Journal ArticleActa Neuropathol Commun · April 22, 2024
Glioblastoma (GBM) remains an untreatable malignant tumor with poor patient outcomes, characterized by palisading necrosis and microvascular proliferation. While single-cell technology made it possible to characterize different lineage of glioma cells into ...
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Journal ArticleCancers (Basel) · September 18, 2023
Brain tumor-initiating cells (BTICs) and tumor cell plasticity promote glioblastoma (GBM) progression. Here, we demonstrate that clemastine, an over-the-counter drug for treating hay fever and allergy symptoms, effectively attenuated the stemness and suppr ...
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Journal ArticleNeuro Oncol · September 5, 2023
BACKGROUND: Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers uses telomerase-independent mechanisms termed alternative lengthening ...
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Journal ArticleLancet Child Adolesc Health · July 2023
BACKGROUND: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric ...
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Journal ArticleClin Transl Oncol · March 2023
BACKGROUND: Medulloblastoma is the most common pediatric malignant brain tumor, consisting of four molecular subgroups (WNT, SHH, Group 3, Group 4) and 12 subtypes. Expression of the cell surface poliovirus receptor (PVR), CD155, is necessary for entry of ...
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Journal ArticleSci Transl Med · February 8, 2023
D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized tha ...
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Journal ArticleNeuro Oncol · November 2, 2022
BACKGROUND: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecular ...
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Journal ArticleNature · September 2022
Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rho ...
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Journal ArticleNeurooncol Pract · August 2022
BACKGROUND: The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic ...
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Journal ArticleHematol Oncol Clin North Am · February 2022
In 2016, the World Health Organization Classification of CNS Tumors introduced molecular abnormalities that refined tumor diagnoses. Around this time, the introduction of large scale genetic mutational analyses quickly advanced our knowledge of recurrent a ...
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Journal ArticleClin Cancer Res · December 15, 2021
PURPOSE: To investigate the therapeutic role of a novel telomere-directed inhibitor, 6-thio-2'-deoxyguanosine (THIO) in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: A panel of human and mouse glioma cell lines was used to test therapeutic effica ...
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ConferenceNeuro-Oncology · November 12, 2021
AbstractINTRODUCTIONVaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vac ...
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Journal ArticleActa Neuropathol · November 2021
Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) ...
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Journal ArticleNeuro Oncol · August 2, 2021
BACKGROUND: Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification. METHODS: Five independent non-overlapping cohorts of PF-EPN-A were analy ...
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Journal ArticleNat Commun · March 19, 2021
Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among ...
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Journal ArticleActa Neuropathol Commun · April 22, 2024
Glioblastoma (GBM) remains an untreatable malignant tumor with poor patient outcomes, characterized by palisading necrosis and microvascular proliferation. While single-cell technology made it possible to characterize different lineage of glioma cells into ...
Full textOpen AccessLink to itemCite
Journal ArticleCancers (Basel) · September 18, 2023
Brain tumor-initiating cells (BTICs) and tumor cell plasticity promote glioblastoma (GBM) progression. Here, we demonstrate that clemastine, an over-the-counter drug for treating hay fever and allergy symptoms, effectively attenuated the stemness and suppr ...
Full textLink to itemCite
Journal ArticleNeuro Oncol · September 5, 2023
BACKGROUND: Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers uses telomerase-independent mechanisms termed alternative lengthening ...
Full textLink to itemCite
Journal ArticleLancet Child Adolesc Health · July 2023
BACKGROUND: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric ...
Full textLink to itemCite
Journal ArticleClin Transl Oncol · March 2023
BACKGROUND: Medulloblastoma is the most common pediatric malignant brain tumor, consisting of four molecular subgroups (WNT, SHH, Group 3, Group 4) and 12 subtypes. Expression of the cell surface poliovirus receptor (PVR), CD155, is necessary for entry of ...
Full textLink to itemCite
Journal ArticleSci Transl Med · February 8, 2023
D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized tha ...
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Journal ArticleNeuro Oncol · November 2, 2022
BACKGROUND: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecular ...
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Journal ArticleNature · September 2022
Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rho ...
Full textLink to itemCite
Journal ArticleNeurooncol Pract · August 2022
BACKGROUND: The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic ...
Full textLink to itemCite
Journal ArticleHematol Oncol Clin North Am · February 2022
In 2016, the World Health Organization Classification of CNS Tumors introduced molecular abnormalities that refined tumor diagnoses. Around this time, the introduction of large scale genetic mutational analyses quickly advanced our knowledge of recurrent a ...
Full textLink to itemCite
Journal ArticleClin Cancer Res · December 15, 2021
PURPOSE: To investigate the therapeutic role of a novel telomere-directed inhibitor, 6-thio-2'-deoxyguanosine (THIO) in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: A panel of human and mouse glioma cell lines was used to test therapeutic effica ...
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ConferenceNeuro-Oncology · November 12, 2021
AbstractINTRODUCTIONVaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vac ...
Full textOpen AccessLink to itemCite
Journal ArticleActa Neuropathol · November 2021
Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) ...
