Journal articleJ Immunother Cancer · March 24, 2026
BACKGROUND: Glioblastoma (GBM) remains uniformly lethal due to pronounced intratumoral heterogeneity and a highly immunosuppressive microenvironment that limits the efficacy of targeted therapies. METHODS: We engineered chimeric antigen receptor (CAR) T ce ...
Full textLink to itemCite
Journal articleJAMA Netw Open · November 3, 2025
IMPORTANCE: Proton pump inhibitors (PPI) are often prescribed to prevent steroid-induced gastritis and peptic ulcer disease in patients with glioblastoma. Yet, these drugs may enhance the activity of aldehyde dehydrogenase 1 A1 (ALDH1A1), which has been li ...
Full textLink to itemCite
Journal articleSci Rep · October 23, 2025
Many cancers evade immunosurveillance by downregulating surface major histocompatibility class (MHC)-I. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes MHC-I degradation and is elevated in glioma. Evolocumab is a clinically approved PCSK9 in ...
Full textOpen AccessLink to itemCite
Journal articleNat Cancer · September 2025
The human cytomegalovirus (CMV) antigen pp65 is expressed in high-grade glioma (HGG) and medulloblastoma but not in the adjacent brain. This single-arm phase 1 trial ( NCT03299309 ) assessed the safety and immunogenicity of a peptide vaccine (PEP-CMV) targ ...
Full textOpen AccessLink to itemCite
Journal articleJ Clin Invest · June 16, 2025
The efficacy of T cell-activating therapies against glioma is limited by an immunosuppressive tumor microenvironment and tumor-induced T cell sequestration. We investigated whether peripherally infused nonantigen specific autologous lymphocytes could accum ...
Full textLink to itemCite
Journal articleWorld Neurosurg · December 2023
OBJECTIVE: Preoperative assessment is important for neurosurgical risk stratification, but the level of evidence for individual screening tests is low. In preoperative urinalysis (UA), testing may significantly increase costs and lead to inappropriate anti ...
Full textLink to itemCite
Journal articleNat Cancer · September 2023
The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, ...
Full textLink to itemCite
Journal articleBioDrugs · July 2023
Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and ...
Full textLink to itemCite
Journal articleNeuro Oncol · June 2, 2023
BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with po ...
Full textLink to itemCite
Journal articleAdv Radiat Oncol · 2023
PURPOSE: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-S ...
Full textLink to itemCite
Journal articleFront Immunol · 2023
Chimeric antigen receptor (CAR) T cell therapy in glioblastoma faces many challenges including insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, preclinical studies evaluating CAR T cells in glioblastoma f ...
Full textLink to itemCite
Journal articleAnesth Analg · December 1, 2022
BACKGROUND: Early hypotension after severe traumatic brain injury (sTBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors, commonly norepinephrine and phenylephrine, to suppo ...
Full textOpen AccessLink to itemCite
Journal articleNat Commun · October 29, 2022
Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly ex ...
Full textLink to itemCite
Journal articleNeurosurgery · September 1, 2022
BACKGROUND: Extracranial multisystem organ failure is a common sequela of severe traumatic brain injury (TBI). Risk factors for developing circulatory shock and long-term functional outcomes of this patient subset are poorly understood. OBJECTIVE: To ident ...
Full textOpen AccessLink to itemCite
Journal articleSci Adv · July 22, 2022
Subunit vaccines inducing antibodies against tumor-specific antigens have yet to be clinically successful. Here, we use a supramolecular α-helical peptide nanofiber approach to design epitope-specific vaccines raising simultaneous B cell, CD8+ T cell, and ...
Full textLink to itemCite
Journal articleNeurocrit Care · April 2022
BACKGROUND: The aim of this study was to describe the utilization patterns of brain tissue oxygen (PbtO2) monitoring following severe traumatic brain injury (TBI) and determine associations with mortality, health care use, and pulmonary toxicity. METHODS: ...
Full textOpen AccessLink to itemCite
Journal articleClin Cancer Res · February 15, 2022
Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highl ...
Full textLink to itemCite
Journal articleClin Cancer Res · February 15, 2022
Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for N ...
Full textLink to itemCite
Journal articleNeurocrit Care · February 2022
BACKGROUND: Early hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following T ...
Full textOpen AccessLink to itemCite
Journal articleMethods Mol Biol · 2022
Our group has employed methodologies for effective ex vivo generation of dendritic cell (DC) vaccines for patients with primary malignant brain tumors. In order to reliably produce the most potent, most representational vaccinated DC that will engender an ...
Full textLink to itemCite
Journal articleNeurooncol Adv · 2022
BACKGROUND: The phase 1 cohorts (1c+1d) of CheckMate 143 (NCT02017717) evaluated the safety/tolerability and efficacy of nivolumab plus radiotherapy (RT) ± temozolomide (TMZ) in newly diagnosed glioblastoma. METHODS: In total, 136 patients were enrolled. I ...
Full textLink to itemCite
Journal articleJ Immunol Methods · December 2021
Here we present a 14-color flow cytometry panel for the evaluation of 13 myeloid and lymphoid populations within murine glioblastoma samples. Reagents, processing protocols, and downstream analyses were thoroughly validated and optimized to resolve the fol ...
Full textLink to itemCite
Journal articleJ Immunother Cancer · November 2021
Glioblastoma is the the most common primary brain tumor in adults. Onset of disease is followed by a uniformly lethal prognosis and dismal overall survival. While immunotherapies have revolutionized treatment in other difficult-to-treat cancers, these have ...
Full textLink to itemCite
Journal articleCancers (Basel) · October 26, 2021
Glioblastoma is an immunologically 'cold' tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While man ...
Full textLink to itemCite
Journal articleNeurocrit Care · October 2021
BACKGROUND/OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of morbidity, mortality, and disability in the USA. While cardiopulmonary dysfunction can result in poor outcomes following severe TBI, the impact of acute kidney injury (AKI) is poorly ...
Full textOpen AccessLink to itemCite
Journal articleCrit Care Med · October 1, 2021
OBJECTIVES: Traumatic brain injury is a leading cause of death and disability in the United States. While the impact of early multiple organ dysfunction syndrome has been studied in many critical care paradigms, the clinical impact of early multiple organ ...
Full textOpen AccessLink to itemCite
Journal articleClin Cancer Res · July 15, 2021
PURPOSE: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in ...
Full textLink to itemCite
Journal articleNPJ Vaccines · January 18, 2021
Personalized cancer vaccines targeting neoantigens arising from somatic missense mutations are currently being evaluated for the treatment of various cancers due to their potential to elicit a multivalent, tumor-specific immune response. Several cancers ex ...
Full textOpen AccessLink to itemCite
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 ...
