocytomas (AA), gliosarcomas and sarcomas induced by the avian sarcoma virus (ASV) in dogs were compared with images generated using computerized tomography (CT) and real time hig ...
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Journal articleActa Neuropathol · 1987
Karyotypic studies of human gliomas are often limited by a low mitotic index and the appearance of contracted chromosomes that do not exhibit clear banding patterns. The purpose of this study was to investigate the use of hydroxyurea (HU) as a synchronizin ...
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Journal articleNuklearmedizin · December 1986
At the present time, specific imaging and treatment of central nervous system malignancies is not possible. The development of monoclonal hybridoma technology may provide the solution to this problem. We have utilized human glioma-derived cell lines (HGCL) ...
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Journal articleJ Neuroimmunol · December 1986
A glioma-associated antigen was previously identified on an avian sarcoma virus-induced F-344 rat astrocytoma cell line S69-c15 by four rat monoclonal antibodies (7G4, 9F1, 10E3 and 10E7) produced after syngeneic immunization. Earlier data suggested all fo ...
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Journal articleJ Neuroimmunol · December 1986
S69-c15 is a highly immunogenic cell line derived from an avian sarcoma virus (ASV)-induced astrocytoma in F-344 rats. Monoclonal antibody (Mab) production was attempted by fusing F-344 rat splenocytes and mouse P3 X 63/Ag8.653 myeloma cells after a syngen ...
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Journal articleJ Neuropathol Exp Neurol · November 1986
A permanent cell line, S635c15, was derived from an anaplastic astrocytoma induced by the Schmidt-Ruppin strain of avian sarcoma virus (ASV) in a female F-344 rat. Persistent expression of the astrocytic differentiation protein, glial fibrillary acidic pro ...
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Journal articleCancer Res · November 1986
Multiple fusions following immunization of athymic mice with the extensively characterized human glioma cell line D-54 MG resulted in the selection of several antibodies (Mabs) highly reactive with tumors of neuroectodermal origin and unreactive with norma ...
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Journal articleJ Neuropathol Exp Neurol · November 1986
The intermediate filament, glial fibrillary acidic protein (GFAP) has proven to be an important glial marker in diagnostic neuropathology. We report the histochemical application of three monoclonal antibodies (Mab) produced in this laboratory, 1B4, 2E1, a ...
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Journal articleEnviron Health Perspect · September 1986
This report summarizes the results of a workshop on brain tumors in man and animals. Animals, especially rodents are often used as surrogates for man to detect chemicals that have the potential to induce brain tumors in man. Therefore, the workshop was foc ...
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Journal articleCancer Res · June 1986
Seven classical alkylators were tested for activity against the continuous human medulloblastoma cell line TE-671 grown in vitro and as s.c. and intracranial xenografts in athymic mice. Drugs tested included melphalan, cyclophosphamide (4-hydroperoxycyclop ...
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Journal articleCancer Genet Cytogenet · June 1986
Our previous karyotypic studies of malignant human gliomas have demonstrated that their most consistent early or primary gross changes include gains of #7, losses of #10, #22, and the gonosomes, and the presence of double minutes. Karyotypes of 15 addition ...
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Journal articleFEBS Lett · May 26, 1986
The major mono- and disialogangliosides of the extensively characterized established human glioma line D54MG were isolated and purified from subcutaneous solid xenografts grown in athymic (nu/nu) mice. Structural determination showed that they belonged to ...
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Journal articleNeurosurgery · March 1986
We conducted a Phase II study of combination therapy with vincristine and cyclophosphamide in the treatment of patients with recurrent or metastatic medulloblastoma. Fourteen patients were treated with vincristine 2 mg/m2 (2.0-mg maximal dose) by intraveno ...
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Journal articleFood Chem Toxicol · February 1986
Acrylonitrile (ACN) has been tested for carcinogenicity by various routes in a number of rat strains. At relatively high levels of administration (e.g. 500 ppm in the drinking-water) there were statistically significant increases in microscopically detecta ...
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Journal articleJ Neurosurg · February 1986
Current diagnostic and therapeutic modalities for malignant human gliomas are largely nonspecific. The development of monoclonal antibodies (MA's) with their high degree of specificity may allow precise tumor imaging and selective administration of therape ...