Full textLink to itemCite
Journal ArticleNeuro Oncol · August 2, 2021
BACKGROUND: Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification. METHODS: Five independent non-overlapping cohorts of PF-EPN-A were analy ...
Full textLink to itemCite
Journal ArticleNat Commun · March 19, 2021
Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among ...
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Journal ArticleJ Clin Oncol · March 1, 2021
PURPOSE: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. METHODS: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00 ...
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Journal ArticleNat Commun · January 13, 2021
Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunother ...
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Journal ArticleCell Rep Med · June 23, 2020
Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this ...
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Journal ArticleNat Commun · June 17, 2020
Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on ...
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Journal ArticleClin Cancer Res · March 1, 2020
PURPOSE: Although pituitary adenoma is classified as benign, Cushing disease is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for Cushing disease remains elusive due to high rates of trea ...
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Journal ArticleActa Neuropathol · February 2020
Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly occurring in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. SMARCB1-mutant tumors in adolescents and adults are rare and may show uncommo ...
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Journal ArticleSci Adv · November 2019
In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurali ...
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Journal ArticleJ Neuropathol Exp Neurol · September 1, 2019
Infratentorial glioneuronal neoplasms are overall quite rare and are more commonly low-grade with surgical excision usually being curative. Multiple distinct histologic entities have been described including rosette-forming glioneuronal tumor, papillary gl ...
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Journal ArticleAm J Forensic Med Pathol · September 2019
Primary central nervous system tumors are an extremely rare cause of sudden, unexpected death in children as most patients develop symptoms because of increased intracranial pressure and seek medical attention. Rarely, a forensic pathologist may encounter ...
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Journal ArticleCancer Res · July 1, 2019
Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic ...
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Journal ArticleNeuro Oncol · March 18, 2019
BACKGROUND: Mutations in telomerase reverse transcriptase promoter (TERTp) and isocitrate dehydrogenase 1 and 2 (IDH) offer objective markers to assist in classifying diffuse gliomas into genetic subgroups. However, traditional mutation detection technique ...
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Journal ArticleActa Neuropathol Commun · March 15, 2019
Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-define ...
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Journal ArticleNat Commun · March 4, 2019
Diffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor, with approximately 25% of DIPGs harboring activating ACVR1 mutations that commonly co-associate with H3.1K27M mutations. Here we show that in vitro expression of ACVR1 R206H wit ...
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Journal ArticleAm J Clin Pathol · February 4, 2019
OBJECTIVES: The list of tumors involving the pituitary gland has been expanded to include a variety of neuronal and paraneuronal tumors in the 2017 World Health Organization tumor classification of endocrine organs. All the entities included in this catego ...
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Journal ArticleJ Neuropathol Exp Neurol · February 1, 2019
Rare pilocytic astrocytomas (PA) have been described to arise in the ventricles of children. They are even less common in this location for the adult population. We present the case of a 44-year old man presenting with vision and mental status changes. Bra ...
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Journal ArticleJ Neuropathol Exp Neurol · January 1, 2019
Glioma therapeutic resistance to alkylating chemotherapy is mediated via O6-methylguanine-DNA methyltransferase (MGMT). We hypothesized that a CD45/HAM56/MGMT double-stained cocktail would improve MGMT discrimination in tumor cells versus inflammatory and ...
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Journal ArticleFront Oncol · 2019
Myxopapillary ependymomas are a slow-growing, grade I type glial tumor in the lumbosacral region. More rarely, they can present as extradural, subcutaneous sacrococcygeal, or perisacral masses, and it is under these circumstances that they are more likely ...
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Journal ArticleSemin Oncol Nurs · December 2018
OBJECTIVE: To explain several biomarkers used in primary adult brain tumor diagnosis and the methodologies for their application. DATA SOURCES: Peer-reviewed literature. CONCLUSION: In the past few years, several biomarkers have been touted as providing re ...
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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 ...
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Journal ArticleNeuropathology · October 2018
Central neurocytoma is a rare neuronal tumor that typically occurs in young adults. Infrequently, these tumors exhibit advanced neuronal maturation and glial differentiation, giving rise to a histologically diverse tumor, in contrast to a typical central n ...
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Journal ArticleBrain Tumor Pathol · October 2018
Ollier disease (OD) and Maffucci syndrome are rare conditions due to a post-zygotic somatic mutation that results in mosaicism. In addition to enchondromas and hemangiomas, some of these patients also develop other unrelated tumors, such as gliomas, that h ...
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Journal ArticleJ Neuropathol Exp Neurol · September 1, 2018
Diagnosis and classification of poorly differentiated tumors with primitive features of the central nervous system heavily relies on molecular and genetic findings of the tumors. Although RB1 gene mutation underlies the development of retinoblastoma and ma ...
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Journal ArticleClin Cancer Res · August 1, 2018
Purpose: Conventional therapy for malignant glioma fails to specifically target tumor cells. In contrast, substantial evidence indicates that if appropriately redirected, T cells can precisely eradicate tumors. Here we report the rational development of a ...