Full textOpen AccessLink to itemCite
Journal articleJ Neurooncol · January 2021
INTRODUCTION: Glioblastoma (GBM) has a survival rate of around 2 years with aggressive current standard of care. While other tumors have responded favorably to trials combining immunotherapy and chemotherapy, GBM remains uniformly deadly with minimal incre ...
Full textLink to itemCite
Journal articleFront Oncol · 2021
We have only recently begun to understand how cancer metabolism affects antitumor responses and immunotherapy outcomes. Certain immunometabolic targets have been actively pursued in other tumor types, however, glioblastoma research has been slow to exploit ...
Full textLink to itemCite
Journal articleAdv Radiat Oncol · 2021
PURPOSE: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. METHODS AND MATERIALS: Adult patients with 4 to 10 brain metastases ...
Full textLink to itemCite
Journal articleClin Cancer Res · October 15, 2020
Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy and especially immune checkpoint ...
Full textLink to itemCite
Journal articleClin Cancer Res · October 15, 2020
Despite standard of care for glioblastoma, including gross total resection, high-dose radiation, and dose-limited chemotherapy, this tumor remains one of the most aggressive and therapeutically challenging. The relatively small number of patients with this ...
Full textLink to itemCite
Journal articleExpert Rev Clin Pharmacol · October 2020
INTRODUCTION: Despite maximal surgical resection and chemoradiation, glioblastoma (GBM) continues to be associated with significant morbidity and mortality. Novel therapeutic strategies are urgently needed. Given success in treating multiple other forms of ...
Full textLink to itemCite
Journal articlePharmaceutics · September 1, 2020
Intra‐parenchymal injection and delivery of therapeutic agents have been used in clinical trials for brain cancer and other neurodegenerative diseases. The complexity of transport pathways in tissue makes it difficult to envision therapeutic agent distribu ...
Full textCite
Journal articleJAMA Oncol · July 1, 2020
IMPORTANCE: Clinical outcomes for glioblastoma remain poor. Treatment with immune checkpoint blockade has shown benefits in many cancer types. To our knowledge, data from a randomized phase 3 clinical trial evaluating a programmed death-1 (PD-1) inhibitor ...
Full textLink to itemCite
Journal articleNat Commun · June 24, 2020
The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test ...
Full textLink to itemCite
Journal articleBiomater Sci · June 21, 2020
Several different self-assembling peptide systems that form nanofibers have been investigated as vaccine platforms, but design principles for adjusting the character of the immune responses they raise have yet to be well articulated. Here we compared the i ...
Full textLink to itemCite
Journal articleExpert Opin Biol Ther · June 2020
Introduction: Glioblastoma (GBM) is a highly aggressive brain tumor and is one of the most lethal human cancers. Chimeric antigen receptor (CAR) T cell therapy has markedly improved survival in previously incurable disease; however, this vanguard treatment ...
Full textLink to itemCite
Journal articleCancer · April 1, 2020
Brain metastasis (BM), the most common adult brain tumor, develops in 20% to 40% of patients with late-stage cancer and traditionally are associated with a poor prognosis. The management of patients with BM has become increasingly complex because of new an ...
Full textLink to itemCite
Journal articleClin Cancer Res · April 1, 2020
PURPOSE: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblas ...
Full textLink to itemCite
Journal articleJ Immunother Cancer · April 2020
BACKGROUND: First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with ...
Full textLink to itemCite
Journal articleThe Journal of clinical investigation · February 2020
Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, sugg ...
Full textCite
Journal articleNat Rev Cancer · January 2020
Gliomas, the most common malignant primary brain tumours, remain universally lethal. Yet, seminal discoveries in the past 5 years have clarified the anatomy, genetics and function of the immune system within the central nervous system (CNS) and altered the ...
Full textLink to itemCite
Journal articlePLoS One · 2020
We recently reported the development of a fully-human, CD3-binding bispecific antibody for immunotherapy of malignant glioma. To translate this therapeutic (hEGFRvIII-CD3- bi-scFv) to clinical trials and to help further the translation of other similar CD3 ...
Full textLink to itemCite
Journal articleClin Cancer Res · November 15, 2019
The incidence of brain metastases is increasing as cancer therapies improve and patients live longer, providing new challenges to the multidisciplinary teams that care for these patients. Brain metastatic cancer cells possess unique characteristics that al ...
Full textLink to itemCite
Journal articleJournal of neurosurgery · September 2019
The last decade has seen a crescendo of FDA approvals for immunotherapies against solid tumors, yet glioblastoma remains a prominent holdout. Despite more than 4 decades of work with a wide range of immunotherapeutic modalities targeting glioblastoma, effi ...
Full textCite
Journal articleJ Proteome Res · August 2, 2019
Bispecific single chain antibody fragments (bi-scFv) represent an emerging class of biotherapeutics. We recently developed a fully human bi-scFv (EGFRvIII:CD3 bi-scFv) with the goal of redirecting CD3-expressing T cells to recognize and destroy malignant, ...
Full textLink to itemCite
Journal articleNat Rev Clin Oncol · August 2019
Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properti ...
Full textLink to itemCite
Journal articleClin Cancer Res · July 15, 2019
Glioblastoma (GBM) is a highly lethal brain tumor with poor responses to immunotherapies that have been successful in more immunogenic cancers with less immunosuppressive tumor microenvironments (TME). The GBM TME is uniquely challenging to treat due to tu ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articlePharmacol Ther · May 2019
Several Phase II and III clinical trials have demonstrated that immunotherapy can induce objective responses in otherwise refractory malignancies in tumors outside the central nervous system. In large part, effector T cells mediate much of the antitumor ef ...
Full textLink to itemCite
Journal articleClin Cancer Res · April 1, 2019
Glioblastoma (GBM) is a devastating disease with an extremely poor prognosis. Immunotherapy via adoptive cell transfer (ACT), especially with T cells engineered to express chimeric antigen receptors (CAR), represents a particularly promising approach. Desp ...
Full textLink to itemCite
Journal articleHealth Sci Rep · April 2019
BACKGROUND AND AIMS: This retrospective review of patients with recurrent glioblastoma treated at the Preston Robert Tisch Brain Tumor Center investigated treatment patterns, survival, and safety with bevacizumab in a real-world setting. METHODS: Adult pat ...
Full textLink to itemCite
Journal articleNat Med · March 2019
In the version of this article originally published, the figure callout in this sentence was incorrect: "Furthermore, in S1P1-KI mice themselves, whereas PD-1 blockade was ineffectual as monotherapy, the effects of 4-1BB agonism and checkpoint blockade pro ...