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Journal articleActa Neuropathol · 1986
The four permanent human glioma-derived cell lines reported here are the first such lines for which the karyotypes have been followed from the original biopsies through the establishment of the lines in culture. Although ploidy changes were seen, each line ...
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Journal articleCancer Res · January 1986
The continuous human medulloblastoma cell line TE-671 was grown as s.c. and intracranial xenografts in athymic nude mice. Tumor-bearing animals were treated with chemotherapeutic agents at the 10% lethal dose; s.c. xenografts were sensitive to melphalan, 1 ...
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Journal articleAnn Neurol · December 1985
Most vasoactive drugs do not readily penetrate the blood-brain barrier and do not affect cerebral blood flow. We tested the hypothesis that vasoactive drugs may alter blood flow to brain tumors in which the blood-brain barrier is abnormal. Blood flow was m ...
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Journal articleCancer Res · November 1985
Currently numerous clinical trials are in progress utilizing intracarotid (i.c.) 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of malignant gliomas based upon the proposed focal nature of these tumors and the assumption that the i.c. route ...
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Journal articleNeurol Clin · November 1985
Recent progress in brain tumor biology research has helped us to understand the causes of our failure to improve patient survival with current therapeutic approaches. Present combination regimens of surgery, radiotherapy, and chemotherapy fail to address a ...
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Journal articleJ Neuropathol Exp Neurol · November 1985
A new continuous cell line and transplantable xenograft, D283 Med, was derived from the peritoneal implant and ascitic fluid of a child with metastatic medulloblastoma and grew in vitro in suspension culture with spontaneous macroscopic spheroid formation. ...
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Journal articleCancer Research · November 1, 1985
Currently numerous clinical trials are in progress utilizing intracarotid (i.c.) 1,3-bis(2-chloroethyl)-1 -nitrosourea (BCNU) for the treatment of malignant gliomas based upon the proposed focal nature of these tumors and the assumption that the i.e. route ...
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Journal articleJ Neurochem · October 1985
Glutamate analogues have been used in many different experimental approaches in neurobiology. A small number of these analogues have been classified as gliotoxic. We have examined the effect of seven glutamate analogues (five gliotoxic and two neurotoxic) ...
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Journal articleCancer Genet Cytogenet · October 1985
We have karyotyped a human giant cell glioblastoma removed from an 11-year-old girl and have established from it a subcutaneously transplantable line in athymic nude mice. The original tumor contained near-haploid cells with 25 or 26 chromosomes, including ...
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Journal articleCancer Res · September 1985
The human glioma-derived cell line D-54 MG and the human medulloblastoma-derived cell line TE-671 have been shown to be sensitive in culture to the pharmacological interference with glutamine metabolism by acivicin, 6-diazo-5-oxo-L-norleucine, and methioni ...
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Journal articleCancer Res · September 1985
Cellular supply of glutamine, an essential substrate for growth, is derived from extracellular fluid and de novo synthesis. We investigated the relative importance of these sources to the growth of six human anaplastic glioma- and one human medulloblastoma ...
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Journal articleJ Neurosurg · July 1985
The development of monoclonal antibodies has resulted in marked expansion in understanding the central nervous system (CNS). This has been especially true in the study of human neuroectodermal tumors where monoclonal antibodies have been used as physiologi ...
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Journal articleJ Neuroimmunol · June 1985
Both polyclonal and monoclonal antibodies to glial fibrillary acidic protein (GFAP) intensely immunostain the lens epithelium. Two-dimensional gels of mouse lens epithelium protein extracts reveal a protein which co-migrates with GFAP from spinal cord. A l ...
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Journal articleJ Neuropathol Exp Neurol · May 1985
The antigenic heterogeneity of human neuroectodermal tumors defined by both murine and human monoclonal antibodies (MAs) is reported; no patterns of reactivity defining degree of anaplasia, in vitro morphology, or immunogen used were apparent. We investiga ...
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Journal articleJ Neuropathol Exp Neurol · May 1985
Laminin is a basement membrane glycoprotein that is expressed in vitro by immature and neoplastic astrocytes. The expression of laminin in vivo was examined immunohistochemically in normal adult brain and 90 neoplasms of the central and peripheral nervous ...