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Journal ArticleJ Neuropathol Exp Neurol · August 1, 2018
Poliovirus oncolytic immunotherapy is a putatively novel approach to treat pediatric brain tumors. This work sought to determine expression of the poliovirus receptor (PVR), CD155, in low-grade and malignant pediatric brain tumors and its ability to infect ...
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Journal ArticleActa Neuropathol · August 2018
Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidanc ...
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Journal ArticleN Engl J Med · July 12, 2018
BACKGROUND: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating ...
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Journal ArticleNat Commun · May 25, 2018
The majority of glioblastomas can be classified into molecular subgroups based on mutations in the TERT promoter (TERTp) and isocitrate dehydrogenase 1 or 2 (IDH). These molecular subgroups utilize distinct genetic mechanisms of telomere maintenance, eithe ...
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Journal ArticleImmunity · April 17, 2018
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-Îģ dominant, inflammatory, lymphocyt ...
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Journal ArticleCancer Cell · April 9, 2018
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and c ...
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Journal ArticleCancer Cell · April 9, 2018
We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1, ...
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Journal ArticleCancer Cell · April 9, 2018
Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of pro ...
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Journal ArticleCancer Cell · April 9, 2018
We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We f ...
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Journal ArticleCell · April 5, 2018
The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we pr ...
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Journal ArticleCell · April 5, 2018
We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chr ...
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Journal ArticleCell · April 5, 2018
We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including ...
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Journal ArticleCell · April 5, 2018
The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 892 ...
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Journal ArticleCell · April 5, 2018
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tu ...
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Journal ArticleCell · April 5, 2018
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one ...
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Journal ArticleCell · April 5, 2018
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features represe ...
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Journal ArticleCell · April 5, 2018
Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analy ...
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Journal ArticleCell Rep · April 3, 2018
Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, includ ...
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Journal ArticleCell Rep · April 3, 2018
Long noncoding RNAs (lncRNAs) are commonly dysregulated in tumors, but only a handful are known to play pathophysiological roles in cancer. We inferred lncRNAs that dysregulate cancer pathways, oncogenes, and tumor suppressors (cancer genes) by modeling th ...
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Journal ArticleCell Rep · April 3, 2018
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation ra ...
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Journal ArticleCell Rep · April 3, 2018
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs) based on H&E images from 13 TCGA t ...
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Journal ArticleCell Rep · April 3, 2018
Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabo ...
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Journal ArticleCell Rep · April 3, 2018
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recu ...
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Journal ArticleCell Rep · April 3, 2018
Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atla ...
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Journal ArticleCell Rep · April 3, 2018
Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these "hidden responders" may reveal responsive molecular states. We describe and evaluate a machine-le ...
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Journal ArticleCell Rep · April 3, 2018
Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome ...
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Journal ArticleCell Rep · April 3, 2018
For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creat ...
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Journal ArticleCell Rep · April 3, 2018
DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heter ...
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Journal ArticleCell Syst · March 28, 2018
Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational ...
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Journal ArticleCell Syst · March 28, 2018
The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Can ...
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Journal ArticleCancer Res · January 1, 2018
Median survival for glioblastoma (GBM) remains <15 months. Human cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recen ...
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Journal ArticleCancer Res · January 1, 2018
Hotspot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of Îą-ketoglutarate (ÎąKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malign ...
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Journal ArticleClin Neuropathol · 2018
INTRODUCTION: Edema is a significant cause of neuromorbidity in children and adults with brain tumors. Agents used to control this effect, such as corticosteroids, have their own associated morbidities. Sulfonylurea receptor 1 (SUR1) is a transmembrane pro ...
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Journal ArticleArch Pathol Lab Med · December 2017
CONTEXT: - The oncolytic polio-rhinovirus recombinant (PVSRIPO) has demonstrated promise in currently ongoing phase I/II clinical trials against recurrent glioblastoma and was granted breakthrough therapy designation by the Food and Drug Administration/Cen ...
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Journal ArticleCancer Res · November 15, 2017
Inactivating mutations in the transcriptional repression factor Capicua (CIC) occur in approximately 50% of human oligodendrogliomas, but mechanistic links to pathogenesis are unclear. To address this question, we generated Cic-deficient mice and human oli ...
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Journal ArticleMol Cancer Res · September 2017
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epig ...
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Journal ArticleEpilepsy Behav · August 2017
OBJECTIVES: To describe the characteristics of epilepsy in patients with Neurofibromatosis type 1 (NF1). METHODS: Analysis of a cohort of consecutive NF1 patients seen in our NF1 clinic during a three-year period. RESULTS: Of the 184 NF1 patients seen duri ...
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Journal ArticleNature · July 19, 2017
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to id ...
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Journal ArticleMol Cancer Res · May 2017
IDH1 mutations occur in the majority of low-grade gliomas and lead to the production of the oncometabolite, D-2-hydroxyglutarate (D-2HG). To understand the effects of tumor-associated mutant IDH1 (IDH1-R132H) on both the neural stem cell (NSC) population a ...