Full textLink to itemCite
Journal articleClin Cancer Res · January 1, 2019
PURPOSE: Chimeric antigen receptor (CAR) T cells have shown promise against solid tumors, but their efficacy has been limited, due in part, to immunosuppression by CD4+FoxP3+ regulatory T cells (Tregs). Although lymphodepletion is commonly used to deplete ...
Full textLink to itemCite
Journal articleNeurosurgery · December 1, 2018
BACKGROUND: Despite increasing emphasis on quality improvement in neurosurgery, few studies have evaluated the impact of quality initiatives on health-assessment metrics including risk of mortality (ROM), severity of illness (SOI), case mix index (CMI), an ...
Full textLink to itemCite
Journal articleJ Clin Neurosci · October 2018
Convection Enhanced Delivery (CED) infuses therapeutic agents directly into the intracranial area continuously under pressure. The convection improves the distribution of therapeutics such as those aimed at brain tumors. Although CED successfully delivers ...
Full textLink to itemCite
Journal articleNat Med · September 2018
T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment- ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Immunol Methods · August 2018
The ELISpot assay prevails as one of the most sensitive and meaningful assays for the detection of antigen-specific, effector immune responses. Acquisition of cellular analyte for ELISpot analysis is typically not problematic when derived from tissues enri ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeuro Oncol · April 9, 2018
BACKGROUND: Immunotherapies have demonstrated efficacy across a diverse set of tumors supporting further evaluation in glioblastoma. The objective of this study was to evaluate the safety/tolerability and describe immune-mediated effects of nivolumab ± ipi ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleOncoimmunology · 2018
Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is an effective immunotherapy for B-cell malignancies but has failed in some solid tumors clinically. Intracerebral tumors may pose challenges that are even more significant. In orde ...
Full textOpen AccessLink to itemCite
Journal articleOncoimmunology · 2018
Despite their promise, tumor-specific peptide vaccines have limited efficacy. CD27 is a costimulatory molecule expressed on CD4+ and CD8+ T cells that is important in immune activation. Here we determine if a novel CD27 agonist antibody (αhCD27) can enhanc ...
Full textLink to itemCite
Journal articleACS Biomater Sci Eng · December 11, 2017
A supramolecular peptide vaccine system was designed in which epitope-bearing peptides self-assemble into elongated nanofibers composed almost entirely of alpha-helical structure. The nanofibers were readily internalized by antigen presenting cells and pro ...
Full textLink to itemCite
Journal articleExpert Rev Clin Immunol · November 2017
Immunotherapy embodies any approach that manipulates the immune system for therapeutic benefit. In this regard, various clinical trials have employed direct vaccination with patient-specific dendritic cells or adoptive T cell therapy to target highly aggre ...
Full textLink to itemCite
Journal articleChinese Neurosurgical Journal · October 3, 2017
Background: While the optimal combination of whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) and surgical resection in the treatment of brain metastases, is controversial, the addition of SRS to surgical resction of solitary metastasis may ...
Full textCite
Journal articleNeuro Oncol · October 1, 2017
BACKGROUND: Stereotactic radiosurgery (SRS) offers excellent local control for brain metastases (BM) with low rates of toxicity. Radiation necrosis (RN) may occur after treatment and is challenging to distinguish from local recurrence (LR). We evaluated en ...
Full textLink to itemCite
Journal articleWorld Neurosurg · October 2017
OBJECTIVE: To evaluate accuracy of a computed tomography (CT)-guided frameless stereotactic drilling and catheter system. METHODS: A prospective, single-arm study was performed using human cadaver heads to evaluate placement accuracy of a novel, flexible i ...
Full textLink to itemCite
Journal articleLancet Oncol · October 2017
BACKGROUND: Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the additio ...
Full textLink to itemCite
Journal articleJ Clin Oncol · July 20, 2017
Glioblastoma (GBM) is the most lethal form of brain tumor and remains a large, unmet medical need. This review focuses on recent advances in the neurosciences that converge with the broader field of immuno-oncology. Recent findings in neuroanatomy provide ...
Full textLink to itemCite
Journal articleCurr Opin Neurol · June 2017
PURPOSE OF REVIEW: Immunotherapy has emerged as a cornerstone of modern oncology with regulatory approvals for a variety of immunotherapeutics being achieved for a spectrum of cancer indications. Nonetheless the role of these approaches for patients with g ...
Full textLink to itemCite
Journal articleNat Rev Neurol · June 2017
Astrocytic and oligodendroglial gliomas are intrinsic brain tumours characterized by infiltrative growth and resistance to classic cancer therapies, which renders them inevitably lethal. Glioblastoma, the most common type of glioma, also exhibits neoangiog ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleExpert Opin Biol Ther · April 2017
Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain - glioblastoma (GBM). Areas covered: ...
Full textLink to itemCite
Journal articleNeurosurgery · April 1, 2017
This workshop addressed challenges of clinical research in neurosurgery. Randomized controlled clinical trials (RCTs) have high internal validity, but often insufficiently generalize to real-world practice. Observational studies are inclusive but often lac ...
Full textLink to itemCite
Journal articleJ Neurooncol · March 2017
Pediatric surgical trials are rare and the impact of such trials on the institutions in which they are conducted is unknown. The purpose of this study was to analyze the clinical and financial impact of The Re-MATCH trial, a Phase I clinical trial requirin ...
Full textLink to itemCite
Journal articleExpert Opin Drug Saf · March 2017
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors w ...
Full textLink to itemCite
Journal articleOncoimmunology · 2017
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanolipos ...
Full textLink to itemCite
Journal articleExpert Rev Vaccines · January 2017
Glioblastoma is the most common primary brain tumor in adults and prognosis remains poor with a median survival of approximately 15-17 months. This review provides an overview of recent advances in the field of glioblastoma immunotherapy. Areas covered: Re ...
Full textLink to itemCite
Journal articleAdv Radiat Oncol · 2017
INTRODUCTION: Due to the neurocognitive side effects of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) is being used with increasing frequency. The use of SRS is expanding for patients with multiple (>4) brain metastases (BM). This s ...
Full textOpen AccessLink to itemCite
Journal articleFront Immunol · 2017
INTRODUCTION: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these fin ...
Full textLink to itemCite
Journal articleClin Cancer Res · November 1, 2016
Oncolytic viruses, proteasome inhibitors, and natural killer (NK)-cell immunotherapy have all been studied extensively as monotherapies but have never been evaluated in combination. Synergetic treatment of oncolytic virus-infected glioblastomas with a prot ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeurosurgery · August 2016
INTRODUCTION: Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is an effective immunotherapy for hematological cancers but requires a rethinking for clinical efficacy against solid tumors, where CARs have largely failed. Lymphodepl ...
Full textLink to itemCite
Journal articleTher Deliv · July 2016
The direct delivery of drugs and other agents into tissue (in contrast to systemic administration) has been used in clinical trials for brain cancer, neurodegenerative diseases and peripheral tumors. However, continuing evidence suggests that clinical effi ...