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Journal articleJ Bacteriol · January 1985
An enzyme active against p-nitrophenyl-beta-D-glucoside was purified from logarithmic-phase cells of Ruminococcus albus cultivated in a medium containing ball-milled cellulose. The purification yielded homogeneous enzyme after an approximately 520-fold inc ...
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Journal articleJ Cell Biochem · 1985
A novel human glioma-associated extracellular matrix (ECM) glycoprotein has been identified by murine monoclonal antibody 81C6. The glycoprotein, designated GMEM, is expressed in the ECM of glioma and mesenchymal cell cultures, in the perivascular matrix o ...
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Journal articleJ Neurooncol · 1985
The extracellular matrix is involved in many aspects of tumor cell biology, including tumor invasion and metastasis. 2A6 and 81C6 are murine monoclonal antibodies that identify glioma-mesenchymal extracellular matrix antigens. The 81C6 antigen is a high mo ...
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Journal articleNeurochem Pathol · 1985
The highly reproducible histochemical localization of glial fibrillary acidic protein (GFAP)+ qualifies it as an important marker of astrocytes in both research and clinical applications. The primary objective of this study was to produce monoclonal antibo ...
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Journal articleJ Neurooncol · 1985
Anaplastic astrocytomas, gliosarcomas and sarcomas were induced in 33 neonatal dogs by intracerebral injection of purified Schmidt-Ruppin strain of avian sarcoma virus (ASV). A total of 11 anaplastic gliomas, 7 gliosarcomas and 18 sarcomas were induced. Te ...
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Journal articleNeurol Res · December 1984
Brain tumours were induced by intracerebral inoculation of beagle puppies with Avian sarcoma virus (ASV) suspension. The inoculation produced solitary or multiple sarcomas in three dogs and intraventricular anaplastic gliomas in four dogs. At the time of t ...
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Journal articleJ Neurosurg · November 1984
Different methods were evaluated for delivering iodine-125 monoclonal antibodies (Mab's) to the central nervous system in 40- to 99-gm Fischer rats. By evaluating interhemispheric, interregional, and brain:blood ratios of Mab's, the efficacy of intracaroti ...
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Journal articleCancer Res · November 1984
An in vitro clonogenic assay was used to test the chemosensitivity of the human medulloblastoma cell line TE-671. Dose-response relationships for reduction in colony formation were generated for cyclophosphamide, vincristine, Adriamycin, 1,3-bis(2-chloroet ...
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Journal articleJ Neuroimmunol · June 1984
Monoclonal antibodies ( MCAs ) have been derived from a fusion of P3-NS1/1-Ag 4-1 (NS1) myeloma cells and splenocytes immunized to human glioma cell line D-54 MG. MCAs 2F3 , 4C7 , and 5B7 were analyzed by cell surface radioimmunoassay (CS-RIA), quantitativ ...
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Journal articleCancer Res · June 1984
We used diaziquone (NSC 182986) alone and in combination with other antineoplastic drugs to treat six human glioma and one human medulloblastoma tumor lines growing s.c. in athymic mice. Pharmacokinetic studies of diaziquone in the plasma of athymic mice i ...
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Journal articleNeurosurgery · April 1984
Despite extensive clinical use of brain tumor chemotherapy via the internal carotid artery (ICA), demonstration of efficacy and toxicity screening of ICA chemotherapy in brain tumor models has been limited. A method for performing ICA injections in 40- to ...
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Journal articleJ Neurosurg · April 1984
Methods for transiently disrupting the blood-brain barrier (BBB) which are consistent with survival are described for immature Fischer 344 rats weighing 40 to 99 gm. A catheter was retrogradely inserted into the external carotid artery to the level of the ...
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Journal articleJ Neurosurg · March 1984
A model was developed for in vivo study of the human glioma-derived D-54 MG cell line in the brains of immunosuppressed Fischer 344 rats. The rats were injected with horse anti-rat thymocyte serum before and after intracerebral inoculation with 5 or 10 mic ...
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Journal articleAnticancer Res · 1984
The murine antiglioma monoclonal antibody 81C6 has been shown to specifically localize in U-251 MG and D-54 MG human glioma subcutaneous and intracranial athymic mouse xenografts expressing the human gliomamesenchymal extracellular matrix glycoprotein GMEM ...