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Journal ArticleClin Cancer Res · April 15, 2017
Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can e ...
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Journal ArticleJ Neuropathol Exp Neurol · March 1, 2017
The aim of this study was to characterize the type and degree of discrepancies between non-expert and expert diagnoses of CNS tumors to identify the value of consultations in surgical neuropathology. Neuropathology experts from 5 National Comprehensive Can ...
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Journal ArticleNeuro Oncol · January 2017
BACKGROUND: Astroblastomas (ABs) are rare glial tumors showing overlapping features with astrocytomas, ependymomas, and sometimes other glial neoplasms, and may be challenging to diagnose. METHODS: We examined clinical, histopathological, and molecular fea ...
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Journal ArticleJ Exp Med · January 2017
Glioblastoma is the most lethal brain tumor and harbors glioma stem cells (GSCs) with potent tumorigenic capacity. The function of GSCs in tumor propagation is maintained by several core transcriptional regulators including c-Myc. c-Myc protein is tightly ...
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Journal ArticleAcad Pathol · 2017
This retrospective observational study on faculty development analyzes the Duke University Pathology Department's 18-year experience with a structured mentoring program involving 51 junior faculty members. The majority had MD degrees only (55%). The percen ...
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Journal ArticleJ Immunol · December 15, 2016
The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cro ...
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Journal ArticleJ Clin Oncol · July 20, 2016
PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma a ...
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Journal ArticleAm J Med Genet A · June 2016
Although optic pathway gliomas are the most common brain tumors associated with neurofibromatosis type 1 (NF1), extra-optic gliomas occur and may behave more aggressively with outcomes that differ by age. A retrospective case-control study was designed to ...
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Journal ArticleCancer Res · April 15, 2016
Many cancers feature cellular hierarchies that are driven by tumor-initiating cancer stem cells (CSC) and rely on complex interactions with the tumor microenvironment. Standard cell culture conditions fail to recapitulate the original tumor architecture or ...
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Journal ArticleInvest New Drugs · April 2016
D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2 ...
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Journal ArticleLancet Oncol · April 2016
BACKGROUND: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensi ...
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Book · March 31, 2016
The management of patients with a glioma is challenging and best achieved by a team approach encompassing a combination of chemotherapy, radiotherapy, immunotherapy, and surgical excision in a specialist Cancer Center - the balance of treatment depending o ...
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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. ...
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Journal ArticleCancer Cell · January 11, 2016
The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit t ...
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Journal ArticleCase Rep Oncol · 2016
INTRODUCTION: Pilomyxoid astrocytoma (PMA) is a rare and more aggressive variant of pilocytic astrocytoma, which usually affects young children and is most often located in the hypothalamic/chiasmatic region. The association of PMA with underlying genetic ...
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Journal ArticlePediatr Blood Cancer · October 2015
We present three cases of genetically confirmed Gorlin syndrome with desmoplastic medulloblastoma (DMB) in whom tumor recurred despite standard therapy. One patient was found to have a novel germline missense PTCH1 mutation. Molecular analysis of recurrent ...
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Journal ArticleN Engl J Med · June 25, 2015
BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic cl ...
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Journal ArticleJ Neurochem · June 2015
The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characte ...
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Journal ArticleAm J Clin Pathol · June 2015
OBJECTIVES: Second opinions on neuropathology cases are sought for a variety of reasons. We investigated the rationales for seeking expert neuropathologic review. METHODS: A retrospective review was done of the correspondence accompanying neuropathology ca ...
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Journal ArticleJ Neurooncol · April 2015
Histologic grading methods dependent upon H&E staining review have not been shown to reliably predict survival in children with intracranial ependymomas due to the subjectivity of the analytical methods. We hypothesized that the immunohistochemical detecti ...
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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 ...
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Journal ArticleNature · March 19, 2015
After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vacci ...
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Journal ArticleNat Cell Biol · February 2015
Tumour-associated macrophages (TAMs) are enriched in glioblastoma multiformes (GBMs) that contain glioma stem cells (GSCs) at the apex of their cellular hierarchy. The correlation between TAM density and glioma grade suggests a supportive role for TAMs in ...
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Journal ArticleCase Rep Oncol · 2015
Ependymomas, tumors of the ependymal cells, are very rare and usually present in the pediatric population. Furthermore, there are even rarer variants of ependymomas that can include cellular, papillary, clear cell, and tanycytic subtypes. We present a case ...
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Journal ArticleJ Clin Invest · October 2014
Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GB ...
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ConferenceCancer Research · October 1, 2014
AbstractDespite decades worth of research, glioblastoma remains one of the most lethal cancers. The identification of IDH1 as a major cancer gene in glioblastoma provides a great opportunity for improving ou ...
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Journal ArticleJ Clin Invest · September 2014
Aberrant activation of EGFR in human cancers promotes tumorigenesis through stimulation of AKT signaling. Here, we determined that the discoidina neuropilin-like membrane protein DCBLD2 is upregulated in clinical specimens of glioblastomas and head and nec ...