Full textLink to itemCite
Journal articleExpert Opin Emerg Drugs · June 2016
INTRODUCTION: Immunotherapy for brain cancer has evolved dramatically over the past decade, owed in part to our improved understanding of how the immune system interacts with tumors residing within the central nervous system (CNS). Glioblastoma (GBM), the ...
Full textLink to itemCite
Journal articleJ Alzheimers Dis · April 15, 2016
BACKGROUND: Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)-associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ). OBJECTIVE: We asked whether isoflurane and propofol have diffe ...
Full textOpen AccessLink to itemCite
Journal articleClin Cancer Res · February 1, 2016
PURPOSE: Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. ...
Full textLink to itemCite
Journal articleCancer Immunol Immunother · February 2016
Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator ...
Full textLink to itemCite
Journal articleNeuro Oncol · November 2015
Vaccination against cancer-associated antigens has long held the promise of inducting potent antitumor immunity, targeted cytotoxicity while sparing normal tissues, and long-lasting immunologic memory that can provide surveillance against tumor recurrence. ...
Full textLink to itemCite
Journal articleLancet Oncol · November 2015
Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed respons ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNat Rev Neurol · September 2015
Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment—maximal safe resection and combination of radiotherapy with temozolomide chemotherapy—the median overall survival ti ...
Full textLink to itemCite
Journal articleJ Neurooncol · July 2015
Glioblastoma multiforme (GBM) is an extremely malignant brain tumor for which current therapies do little to remedy. Despite aggressive treatment with surgery, radiation therapy, and chemotherapy, tumors inevitably recur as a direct consequence of the infi ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleOncoimmunology · June 2015
Conventional treatment for cancer routinely includes surgical resection and some combination of chemotherapy and radiation. These approaches are frequently accompanied by unintended and highly toxic collateral damage to healthy tissues, which are offset by ...
Full textLink to itemCite
Journal articleCancer Immunol Res · April 2015
Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimul ...
Full textLink to itemCite
Journal articleCancer Immunol Immunother · April 2015
Glioblastoma multiforme (GBM) is an aggressive malignancy associated with profound host immunosuppression mediated in part by FoxP3 expressing regulatory CD4+ T lymphocytes (Tregs) that down-regulate anti-tumor immunity. In order to assess whether FoxP3 wa ...
Full textLink to itemCite
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 ...
Full textOpen AccessLink to itemCite
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 ...
Full textLink to itemCite
Journal articleOncoimmunology · March 2015
In adoptive T cell transfer therapy (ACT), the antitumor efficacy of cytotoxic CD8+ T lymphocytes (CTLs) has been limited by tumor-induced immunosuppression. We have demonstrated that miR-23a blockade in tumor-specific CTLs conferred resilience to TGFβ-med ...
Full textLink to itemCite
Journal articleJ Vis Exp · February 16, 2015
Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo to express chimeric antigen receptors specific for glioma antigens (CAR T cells). The expansion and fu ...
Full textLink to itemCite
Journal articleExpert Opin Biol Ther · January 2015
INTRODUCTION: Patients with primary glioblastoma (GBM) have a dismal prognosis despite standard therapy, which can induce potentially deleterious side effects. Arming the immune system is an alternative therapeutic approach, as its cellular effectors and i ...
Full textLink to itemCite
Journal articleInt J Radiat Oncol Biol Phys · January 1, 2015
PURPOSE: To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. METHODS AND MATERIALS: Adult patients with 1 to 3 brain metastases less than 4 cm ...
Full textLink to itemCite
Journal articleSurg Neurol Int · 2015
Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery ...
Full textLink to itemCite
Journal articleJ Clin Invest · December 2014
CD8(+) cytotoxic T lymphocytes (CTLs) have potent antitumor activity and therefore are leading candidates for use in tumor immunotherapy. The application of CTLs for clinical use has been limited by the susceptibility of ex vivo-expanded CTLs to become dys ...
Full textLink to itemCite
Journal articleClin Cancer Res · November 15, 2014
Immunotherapy for cancer continues to gain both momentum and legitimacy as a rational mode of therapy and a vital treatment component in the emerging era of personalized medicine. Gliomas, and their most malignant form, glioblastoma, remain as a particular ...
Full textLink to itemCite
Journal articleCancer · November 1, 2014
Featured Publication
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 ...
Full textLink to itemCite
Journal articleNeuro Oncol · November 2014
Survival for patients with glioblastoma, the most common high-grade primary CNS tumor, remains poor despite multiple therapeutic interventions including intensifying cytotoxic therapy, targeting dysregulated cell signaling pathways, and blocking angiogenes ...
Full textLink to itemCite
Journal articleExpert Opin Pharmacother · October 2014
Featured Publication
INTRODUCTION: Malignant gliomas (MGs) represent the most common primary brain tumors in adults, the most deadly of which is grade IV glioblastoma. Patients with glioblastoma undergoing current standard-of-care therapy have a median survival of 12 - 15 mont ...
Full textLink to itemCite
Journal articleSemin Radiat Oncol · October 2014
In almost all patients, malignant glioma recurs following initial treatment with maximal safe resection, conformal radiotherapy, and temozolomide. This review describes the many options for treatment of recurrent malignant gliomas, including reoperation, a ...
Full textLink to itemCite
Journal articleNeuro Oncol · October 2014
Immunotherapeutic approaches to cancer have shown remarkable promise. A critical barrier to successfully executing such immune-mediated interventions is the selection of safe yet immunogenic targets. As patient deaths have occurred when tumor-associated an ...
Full textLink to itemCite
Journal articleJ Neurosurg · September 2014
Featured Publication
OBJECT: Robust methodology that allows objective, automated, and observer-independent measurements of brain tumor volume, especially after resection, is lacking. Thus, determination of tumor response and progression in neurooncology is unreliable. The obje ...
Full textLink to itemCite
Journal articleJ Neurosurg · August 2014
Featured Publication
OBJECT: On July 1, 2003, the Accreditation Council for Graduate Medical Education (ACGME) implemented duty-hour restrictions for resident physicians due to concerns for patient and resident safety. Though duty-hour restrictions have increased resident qual ...
Full textLink to itemCite
Journal articleSemin Oncol · August 2014
Conventional therapy for malignant glioma (MG) fails to specifically eliminate tumor cells, resulting in toxicity that limits therapeutic efficacy. In contrast, antibody-based immunotherapy uses the immune system to eliminate tumor cells with exquisite spe ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleClin Cancer Res · May 15, 2014
Featured Publication
PURPOSE: Despite aggressive conventional therapy, glioblastoma (GBM) remains uniformly lethal. Immunotherapy, in which the immune system is harnessed to specifically attack malignant cells, offers a treatment option with less toxicity. The expression of cy ...