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Journal articleClin Neuropathol · 1984
Malignant gliomas constitute a morphologically diverse group of neoplasms that respond poorly to therapy. The median survival of patients with glioblastoma multiforme, the most common malignant glioma, is only 11 months. Several factors influence the thera ...
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Journal articleAnn Neurol · 1984
Carbon-11-labeled dimethyloxazolidinedione ([11C]DMO) was injected intravenously into human subjects, and serial positron emission tomographic (PET) scans were obtained until brain-blood equilibration was achieved or could be accurately predicted from dyna ...
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Journal articleCancer Genet Cytogenet · December 1983
Four permanent cell lines derived from malignant human gliomas were karyotyped using Giemsa-trypsin banding. D-65 MG had a stemline with 44 chromosomes, including 11 markers: 1p+, 2q-, 3p-, 3q+, 4p-, 9q-, 11q+, 15q-, 17p+, 21p+, 22q-. The net effect after ...
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Journal articleJ Neuropathol Exp Neurol · September 1983
A model was developed for the in vitro and in vivo study of the continuous cell line, TE-671, derived from a human medulloblastoma. TE-671 grew in vitro as sheets of uniform triangular- to spindle-shaped cells with round to oval nuclei and sparse cytoplasm ...
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Journal articleCancer Treat Rep · September 1983
Five human glioma tumor lines were transplanted subcutaneously in athymic nude mice. Three of the lines (D-54 MG, U-118 MG, and U-251 MG) were derived from permanent human glioma cell lines, while the other two lines (N-456 and N-519) were established as d ...
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Journal articleJ Neurosurg · August 1983
Twenty patients with malignant gliomas were selected for active immunization within 4 weeks following surgery. Each patient had a Karnofsky Functional Rating equal to or greater than 70, a peripheral blood lymphocyte count equal to or greater than 1000 cel ...
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Journal articleJ Neurosurg · August 1983
Serial serological studies were carried out on 19 of 20 patients with malignant gliomas who were actively immunized with one of two human glioma tissue culture cell lines (D-54MG or U-251MG). Most patients mounted a significant serum reaction to histocompa ...
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Journal articleCancer Res · July 1983
The human medulloblastoma cell line TE-671 was grown s.c. and intracranially in athymic nude mice. Tumor-bearing animals treated with chemotherapeutic agents or radiation were compared to untreated tumor-bearing controls. Tumors growing s.c. were sensitive ...
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Journal articleCancer Res · July 1983
We have investigated the antigenic heterogeneity of human glioma cells and its correlation with other parameters of tumor cell heterogeneity (karyotype, 2':3' cyclic nucleotide 3'-phosphohydrolase expression, in vitro morphology) using the established huma ...
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Journal articleCancer Res · July 1983
Regional measurements of blood-to-tissue transport were performed in transplanted RG-2 rat gliomas using [alpha- 14C]aminoisobutyric acid (AIB), quantitative autoradiography, and equations to express a unidirectional transfer constant. Thirty-eight intracr ...
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Journal articleCancer Res · July 1983
Regional measurements of blood flow (F) were performed in transplanted intracerebral RG-2 rat gliomas using [14C]iodoantipyrine, Kety-Schmidt blood flow equations, and quantitative autoradiography. Twenty-nine intracranial tumors in ten rats were analyzed ...
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Journal articleCancer Res · June 1983
The distribution and localization of a glioma-associated antigen defined by monoclonal antibody 81C6 has been examined using human cultured cell lines and tissues. Monoclonal antibody 81C6 was selected from a hybridoma fusion of spleen cells of mice immuni ...
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Journal articleNeurosurgery · June 1983
Tumors derived from the established human glioma cell line D-54 MG were transplanted intracerebrally into athymic "nude" mice. All control mice developed tumors in the brain after the transplantation of 10(5) cells and died within 30 days. Tumor was purely ...
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Journal articleNeurology · June 1983
Regional blood flow (F) was measured in avian sarcoma virus (ASV)-induced brain tumors in rats. Blood flow was variable in individual as well as different tumors; tumor F did not correlate with histologic classification, tumor size, central versus peripher ...