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Journal ArticleJ Neurooncol · August 2014
Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the n ...
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Journal ArticleStem Cells · August 2014
Glioblastomas are highly lethal brain tumors containing tumor-propagating glioma stem cells (GSCs). The molecular mechanisms underlying the maintenance of the GSC phenotype are not fully defined. Here we demonstrate that the zinc finger and X-linked transc ...
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Journal ArticleNat Genet · July 2014
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ...
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Journal ArticleNeuro Oncol · July 2014
Malignant cells must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome ...
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Journal ArticleNeuro Oncol · July 2014
NELL2 expression has been shown to identify patients with posterior fossa ependymomas (PFEp) that exhibit prolonged survivals. We analyzed expression NELL2; KI-67; Tenascin C; CD34; VEGF; and CA IX as well as vascular density against post-operative surviva ...
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Journal ArticleOncotarget · March 30, 2014
Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or o ...
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Journal ArticleOncotarget · March 30, 2014
Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type ...
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Journal ArticleCell Rep · January 16, 2014
Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell ...
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Journal ArticlePLoS One · 2014
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal bra ...
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Journal ArticleNature Genetics · January 1, 2014
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ...
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Journal ArticleNeuro Oncol · January 2014
BACKGROUND: A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting âĨ6 months and progression-free survival. METHODS: Thirty-five e ...
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Journal ArticleActa Neuropathologica · December 1, 2013
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not ...
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ConferenceCancer · December 1, 2013
BACKGROUND: The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinote ...
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Journal ArticleActa Neuropathol · December 2013
Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not ...
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Journal ArticleOncotarget · November 2013
KMT2D (lysine (K)-specific methyltransferase 2D), formerly named MLL2 (myeloid/lymphoid or mixed-lineage leukemia 2, also known as ALR/MLL4), is a histone methyltransferase that plays an important role in regulating gene transcription. In particular, it ta ...
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Journal ArticleLancet Oncol · November 2013
BACKGROUND: Recurrent medulloblastoma is a therapeutic challenge because it is almost always fatal. Studies have confirmed that medulloblastoma consists of at least four distinct subgroups. We sought to delineate subgroup-specific differences in medullobla ...
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Journal ArticleCell · October 10, 2013
We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature recept ...
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Journal 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 ...
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Journal ArticleNat Genet · October 2013
Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma ...
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Journal ArticleClin Cancer Res · September 15, 2013
PURPOSE: Tumor-infiltrating lymphocytes (TIL) have prognostic significance in many cancers, yet their roles in glioblastoma have not been fully defined. We hypothesized that TILs in glioblastoma are associated with molecular alterations, histologies, and s ...
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Journal ArticleClin Cancer Res · September 1, 2013
PURPOSE: The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive wi ...
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Journal 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, ...
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Journal ArticleJ Neurosurg · August 2013
Intracranial dermoid cysts are rare congenital lesions that typically occur in the cisternal spaces. However, exceptionally rare cases of intraaxial involvement have been reported, with only 8 cases having been described in the literature. The authors repo ...
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Journal ArticleJ Neurooncol · August 2013
Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized th ...
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Journal ArticleProc Natl Acad Sci U S A · April 9, 2013
Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thala ...
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Journal ArticleOncotarget · April 2013
A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric ...
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Journal ArticleCell · March 28, 2013
Glioblastomas (GBMs) are highly vascular and lethal brain tumors that display cellular hierarchies containing self-renewing tumorigenic glioma stem cells (GSCs). Because GSCs often reside in perivascular niches and may undergo mesenchymal differentiation, ...
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Journal ArticleJ Clin Neurosci · March 2013
The rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently described, rare, and distinct tumor of the glioneuronal family. The presentation, natural history, and treatment response of these tumors has been unclear as there are no s ...
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Journal ArticleClin Cancer Res · February 15, 2013
PURPOSE: Increased mitogenic signaling and angiogenesis, frequently facilitated by somatic activation of EGF receptor (EGFR; ErbB1) and/or loss of PTEN, and VEGF overexpression, respectively, drive malignant glioma growth. We hypothesized that patients wit ...
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Journal ArticleCancer Res · January 15, 2013
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Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually a ...
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Journal ArticleNature Genetics · 2013
Glioblastoma is one of the most challenging forms of cancer to treat. Here we describe a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma ...
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Journal ArticlePLoS One · 2013
Infiltration of myeloid cells in the tumor microenvironment is often associated with enhanced angiogenesis and tumor progression, resulting in poor prognosis in many types of cancer. The polypeptide chemokine PK2 (Bv8, PROK2) has been shown to regulate mye ...
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Journal ArticleAnn Neurol · November 2012
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OBJECTIVE: Glioblastomas (GBMs) are lethal cancers that display cellular hierarchies parallel to normal brain. At the apex are GBM stem cells (GSCs), which are relatively resistant to conventional therapy. Interactions with the adjacent perivascular niche ...