Full textLink to itemCite
Journal articleClin Cancer Res · February 15, 2014
Featured Publication
PURPOSE: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to ...
Full textLink to itemCite
Journal articlePLoS One · 2014
Featured Publication
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 ...
Full textOpen AccessLink to itemCite
Journal articleImmunotherapy · 2014
Featured Publication
Glioblastoma multiforme (GBM) is the most common and aggressive glial cell-derived primary tumor. Current standard of care for patients with GBM includes maximal tumor resection plus adjuvant radiotherapy and temozolomide chemotherapy, increasing median ov ...
Full textLink to itemCite
Journal articleOncoimmunology · 2014
Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are c ...
Full textLink to itemCite
Journal articleOncoimmunology · 2014
First-line chemotherapy to combat primary malignant brain cancer is often accompanied by lymphopenic immunologic deficiency. Although counterintuitive, chemotherapy-induced lymphopenia can provide excellent host conditioning that may actually be leveraged ...
Full textLink to itemCite
Journal articleOncoimmunology · 2014
CAR therapy has shown promise in treating cancer, but at the cost of unexpected toxicity against normal tissues, not predicted by preclinical testing. We are working to generate more physiologically relevant models for preclinical CAR toxicity testing, and ...
Full textLink to itemCite
Journal articleJ Radiosurg SBRT · 2014
PURPOSE: For patients with primary CNS lymphoma who achieve complete response (CR) after induction methotrexate-based chemotherapy with rituximab, low-dose whole brain radiation therapy (LD-WBRT) appears effective and is well tolerated. For patients who re ...
Link to itemCite
Journal articleJ Clin Neurosci · January 2014
Featured Publication
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textCite
Journal articleCancer Immunol Immunother · November 2013
Adoptive cell transfer (ACT) using ex vivo-expanded anti-tumor T cells such as tumor-infiltrated lymphocytes or genetically engineered T cells potently eradicates established tumors. However, these two approaches possess obvious limitations. Therefore, we ...
Full textLink to itemCite
Journal articleJ Clin Neurosci · October 2013
We report a unique case of a dural-based inflammatory pseudotumor (IPT) arising in the left cavernous sinus of a patient with a history of juvenile Still's disease. The patient presented with hemi-facial paresthesias, dull, constant headaches, and transien ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleInt J Radiat Oncol Biol Phys · August 1, 2013
PURPOSE: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. METHODS AND MATERIALS: ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Neurosurg · August 2013
OBJECT: Rhabdoid glioblastoma (GB) is an exceedingly rare tumor in which some of the tumor cells possess rhabdoid features such as eccentric nuclei, abundant eosinophilic cytoplasm, and pseudopapillary formations. These tumors are exceptionally aggressive, ...
Full textLink to itemCite
Journal articleSurg Oncol Clin N Am · July 2013
In this article, the application of radiotherapy, alone and in combination with surgery and chemotherapy, in the treatment of metastases to the brain (the most common malignant brain lesion), primary malignant gliomas (the most common malignant primary bra ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Clin Invest · July 2013
BACKGROUND: Many cancers, including melanoma, exclusively express constitutive proteasomes (cPs) and are unable to express immunoproteasomes (iPs). In contrast, mature DCs used for immunotherapy exclusively express iPs. Since proteasomes generate peptides ...
Full textLink to itemCite
Journal articleNeurosurgery · June 2013
BACKGROUND: Despite advanced microsurgical techniques, more refined instrumentation, and expert team management, there is still a significant incidence of complications in vestibular schwannoma surgery. OBJECTIVE: To analyze complications from the microsur ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleExpert Rev Vaccines · June 2013
Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancer ...
Full textLink to itemCite
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 ...
Cite
Journal articleCancer Treat Rev · May 2013
We aim to summarize data from studies of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and brain metastasis and to describe novel methods being developed to circumvent the blood-brain b ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Bone Joint Surg Am · February 20, 2013
BACKGROUND: Surgical site infections increase the incidence of morbidity and mortality as well as health-care expenses. The cost of care increases threefold to fourfold as a consequence of surgical site infection after spinal surgery. The aim of the presen ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textOpen AccessLink to itemCite
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 ...
Full textLink to itemCite
Journal articleCurr Drug Discov Technol · December 2012
With an average life expectancy of 14 months, Glioblastoma multiforme (GBM), is the most aggressive primary brain tumor. Our growing understanding of the immune system and its role in oncogenesis has helped develop cancer vaccines as a promising treatment ...
Full textLink to itemCite
Journal articleClin Cancer Res · November 15, 2012
Indoleamine 2,3-dioxygenase (IDO) is an enzyme with known immunosuppressive and tolerogenic effects in cancer. Mounting evidence has associated IDO expression with the induction of regulatory T cells (Treg) and malignant progression. IDO inhibition may the ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textOpen AccessLink to itemCite
Journal articleJ Neurooncol · July 2012
To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of dasatinib, an inhibitor of the Src family kinase proteins, with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, among recurrent malignant glioma pat ...
Full textLink to itemCite
Journal articleTechnol Cancer Res Treat · June 2012
Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the b ...
Full textLink to itemCite
Journal articleJ Natl Compr Canc Netw · June 1, 2012
Despite contemporary surgery, image-guided radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) persists or relapses in nearly all patients, and tumors almost always recur locally. Management of recurrent GBM is variable, but approaches include be ...
Full textLink to itemCite
Journal articleNeurosurg Clin N Am · April 2012
Surgery remains one of the oldest and still most important forms of treatment for patients with glioma. The advantages of surgical resection for glioma must be balanced with the potential of operative morbidity to surrounding eloquent brain. To that end, a ...
Full textLink to itemCite
Journal articleInt J Radiat Oncol Biol Phys · April 1, 2012
PURPOSE: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. METHODS AND MATERIA ...
Full textLink to itemCite
Journal articleJ Neurooncol · March 2012
We evaluated the efficacy of carboplatin, irinotecan, and bevacizumab among bevacizumab-naïve, recurrent glioblastoma (GBM) patients in a phase 2, open-label, single arm trial. Forty eligible patients received carboplatin (area under the plasma curve [AUC] ...
Full textLink to itemCite
Journal articleInt J Radiat Oncol Biol Phys · January 1, 2012
PURPOSE: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: A total of 125 patients with newly diagnosed GBM were enrolled in ...
Full textLink to itemCite
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 ...
Full textOpen AccessLink to itemCite
Journal articleJ Neurooncol · January 2012
We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. A ...
Full textLink to itemCite
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 ...