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Journal articleNeurology · June 1983
Regional blood-to-tissue transport of 14C-alpha-aminoisobutyric acid (AIB) was measured in avian sarcoma virus (ASV)-induced rat brain tumors and expressed as a unidirectional transfer rate constant (K). The magnitude of K was variable and did not correlat ...
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Journal articleSurg Neurol · May 1983
Bacillus Calmette-Guerin cell-wall preparation was injected along with avian sarcoma virus in the brains of newborn Fischer 344 rats, and subsequent glioma induction was compared with rats injected with avian sarcoma virus alone. The percentage of glioma i ...
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Journal articleJ Neurochem · February 1983
A continuous human glioma cell line grown in culture and as a solid tumor was analyzed for glial fibrillary acidic (GFA) protein. This material provided a rich source for GFA protein that could also be manipulated and controlled. Immunoperoxidase staining ...
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Journal articleCancer Res · February 1983
We studied the regional distribution of proliferating tumor cells in five avian sarcoma virus-induced gliomas. The labeling index and spatial distribution of [3H]thymidine (dThd)-labeled tumor cells were determined in serial sections of each tumor with a c ...
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Journal articleJ Neurooncol · 1983
Sixteen of 17 anaplastic human gliomas (AHGs) transplanted into athymic mice produced progressively growing subcutaneous nodules at the site of implantation. Thirty-four of 68 animals (50%) receiving transplanted tissue developed 500 m3 tumors in 24 to 364 ...
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Journal articleJ Neuropathol Exp Neurol · January 1983
Messenger RNA (mRNA) extracted from a continuous human glioma cell line grown in culture or as a solid tumor was translated in an mRNA-dependent reticulocyte lysate system. Translation products labeled with [35S]methionine were immunoprecipitated with anti ...
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Journal articleJ Neuropathol Exp Neurol · September 1982
The sarcomatous components of most glioma-sarcomas are thought to arise from the neoplastic transformation of hyperplastic endothelial and adventitial vascular cells in a preexisting glioblastoma multiforme. The expression of factor VIII/von Willebrand fac ...
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Journal articleJ Neuroimmunol · August 1982
The antigenic relationship between human tumors of neuroectodermal origin and fetal brain were further investigated by characterization of two hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NSI) myeloma cells and splenocytes hyperimmunized ...
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Journal articleProc Natl Acad Sci U S A · July 1982
The effect of adrenal cortical steroids and osmotic blood-brain barrier modification on methotrexate delivery to normal and glioma-bearing rats was studied. In animals with the avian sarcoma virus-induced glioma, osmotic blood-brain barrier modification re ...
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Journal articleJ Neuroimmunol · June 1982
Lewis rats bearing avian sarcoma virus (ASV)-induced brain tumors were injected with guinea pig spinal cord emulsion and complete Freund's Adjuvant to determine if they remained susceptible to induction of experimental allergic encephalomyelitis (EAE). The ...
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Journal articleJ Histochem Cytochem · April 1982
The immunohistochemical detection of factor VIII/von Willebrand factor antigen (FVIII/vWF-AG) in formalin-fixed paraffin-embedded tissues was investigated using the peroxidase-antiperoxidase (PAP) method. Highly purified human FVIII/vWF was used to raise r ...
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Journal articleJ Neuropathol Exp Neurol · March 1982
The permeability of different brain tumor models to horseradish peroxidase (HRP) was examined by determining the fraction of tumor that contained HRP after intravenous administration. The intracerebral tumor models studied were Avian Sarcoma Virus (ASV)-in ...
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Journal articleCancer Res · January 1982
The antigenic relationships between human tumors of neuroectodermal origin and fetal brain were investigated by the production of hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NS1) myeloma cells with splenocytes from a mouse multiply immun ...
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Journal articleCancer Treat Rep · January 1982
Using the avian sarcoma virus (ASV) rat glioma model, we have evaluated the in vivo effectiveness of two lipid-soluble folate antagonists, metoprine (DDMP) and its 6-ethyl analog etoprine. When adult Fischer 344 rats, which were previously inoculated with ...