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Journal ArticleProc Natl Acad Sci U S A · October 23, 2012
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Myeloid/lymphoid or mixed-lineage leukemia (MLL)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription. MLL genes are frequently mutated in human cancers. Unlike MLL1, MLL2 (also know ...
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Journal ArticleCancer · October 1, 2012
BACKGROUND: We evaluated the efficacy of imatinib plus hydroxyurea in patients with progressive/recurrent low-grade glioma. METHODS: A total of 64 patients with recurrent/progressive low-grade glioma were enrolled in this single-center study that stratifie ...
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Journal ArticleJ Neurooncol · September 2012
A pilot study to investigate the feasibility of the addition of intrathecal (IT) mafosfamide to a regimen of concomitant multi-agent systemic chemotherapy followed by conformal radiation therapy (RT) for children <3 years with newly diagnosed embryonal CNS ...
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Journal ArticleCancer · September 1, 2012
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BACKGROUND: Primary tumors of the spinal cord, spinal meninges, and cauda equina are relatively rare, and a paucity of population-based data exist on tumors in these sites. This study intends to augment the current literature by examining incidence of thes ...
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Journal ArticleNature · August 2, 2012
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Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogene ...
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Journal ArticleJ Neurooncol · August 2012
Intracranial meningiomas are often indolent tumors which typically grow over years to decades. Nonetheless, meningiomas that progress after maximum safe resection and radiation therapy pose a significant therapeutic challenge and effective therapies have y ...
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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 ...
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Journal ArticleOncotarget · July 2012
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Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequen ...
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Journal ArticleJ Neurooncol · March 2012
We evaluated the efficacy of carboplatin, irinotecan, and bevacizumab among bevacizumab-naÃŊve, recurrent glioblastoma (GBM) patients in a phase 2, open-label, single arm trial. Forty eligible patients received carboplatin (area under the plasma curve [AUC] ...
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Journal Article · March 1, 2012
Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In ...
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Journal ArticleCancer Cell · February 14, 2012
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Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit overexpression or amplification of the MYC oncogene (c-MYC) usually have an extremely poor prognosis, but there are no animal models of this subtype of ...
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Journal ArticleJ Neurooncol · February 2012
To estimate the sustained (âĨ8 weeks) objective response rate in pediatric patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or brainstem gliomas (BSG, Stratum B) treated with the combination of O6-benzylguanine (O6BG) and temozolom ...
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Journal ArticleMol Cancer Res · February 2012
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Glioblastoma is universally fatal because of its propensity for rapid recurrence due to highly migratory tumor cells. Unraveling the genomic complexity that underlies this migratory characteristic could provide therapeutic targets that would greatly comple ...
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Chapter · January 1, 2012
Brain tumor biomarkers have long been used as diagnostic tools; they are now finally being brought to bear as therapeutic elements in the fight against brain cancer. Because of the heterogeneity of glial brain tumors, it is clear that no one marker will ev ...
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Journal ArticlePLoS One · 2012
BACKGROUND: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2RÎą/CD25) can enhance anti-tumor immunotherapy ...
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Journal ArticleCurr Radiopharm · January 2012
PURPOSE: Chloroquine has demonstrated high affinity for aldehyde dehydrogenase 1A1 (ALDH1), an enzyme expressed in the highly tumorigenic CD133+ brain tumor initiating subpopulation. The purpose of this study is to report the novel synthesis of a chloroqui ...
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Journal ArticleNucl Med Biol · January 2012
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INTRODUCTION: Malignant glioma remains a significant therapeutic challenge, and immunotherapeutics might be a beneficial approach for these patients. A monoclonal antibody (MAb) specific for multiple molecular targets could expand the treatable patient pop ...
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Journal 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 ...
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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 ...
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Journal ArticleBlood · September 15, 2011
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Lymphodepletion augments adoptive cell transfer during antitumor immunotherapy, producing dramatic clinical responses in patients with malignant melanoma. We report that the lymphopenia induced by the chemotherapeutic agent temozolomide (TMZ) enhances vacc ...
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Journal ArticleScience · September 9, 2011
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Oligodendrogliomas are the second most common malignant brain tumor in adults and exhibit characteristic losses of chromosomes 1p and 19q. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven tumors. Among ot ...
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Journal ArticleCell Death Dis · September 1, 2011
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Malignant gliomas contain a population of self-renewing tumorigenic stem-like cells; however, it remains unclear how these glioma stem cells (GSCs) self-renew or generate cellular diversity at the single-cell level. Asymmetric cell division is a proposed m ...
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Journal ArticleArch Pathol Lab Med · August 2011
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CONTEXT: Medulloblastomas (MBs) and atypical teratoid/rhabdoid tumors (AT/RTs) arising in infants and children can be difficult to distinguish; however, histologic characterization is prognostically important. OBJECTIVE: To determine histologic and phenoty ...
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Journal ArticleScience · July 22, 2011
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The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres and other genomic sites. Because inactivating mutations of these genes are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status of ...
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Journal ArticleCell · July 8, 2011
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Malignant gliomas are aggressive brain tumors with limited therapeutic options, and improvements in treatment require a deeper molecular understanding of this disease. As in other cancers, recent studies have identified highly tumorigenic subpopulations wi ...