Full textOpen AccessLink to itemCite
Journal articleNeurosurgery · January 2012
BACKGROUND: The Response Assessment in Neuro-Oncology (RANO) Working Group is an international, multidisciplinary effort to develop new standardized response criteria for clinical trials in brain tumors. The RANO group identified knowledge gaps relating to ...
Full textLink to itemCite
Journal articleCancer · December 1, 2011
BACKGROUND: The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, open-label, single-arm trial was evaluated. METHODS: Eligible patients received ca ...
Full textLink to itemCite
Journal articleJournal of Surgical Radiology · December 1, 2011
Introduction The Chiari I malformation is a rare pathological condition that is characterized by a downward herniation of the cerebellar tonsils and brainstem through the foramen magnum. The transformation from an asymptomatic to symptomatic Chiari I malfo ...
Cite
Journal articleCrit Rev Oncol Hematol · October 2011
Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant glioma (MG), with a median survival time of 12-15 months, despite current best treatment based on surgery, radiotherapy and systemic chemotherapy. Many potentially active therapeut ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleClin Cancer Res · July 15, 2011
Several investigators have now demonstrated the expression of genes unique to cytomegalovirus (CMV) in malignant gliomas. Many of these genes promote oncogenesis, alter tumor microenvironment, and serve as immunologic targets. Is the level of CMV infection ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Neurooncol · June 2011
We evaluated the efficacy of metronomic etoposide or temozolomide administered with bevacizumab among recurrent glioblastoma (GBM) patients who progressed on prior bevacizumab therapy in a phase 2, open-label, two-arm trial. Twenty-three patients received ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeuro Oncol · March 2011
To review the strengths and weaknesses of primary and auxiliary end points for clinical trials among patients with high-grade glioma (HGG). Recent advances in outcome for patients with newly diagnosed and recurrent HGG, coupled with the development of mult ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeuro Oncol · January 2011
With the recent approval by the FDA of an immunotherapy for prostate cancer and another positive immunotherapy trial in melanoma, immunotherapy may finally be coming of age. So what will it take for it to become part of the standard treatment for glioblast ...
Full textLink to itemCite
Journal articleJ Neurooncol · January 2011
The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) cath ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeurol Res · October 2010
OBJECTIVES: While convection enhanced delivery (CED) is an effective delivery method that bypasses the blood-brain barrier, its utility is limited by infusate leakage due to catheter misplacement. Therefore, it is critical to evaluate drug distribution dur ...
Full textLink to itemCite
Journal articleNeuro Oncol · August 2010
Convection-enhanced delivery (CED) of cintredekin besudotox (CB) was compared with Gliadel wafers (GW) in adult patients with glioblastoma multiforme (GBM) at first recurrence. Patients were randomized 2:1 to receive CB or GW. CB (0.5 microg/mL; total flow ...
Full textLink to itemCite
Journal articleJ Neurosurg · August 2010
OBJECT: Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet cl ...
Full textLink to itemCite
Journal articleJ Neurooncol · July 2010
Temporal paragangliomas are highly vascular tumors treated primarily by surgical resection. However, surgery to remove these tumors is associated with significant morbidity, including cranial nerve dysfunction. Interestingly, these tumors have been shown t ...
Full textLink to itemCite
Journal articleCurr Neurol Neurosci Rep · July 2010
Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful, glioma may be an ideal target for immune-based therapy. Recently, translational research ...
Full textLink to itemCite
Journal articleJ Neuroophthalmol · June 2010
Because of the success of stereotactic radiosurgery (SRS) in the treatment of cerebral arteriovenous malformations (AVMs), SRS is being applied to the treatment of carotid-cavernous dural arteriovenous fistulas (CCDAVFs) when these lesions are not accessib ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeuromethods · January 15, 2010
Convection-enhanced delivery (CED) is a method of direct intracerebral parenchymal infusion. It has been previously studied as a mechanism of drug delivery in glioma therapy, which is the focus of this review, and much work has gone into the utilization of ...
Full textCite
Journal articleJ Neurooncol · January 2010
We evaluated the anti-tumor activity and safety of erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent glioblastoma (GBM) ...
Full textLink to itemCite
Journal articleNeurosurg Clin N Am · January 2010
Glioblastoma multiforme is a malignant, relentless brain cancer with no known cure, and standard therapies leave significant room for the development of better, more effective treatments. Immunotherapy is a promising approach to the treatment of solid tumo ...
Full textLink to itemCite
Journal articleNeurosurg Clin N Am · January 2010
The role of regulatory T cells (Tregs) in mediating immune suppression of anti-tumor immune responses is increasingly appreciated in patients with malignancies-especially within the malignant glioma patient population. This article discuss the role and pro ...
Full textLink to itemCite
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 ...
Full textOpen AccessLink to itemCite
Journal articleJ Neurooncol · December 2009
This phase II trial evaluated efficacy and safety of temozolomide (TMZ) in combination with irinotecan (CPT-11) before radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Prior to radiotherapy, patients were treated with a maximum ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeurosurgery · September 2009
ObjectiveOur group has pioneered the use of gadoteridol-loaded liposomes (GDLs) in convection-enhanced delivery (CED) using real-time magnetic resonance imaging (MRI) to visualize the distribution of therapeutic agents in nonhuman primate and cani ...
Full textCite
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 ...
Full textLink to itemCite
Journal articleExpert Opin Biol Ther · August 2009
Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. EGFR variant III ( ...
Full textLink to itemCite
Journal articleInt J Cancer · August 1, 2009
The consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that immunoglobulin E (IgE) levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechan ...
Full textLink to itemCite
Journal articleCancer · July 1, 2009
BACKGROUND: The current study was a phase 1 clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG). The trial was designed to determine the maximum tolerated dose (MTD) and toxicity of irinotecan (CPT-11) when adminis ...
Full textLink to itemCite
Journal articleNeurotherapeutics · July 2009
The immunologic treatment of cancer has long been heralded as a targeted molecular therapeutic with the promise of eradicating tumor cells with minimal damage to surrounding normal tissues. However, a demonstrative example of the efficacy of immunotherapy ...
Full textLink to itemCite
Journal articleAm J Clin Oncol · June 2009
OBJECTIVES: Paragangliomas are rare neuroendocrine neoplasms of the head and neck. Treatment strategies include resection, definitive external beam radiation therapy (EBRT), stereotactic radiosurgery (SRS), or observation alone. Due to their rarity and ind ...