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Journal articleActa Neuropathol · 1982
The histogenesis of hemangioblastoma stromal cells is unresolved. Ultrastructural observations suggest that the stromal cells, endothelial cells, and pericytes that compose this neoplasm are all derived from angiogenic mesenchyme. The expression of factor ...
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Journal articleAm J Pathol · December 1981
The morphologic and biochemical characteristics of human surgical biopsy specimens taken from 17 patients with anaplastic human gliomas and of athymic mouse-grown tumors derived from them were examined. Fourteen were categorized as glioblastoma multiforme, ...
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Journal articleJ Neurosurg · October 1981
The mitogenic responsiveness of peripheral blood lymphocytes obtained from Fischer 344 rats inoculated with avian sarcoma virus was studied. In addition, quantitative alterations in lymphocyte subpopulations were determined in these animals. Only periphera ...
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Journal articleJ Neuroimmunol · September 1981
The efficacy and non-toxicity of BCG-cell wall preparation (BCG-CW) + cultured human glioma-derived cells as immunogen in non-human primates (Macaca fascicularis) were investigated to determine the optimal conditions for immunization without induction of e ...
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Journal articleJ Comput Assist Tomogr · August 1981
Seven neonatal dogs were inoculated intracerebrally with Avian Sarcoma Virus (ASV) and studied by computed tomography (CT) for intracranial tumors. The tumor yield was five anaplastic astrocytomas and two sarcomas, with an average latency of 57 days. Compu ...
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Journal articleJ Neuropathol Exp Neurol · July 1981
Fifteen permanent cell lines derived from human gliomas were subcutaneously transplanted into athymic nude mice (nu/nu genotype, NIH Swiss and BALB/c backgrounds). Four were tumorigenic. Three of the four (D-54 MG, U-118 MG, and U-251 MG) produced progress ...
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Journal articleJ Neuropathol Exp Neurol · July 1981
Fifteen permanent cell lines derived from human gliomas which are individually distinct by immunologic and biochemical criteria were evaluated to determine if morphologic or cell biologic parameters distinguished the 4 lines which were tumorigenic in athym ...
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Journal articleJ Neuropathol Exp Neurol · May 1981
The addition of exogenous cyclic nucleotides to cultured neoplastic cells has been reported by others to cause changes in growth properties and cellular morphology. We have studied the in vitro morphologic response to exogeneous dibutyryl adenosine 3':5'-c ...
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Journal articleJ Neuropathol Exp Neurol · May 1981
Six new permanent cell lines were established from human gliomas and compared to nine other cell lines from human gliomas. All fifteen lines had individually distinct HLA phenotypes and all but two, which were from a black patient, had type B glucose-6-pho ...
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Journal articleAm J Pathol · May 1981
Factor VIII/von Willebrand factor (FVIII/vWF), a glycoprotein molecular complex found in human plasma, has been demonstrated by cell membrane fluorescence to be present on the surface of cultured human umbilical cord vein endothelial cells. The endothelial ...
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Journal articleJournal of Computer Assisted Tomography · January 1, 1981
Seven neonatal dogs were inoculated intracerebrally with Avian Sarcoma Virus (ASV) and studied by computed tomography (CT) for intracranial tumors. The tumor yield was five anaplastic astrocytomas and two sarcomas, with an average latency of 57 days. Compu ...
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Journal articleCancer Treat Rep · 1981
Seven different experimental glioma models were studied to determine their capillary permeability to horseradish peroxidase. The models were the autochthonous ASV-viral model, intracerebral (ic) and (sc) injections of rat 9L and RG-2 tumor cell lines, the ...
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Journal articleJ Neurosurg · July 1980
The avian sarcoma virus-induced glioma model in rats was used to evaluate radiation dose response (survival curves), giving fractionated treatments to the whole head. Groups of 14 to 20 rats received total doses of 2300, 4600, or 5750 rads over 2, 4, or 5 ...
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Journal articleNeurology · March 1980
Autochthonous gliomas were induced in rats by intracerebral inoculation of avian of avian sarcoma virus and studied by 3H-thymidine autoradiography. Parenchymal glial tumor cells had a 3H-labeling index (LI) of 3.0 to 13.6%. Endothelial cells in tumor bloo ...