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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 ...
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Journal ArticleCell Death Differ · May 2011
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Malignant gliomas are lethal cancers that display cellular hierarchies with cancer stem cells at the apex. Glioma stem cells (GSCs) are not uniformly distributed, but rather located in specialized niches, suggesting that the cancer stem cell phenotype is r ...
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Journal ArticleCancer Cell · April 12, 2011
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Glioblastomas display cellular hierarchies containing tumor-propagating glioblastoma stem cells (GSCs). STAT3 is a critical signaling node in GSC maintenance but molecular mechanisms underlying STAT3 activation in GSCs are poorly defined. Here we demonstra ...
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Journal ArticleJ Natl Compr Canc Netw · April 2011
Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth fa ...
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Journal ArticleNeuro Oncol · March 2011
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Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic c ...
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Journal ArticleScience · January 28, 2011
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Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and micro ...
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Journal ArticleJ Oncol · 2011
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Glioblastoma (WHO Grade IV) is both the most common primary brain tumor and the most malignant. Advances in the understanding of the biology of the tumor are needed in order to obtain a clearer picture of the mechanisms driving these tumors. To neuropathol ...
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Journal ArticleCancer · January 1, 2011
Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and are often encountered by non-neurosurgeons. These lesions typically present as enlarging, painless, benign masses that can be surgically cured. Imaging is critical for defining ...
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Journal ArticleJ Neurooncol · January 2011
Sorafenib, an oral VEGFR-2, Raf, PDGFR, c-KIT and Flt-3 inhibitor, is active against renal cell and hepatocellular carcinomas, and has recently demonstrated promising activity for lung and breast cancers. In addition, various protracted temozolomide dosing ...
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Journal ArticlePLoS One · 2011
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High-grade gliomas (World Health Organization grade III anaplastic astrocytoma and grade IV glioblastoma multiforme), the most prevalent primary malignant brain tumors, display a cellular hierarchy with self-renewing, tumorigenic cancer stem cells (CSCs) a ...
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Journal ArticleNeuro Oncol · December 2010
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Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling are established contributors to malignant glioma (MG) biology. We, therefore, evaluated bevacizumab, a humanized anti-VEGF monoclonal antibody, in combination w ...
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Journal ArticleBMC Dev Biol · November 18, 2010
BACKGROUND: Ganglioside biosynthesis occurs through a multi-enzymatic pathway which at the lactosylceramide step is branched into several biosynthetic series. Lc3 synthase utilizes a variety of galactose-terminated glycolipids as acceptors by establishing ...
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Journal ArticleJ Clin Oncol · November 1, 2010
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PURPOSE: Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed ...
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Journal ArticleBMC Cancer · September 1, 2010
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BACKGROUND: Glioblastoma multiforme (GBM) is refractory to conventional therapies. To overcome the problem of heterogeneity, more brain tumor markers are required for prognosis and targeted therapy. We have identified and validated a promising molecular th ...
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Journal ArticleEndocr Pathol · September 2010
The objective of the study was to assess O(6)-methylguanine-DNA methyltransferase (MGMT) immunoreactivity in pituitary adenomas of silent subtype 3 as a potential indicator of temozolomide susceptibility. The Mayo Clinic Anatomic Pathology Database was sea ...
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Journal ArticleNeuro Oncol · September 2010
Glioblastoma multiforme (GBM) is one of the deadliest tumors afflicting humans, and the mechanisms of its onset and progression remain largely undefined. Our attempts to elucidate its molecular pathogenesis through DNA copy-number analysis by genome-wide d ...
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Journal ArticleInt J Cancer · August 1, 2010
Multidrug resistance protein 3 (MRP3), a multidrug resistance protein identified by serial analysis of gene expression as a glioblastoma multiforme (GBM)-associated molecule, is highly expressed in GBM, but not in normal brain cells. Thus, MRP3 is a candid ...
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Journal ArticleOncotarget · August 2010
The glioblastoma genome displays remarkable chromosomal aberrations, which harbor critical glioblastoma-specific genes contributing to several oncogenetic pathways. To identify glioblastoma-targeted genes, we completed a multifaceted genome-wide analysis t ...
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Journal ArticleBiochem Biophys Res Commun · July 30, 2010
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Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+to NADPH). IDH1/2 were recently identified as mutated in a ...
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Journal ArticleJ Neurooncol · 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 ...
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Journal ArticleCell Stem Cell · May 7, 2010
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Cancer stem cells (CSCs) are a subpopulation of tumor cells suggested to be critical for tumor maintenance, metastasis, and therapeutic resistance. Prospective identification and targeting of CSCs are therefore priorities for the development of novel thera ...
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Journal ArticleCase Rep Oncol · April 8, 2010
Hemangiopericytoma (HPC) is a rare sarcomatous tumor arising from pericytes, a support cell found in blood vessels. These tumors can occur throughout the body, particularly in the lower extremities and retroperitoneum. In rare circumstances, HPCs can arise ...