Full textLink to itemCite
Journal articleJ Neurochem · May 2009
Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P incre ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleInt J Radiat Oncol Biol Phys · April 1, 2009
PURPOSE: To describe our experience and clinical strategy for stereotactic body radiotherapy (SBRT) of spinal lesions. METHODS AND MATERIALS: Thirty-two patients with 33 spinal lesions underwent computed tomography-based simulation while free breathing. Gr ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Neurosurg · November 2008
OBJECT: The authors have shown that convection-enhanced delivery (CED) of gadoteridol-loaded liposomes (GDLs) into different regions of normal monkey brain results in predictable, widespread distribution of this tracking agent as detected by real-time MR i ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleClin Cancer Res · September 15, 2008
PURPOSE: Activation of signal transducers and activators of transcription 3 (STAT3) has been identified as a central mediator of melanoma growth and metastasis. We hypothesized that WP1066, a novel STAT3 blockade agent, has marked antitumor activity, even ...
Full textLink to itemCite
Journal articleJ Neurooncol · August 2008
OBJECTIVE AND IMPORTANCE: We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleFuture Oncol · June 2008
Despite maximal therapy, malignant gliomas have a very poor prognosis. Patients with glioma express significant immune defects, including CD4 lymphopenia, increased fractions of regulatory T cells in peripheral blood and shifts in cytokine profiles from Th ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleHum Gene Ther · May 2008
It has been observed that the efficient transfection of T cells by RNA electroporation requires prior activation of T cells with mitogens or by anti-CD3 antibody stimulation. We hypothesized that this requirement for T cell activation could be leveraged to ...
Full textLink to itemCite
Journal articleNeurosurg Rev · April 2008
The standard treatment paradigm of surgery, radiation, and chemotherapy for malignant gliomas has only a modest effect on survival. It is well emphasized in the literature that despite aggressive multimodal therapy, most patients survive approximately 1 ye ...
Full textLink to itemCite
Journal articleImmunol Rev · April 2008
Despite aggressive multi-modality therapy including surgery, radiation, and chemotherapy, the prognosis for patients with malignant primary brain tumors remains very poor. Moreover, the non-specific nature of conventional therapy for brain tumors often res ...
Full textLink to itemCite
Journal articleNeuro Oncol · February 2008
Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated ...
Full textLink to itemCite
Journal articleJ Neurosurg · February 2008
Cholesterol granulomas (CGs) are benign lesions resulting from an inflammatory reaction to cholesterol and hemosiderin. These masses most often arise within the temporal bone or nasal sinuses; intracerebral CGs are extremely rare. In this report the author ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeurosurgery · November 2007
OBJECTIVE: Cintredekin besudotox (CB), a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13R alpha2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB a ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Neurooncol · May 2007
PURPOSE: Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 s ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Clin Oncol · March 1, 2007
PURPOSE: Glioblastoma multiforme (GBM) is a devastating brain tumor with a median survival of 6 months after recurrence. Cintredekin besudotox (CB) is a recombinant protein consisting of interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin ( ...
Full textLink to itemCite
Journal articleGynecol Oncol · March 2007
PURPOSE: To report our recent experience managing four patients with brain metastases of gestational trophoblastic neoplasia (GTN), coordinating systemic chemotherapy with early neurosurgical intervention or stereotactic radiosurgery and intensive supporti ...
Full textLink to itemCite
Journal articleAJR Am J Roentgenol · March 2007
OBJECTIVE: Convection-enhanced delivery is a promising approach to intracerebral drug delivery in which a fluid pressure gradient is used to infuse therapeutic macromolecules through an indwelling catheter into the interstitial spaces of the brain. Our pur ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Neuroimmunol · January 2007
For the study of malignant glioma, we have previously characterized a highly tumorigenic murine astrocytoma, SMA-560, which arose spontaneously in an inbred, immunocompetent VM/Dk mouse. Using this cell line as a model of murine glioma, we performed DNA mi ...
Full textLink to itemCite
Journal articleClin Cancer Res · December 15, 2006
PURPOSE: Analyses of T-cell mRNA expression profiles in glioblastoma multiforme has not been previously reported but may help to define and characterize the immunosuppressed phenotype in patients with this type of cancer. EXPERIMENTAL DESIGN: We did microa ...
Full textLink to itemCite
Journal articleNeurol Med Chir (Tokyo) · October 2006
The topoisomerase I inhibitor, 9-nitro-camptothecin (9NC), is highly tumoricidal against glioblastoma multiforme (GBM) in vitro. However, systemic administration of 9NC has not shown the expected efficacy in clinical trials. This failure may be due to the ...
Full textLink to itemCite
Journal articleRadiology · September 2006
PURPOSE: To prospectively evaluate the effect of preoperative functional magnetic resonance (MR) imaging localization of language and motor areas on therapeutic decision making in patients with potentially resectable brain tumors. MATERIALS AND METHODS: Th ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Link to itemCite
Journal articleNeurosurg Focus · April 15, 2006
Convection-enhanced delivery (CED) is the continuous injection under positive pressure of a fluid containing a therapeutic agent. This technique was proposed and introduced by researchers from the US National Institutes of Health (NIH) by the early 1990s t ...
Full textLink to itemCite
Journal articleNeurosurg Focus · April 15, 2006
OBJECT: Convection-enhanced delivery (CED) is an increasingly used novel local/regional delivery method targeted directly to tissue. It relies on a continuous pressure gradient for distribution of therapeutic agents into the interstitial space, with admini ...
Link to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleClin Cancer Res · February 15, 2006
PURPOSE: The toxicity and antitumor activity of regional intrathecal delivery of an oncolytic recombinant poliovirus, PVS-RIPO, was evaluated in rodent models of glioblastoma multiforme neoplastic meningitis. EXPERIMENTAL DESIGN: To evaluate for toxicity, ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJ Clin Oncol · December 20, 2005
PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiform ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeurosurgery · March 2005
OBJECTIVE: Meningiomas arising from the petroclival region remain a challenging surgical problem. Because of the substantial risk of neurological morbidity, uniformly pursuing a gross total resection (GTR) to minimize tumor recurrence rates may not be just ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleClin Cancer Res · July 15, 2004
PURPOSE: Spread to the central nervous system (CNS) and the leptomeninges is a frequent complication of systemic cancers that is associated with serious morbidity and high mortality. We have evaluated a novel therapeutic approach against CNS complications ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeurosurgery · April 2004
OBJECTIVE: To establish the long-term safety, efficacy, and durability of microvascular decompression (MVD) for the treatment of glossopharyngeal neuralgia, this study presents the immediate (<6 mo) postoperative and long-term results of a large series of ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleJournal of ethnopharmacology · January 2004
The SRB assay was used to test cytotoxicity against three human cancer cell lines and one normal cell line of 11 Thai medicinal plant species used by traditional doctors in treating cancer patients. The extraction procedures used were similar to those prac ...
Cite
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 ...
Full textLink to itemCite
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 ...
Link to itemCite
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 ...
Full textLink to itemCite
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 ...
Link to itemCite
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 ...