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Journal articleActa Neuropathol · 1980
One of the few spontaneous gliomas in inbred animals, the VM/Dk spontaneous murine astrocytoma (SMA), has seen limited use. Previously restricted to an in vivo system, the SMA was only transplantable intracerebrally (IC) using nonquantifiable suspensions o ...
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Journal articleAmerican Journal of Pathology · January 1, 1980
Several facts are now clearly established about immunity and human gliomas. The cause of at least some gliomas can be recognized. Glioma patients at the time of diagnosis can be stratified in terms of immune responsiveness, from those who are severely depr ...
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Journal articleCancer Immunology Immunotherapy · January 1, 1980
Five-day-old Fischer 344 rats were inoculated intracerebrally with BCG cell walls attached to oil (BCG-CW) or with oil emulsion alone. Doses of BCG-CW of 40 μg in 0.01 ml, 200 μg in 0.05 ml, and 400 μg in 0.1 ml were used, with similar volumes of oil emuls ...
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Journal articleJ Neurosurg · November 1979
The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarrcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU wa ...
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Journal articleNeurosurgery · April 1979
Surgical biopsies from 2 human craniopharyngiomas were transplanted subcutaneously into 6 athymic "nude" mice. Morphologically characteristic craniopharyngiomas grew in 5 of these animals. In 4 animals growth was sufficient to allow transplantation into a ...
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Journal articleCancer Res · February 1979
Dihydrofolate reductase (DHFR) was measured during the development in rats of brain tumors induced following inoculation with avian sarcoma virus. Increasing activity of this enzyme in brain was correlated with the course of primary brain tumor growth. The ...
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Journal articleCancer Research · February 1, 1979
Dihydrofolate reductase (DHFR) was measured during the development in rats of brain tumors induced following inoculation with avian sarcoma virus. Increasing activity of this enzyme in brain was correlated with the course of primary brain tumor growth. The ...
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Journal articleActa Cytol · 1979
Five permanent cell lines derived from human gliomas were examined at 24-hour intervals to determine optimal phases of their population growth curves for comparative morphologic studies. In early exponential growth phase, individual cytologic criteria were ...
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Journal articleActa Neuropathol · January 19, 1978
Intracerebral inoculation of avian sarcoma virus (ASV) in postnatal animals induces gliomas and sarcomas but no neuronal tumors. High titer Bratislava-77 strain ASV was inoculated intracerebrally in fetal F-344 rats between 17 and 20 days of gestation: a t ...
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Journal articleCancer Res · January 1978
The mitogenic responsiveness of spleen cells obtained from avian sarcoma virus-inoculated Fischer 344 rats was studied. Sixty % of the rats had astrocytomas, 13% had sarcomas, 7% had mixed gliosarcomas, and 20% had no evidence of tumors. Only spleen cells ...
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Journal articleCancer Res · December 1977
The surface antigenic characteristics of human glial brain tumor (HGBT) cells were studied by complement-dependent cytotoxic antibody assays and indirect membrane immunofluorescence. Eight permanent, well-characterized cell lines derived from human gliomas ...
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Journal articleActa Neuropathol · September 26, 1977
We have studied the sequential morphological events of glial tumorigenesis in neonatal dogs, using high titer subgroup C Bratislava-77 Avian Sarcoma Virus, given as 0.01 ml by intraventricular inoculation. The cells of the subependymal plate are those whic ...
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Journal articleAm J Pathol · July 1977
Nontumorigenic rat cells and their tumorigenic counterparts were studied with scanning electron microscopy under controlled conditions in vitro and with transmission electron microscopy after replantation in vivo to discern if external morphology reflected ...
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Journal articleJ Neurosurg · July 1977
The avian sarcoma virus-induced glioma model in rats was used to study the effectiveness of immunotherapy, namely, Bacillus Calmette-Guérin (BCG) with or without sarcoma cells and/or chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), upon surv ...
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Journal articleCancer Res · June 1977
Intracranial neoplasms were induced by intracerebral inoculation of a standardized, cell-free inoculum of the Bratislava-77 strain of avian sarcoma virus in F344 rats at 1, 9,97 to 99, and 528 days of age. Deaths from diseases that occur spontaneously in a ...
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Journal articleActa Neuropathol · April 29, 1977
F-344 rats were inoculated intracerebrally at 1 and at 133 days of age with the Bratislava-77 strain of avian sarcoma virus. Groups of rats were sequentially sacrificed following inoculation so that early stages of microtumor formation could be evaluated. ...
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Journal articleJ Neurosurg · April 1977
Cellular and humoral immune parameters were evaluated in a series of brain-tumor patients, 42 with glioblastoma multiforme, 17 with other anaplastic gliomas, and 17 with meningiomas. A degree of anergy was found, which seems in the group as a whole to be p ...
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Journal articleCancer Res · March 1977
The specificity of a single rabbit antiserum pool raised against the purified major glycoprotein, gp71, of Friend murine leukemia virus was determined for a variety of virus-producing mouse, feline, and gibbon ape cell lines by viable cell membrane immunof ...
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Journal articleCancer Res · March 1977
The expression of the major glycoprotein, gp71, of murine leukemia virus was studied on the surfaces of a variety of normal murine cell lines with a monospecific rabbit antiserum raised against purified Friend murine leukemia virus gp71. Using viable cell ...
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Journal articleJ Clin Microbiol · January 1977
A microtechnique for an indirect viable-cell membrane immunofluorescence titration assay was developed using Friend murine leukemia virus (F-MuLV)-producing cells and monospecific rabbit antisera to F-MuLV structural antigens. The assay was sensitive and d ...
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Journal articleJournal of Neurosurgery · January 1, 1977
The authors provide a summary of a workshop on 'Cancer of the Brain'. This conference reviewed the current knowledge about the etiology and pathogenesis of human brain tumors and the experimental induction of comparable animal brain tumors, and considered ...
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Journal articleJournal of Neurosurgery · 1977
The avian sarcoma virus-induced glioma model in rats was used to study the effectiveness of immunotherapy, namely, Bacillus Calmette-Guerin (BCG) with or without sarcoma cells and/or chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), upon surv ...
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Journal articleJ Natl Cancer Inst · June 1976
Rats bearing primary tumors of the brain induced by avian sarcoma virus (ASV) were studied with the migration-inhibition factor (MIF) assay for the presence of cell-mediated immunity to tumor-associated antigens. Astrocytomas and sarcomas of the brain were ...
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Journal articleJ Natl Cancer Inst · June 1976
An indirect radioimmunoassay was developed for the sequential adsorption analysis of rabbit antibodies raised against rat neuroectodermal cells. The quantitativee relationship between primary adsorbed rabbit antitumor antibodies and secondary adsorbed goat ...
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Journal articleAm J Pathol · April 1976
Groups of F-344 rats were inoculated with the Bratislava-77 strain of avian sarcoma virus (B-77 ASV) within 24 hours of birth, at 9 days of age, or between 97 and 119 days of age. Intracranial tumors developed in each age group. Multiple tumors with mixed ...
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Journal articleFederation Proceedings · January 1, 1976
RNA C type viruses are oncogenic agents in many animal species and in particular are associated with all types of murine leukemia. The expression of the major glycoprotein, gp71, of murine leukemia virus, in which virus neutralizing and type specific deter ...
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Journal articleJ Neuropathol Exp Neurol · July 1975
The induction of intracranial neoplasms following the intracerebral inoculation of avian sarcoma virus (ASV) in neonatal mammals is well established. The present study demonstrates the susceptibility of adult rats and compares the incidence and morphology ...
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Journal articleJ Natl Cancer Inst · June 1975
Morphologically distinct virus-like particles (VLP), similar to R-type VLP, were observed by electron microscopy in experimental rat central nervous system tumors induced with the B-77-C strain of avian sarcoma virus (ASV). R-type VLP have a characteristic ...
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Journal articleProc Natl Acad Sci U S A · December 1974
Cultured cells of different chemically-induced C57BL/6N murine sarcomas produced variable amounts of infectious murine leukemia virus (MuLV) and contained proportional amounts of MuLV structural components as determined by radioimmunoassay. Monospecific an ...
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Journal articleAppl Microbiol · July 1974
Improved techniques consisting of glutaraldehyde fixation, Giemsa staining, and colony counter enumeration of foci in viral infectivity assays were compared to microscope scanning and lantern slide projection methods. These techniques broadened the scope o ...
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