Full textLink to itemCite
Journal articleCancer J · 2003
Despite remarkable advancements in imaging modalities and treatment options available to patients diagnosed with malignant brain tumors, the prognosis for those with high-grade lesions remains poor. The imprecise mechanisms of currently available treatment ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleNeuroimaging Clin N Am · November 2002
As an immunization platform for brain tumors, dendritic cells supply an impressive host of advantages. On the simplest level, they provide the safety and tumor-specificity so wanted by current therapeutic options. Yet, in addition, as the fundamental antig ...
Full textLink to itemCite
Journal articleClin Cancer Res · November 2002
Featured Publication
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 ...
Link to itemCite
Journal articleNeuroimaging Clin N Am · November 2002
The grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. Viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vecto ...
Full textLink to itemCite
Journal articleAJNR Am J Neuroradiol · October 2002
Featured Publication
Three cases of intracanalicular meningioma mimicking vestibular schwannoma are presented. In each case, a contrast-enhancing mass filling the internal auditory canal was identified on MR images and was originally diagnosed as a vestibular schwannoma. Altho ...
Link to itemCite
Journal articleCancer Res · June 15, 2002
Featured Publication
The gene most commonly altered in human glioblastomas is the epidermalgrowth factor receptor (EGFR). We profiled transcripts induced by mutantEGFR to better understand its role in tumor progression. The pattern found suggested enhanced tumor invasion. The ...
Link to itemCite
Journal articleJ Clin Oncol · May 1, 2002
Featured Publication
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 ...
Full textLink to itemCite
Journal articleJ Clin Oncol · March 1, 2002
Featured Publication
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 ...
Full textLink to itemCite
Journal articleCancer Immunol Immunother · February 2002
Featured Publication
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, ...
Full textLink to itemCite
Journal articleNeurosurgery · January 2002
Featured Publication
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 ...
Full textLink to itemCite
Journal articleNeuro Oncol · October 2001
Both Gliadel wafers [1,3-bis(2-chloroethyl)-1-nitrosourea] and temozolomide (TEMO) have been shown in independent studies to prolong survival of patients with recurrent malignant glioma following surgery and radiotherapy. On the basis of preclinical eviden ...
Full textLink to itemCite
Journal articlePhytomedicine · May 2001
Psoriasis is a hyperproliferative skin disorder estimated to be present in 1-3% of most populations. Conventional therapy using corticosteroids, Vitamin D analogs and cytotoxic agents eg psoralens is associated with low success rate and many side effects. ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Link to itemCite
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 ...
Full textCite
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 ...
Full textLink to itemCite
Journal articlePhytother Res · February 2000
A number of plant species used in traditional medicine for the relief of pain have been selected from the medicinal and scientific literature of China, South America, Asia and West Africa. Extracts were prepared and tested in three in vitro receptor radiol ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Link to itemCite
Journal articleClin Cancer Res · May 1999
Featured Publication
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 ...
Link to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleAIDS · October 22, 1998
OBJECTIVES: To describe the methods and results of a standardized system for clinical endpoint determination for defining and reviewing endpoints in clinical trials for HIV-infected individuals. DESIGN: A system was developed utilizing standard definitions ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleAIDS · February 12, 1998
OBJECTIVE: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV disease. DESIGN: Double-blind, placebo-controlled, randomized clinical trial in primary care clinics ...
Full textLink to itemCite
Journal articleJ Neurosurg · January 1998
Featured Publication
UNLABELLED: Brain metastases are a common and devastating complication in patients with malignant melanoma. Therapeutic options for these patients are limited, and the prognosis is usually poor. OBJECT: A retrospective review of 6953 patients with melanoma ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
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 ...
Full textLink to itemCite
Journal articleAIDS Res Hum Retroviruses · March 1, 1997
This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight a ...
Full textLink to itemCite
Journal articleAm J Respir Crit Care Med · November 1996
Infection with human immunodeficiency virus (HIV) has been associated with increased rates of single- and multidrug-resistant (MDR) tuberculosis in the New York City area. In order to examine the relationship of HIV infection to drug-resistant tuberculosis ...
Full textLink to itemCite
Journal articleProc Natl Acad Sci U S A · September 17, 1996
Featured Publication
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 ...
Full textLink to itemCite
Journal articleJ Neurosurg · May 1996
Complete excision of a cerebral arteriovenous malformation (AVM) should eliminate the future risk of an associated intracranial hemorrhage. Because total removal of an AVM may be difficult to assess at the time of surgery, postoperative angiography has bec ...
Full textLink to itemCite
Journal articleNeurosurgery · November 1995
A 47-year-old woman with left ear pain and hearing loss was diagnosed with a glomus jugulare tumor for which she received radiation therapy as the primary treatment. Over a period of 20 years, she developed temporal bone necrosis, brain stem calcifications ...
Full textLink to itemCite
Journal articleSpine (Phila Pa 1976) · October 1, 1995
STUDY DESIGN: One-hundred-fourteen patients with metastatic melanoma of the spine were retrospectively reviewed. OBJECTIVE: The goal was to define the demographics, risk factors, and prognosis for this population. SUMMARY OF BACKGROUND DATA: The incidence ...
Full textLink to itemCite
Journal articleJ Neurosurg · January 1995
This review was undertaken to determine the efficacy of using dorsal root entry zone (DREZ) lesions to treat intractable pain caused by trauma to the conus medullaris and cauda equina. Traumatic lesions of this area are unique in that both the spinal cord ...
Full textLink to itemCite
Journal articleAnn Intern Med · August 1, 1994
OBJECTIVE: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodefici ...
Full textLink to itemCite
Journal articleSurg Neurol · August 1993
Current cerebrospinal fluid shunts use complex differential pressure values to regulate drainage. Such systems are prone to overdrainage and obstruction, and thus have an unpredictable effect on intracranial pressure (ICP). The gravitational shunt (GS) int ...
Full textLink to itemCite
Journal articleNeurosurgery · October 1992
A 41-year-old white man with facial pain and diplopia was found to have an invasive lesion of the clivus. The final pathological diagnosis was eosinophilic granuloma. The patient's symptoms resolved completely after transsphenoidal resection of the lesion. ...
Full textLink to itemCite
Journal articleJ Neurosurg · September 1992
One patient with a pontine infarct due to a fusiform basilar artery aneurysm and one with an arteriovenous malformation within the tectum of the mesencephalon developed intractable facial pain. This pain was relieved in both patients by radiofrequency lesi ...
Full textLink to itemCite
Journal articleAm Fam Physician · June 1992
Head injuries are the most common cause of disability and death in children. Identification of children who require specialized management following a head injury will reduce the associated morbidity and mortality. Thus, it is important to differentiate th ...
Link to itemCite