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Journal ArticleJ Neurosurg Pediatr · April 2010
Cerebrospinal fluid overproduction resulting in communicating hydrocephalus is observed in patients who have choroid plexus papilloma or choroid plexus carcinoma. Less often, patients with these conditions have diffuse villous hyperplasia. Prior studies re ...
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Journal ArticlePLoS Biol · February 23, 2010
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Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioblastoma stem cells (GSCs). GSCs are regulated by molecular pathways distinct from the bulk tumor that may be useful therapeutic targets. We deter ...
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Journal ArticleBiochem Biophys Res Commun · January 1, 2010
The lacto-series gangliosides 3'-isoLM1 and 3',6'-isoLD1 have been identified as tumor-associated antigens whose formation is initiated by the Lc3-synthase. Until now, high-affinity IgG monoclonal antibodies (mAbs) against 3'-isoLM1 and 3',6'-isoLD1, which ...
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Journal ArticleGenes Cancer · January 1, 2010
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Recombinant erythropoietin (EPO) is a growth factor used in the treatment of chemotherapy-induced anemia, but recent studies suggest that EPO may accelerate cancer growth. Although several cancers express EPO receptors (EPORs), the mechanism by which EPOR ...
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Journal ArticleCancer Res · January 1, 2010
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OTX2 is a developmentally regulated transcription factor involved in early morphogenesis of the central nervous system. This gene is amplified and overexpressed in medulloblastoma cell lines, but the nature and extent of its genetic alterations in primary ...
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Journal 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) ...
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Journal ArticleCancer Biomark · 2010
Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In ...
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Journal ArticleBiochem Biophys Res Commun · December 18, 2009
IDH1 (isocitrate dehydrogenase 1) mutations have been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas as well as secondary glioblastomas. In contrast, primary glioblastomas very rarely contain ...
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Journal ArticleBr J Cancer · December 15, 2009
BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 ...
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Journal ArticleHybridoma (Larchmt) · December 2009
Somatostatin receptor 2 (SSTR2) is expressed by most medulloblastomas (MEDs). We isolated monoclonal antibodies (MAbs) to the 12-mer (33)QTEPYYDLTSNA(44), which resides in the extracellular domain of the SSTR2 amino terminus, screened the peptide-bound MAb ...
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Journal 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 ...
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Journal ArticleCancer Res · December 1, 2009
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Glioblastoma multiforme is the most prevalent type of adult brain tumor and one of the deadliest tumors known to mankind. The genetic understanding of glioblastoma multiforme is, however, limited, and the molecular mechanisms that facilitate glioblastoma m ...
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Journal ArticleCell Cycle · October 15, 2009
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Glioblastomas are highly lethal cancers that contain cellular hierarchies with self-renewing cancer stem cells that can propagate tumors in secondary transplant assays. The potential significance of cancer stem cells in cancer biology has been demonstrated ...
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Journal ArticleStem Cells · October 2009
Glioblastomas are the most common and most lethal primary brain tumor. Recent studies implicate an important role for a restricted population of neoplastic cells (glioma stem cells (GSCs)) in glioma maintenance and recurrence. We now demonstrate that GSCs ...
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Journal ArticleBrain Pathol · October 2009
Given the highly infiltrative growth pattern of malignant glioma and the lack of specificity associated with currently available treatment regimens, alternative strategies designed to eradicate cancer cells while limiting collateral toxicity in normal tiss ...
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Journal ArticleBrain Pathol · October 2009
Epidermal growth factor receptor (EGFR) is commonly affected in cancer, generally in the form of an increase in DNA copy number and/or as mutation variants [e.g., EGFR variant III (EGFRvIII), an in-frame deletion of exons 2-7]. While detection of EGFR aber ...
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Journal ArticleNeuro Oncol · October 2009
This phase I clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG) was designed to determine the maximum tolerated dose (MTD) and toxicity of three different 5-day dosing regimens of temozolomide (TMZ) in combination ...
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Journal ArticleNucl Med Biol · August 2009
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INTRODUCTION: Carcinomatous meningitis (CM) is a devastating disease characterized by the dissemination of malignant tumor cells into the subarachnoid space along the brain and spine. Systemic treatment with monoclonal antibody (mAb) trastuzumab can be eff ...
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Journal ArticleBrain Pathol · July 2009
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Chordoid gliomas are rare, slow-growing neoplasms of the anterior third ventricle. We reported a case of chordoid glioma in a 41-year-old man with obstructive hydrocephalus. Histologically, the tumor consisted of polygonal epithelioid cells admixed with el ...
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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 ...
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Journal ArticleCancer Cell · June 2, 2009
Glioblastomas are lethal cancers characterized by florid angiogenesis promoted in part by glioma stem cells (GSCs). Because hypoxia regulates angiogenesis, we examined hypoxic responses in GSCs. We now demonstrate that hypoxia-inducible factor HIF2alpha an ...
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Journal ArticleJ Clin Oncol · March 10, 2009
PURPOSE: This phase II trial was designed to define the role of O(6)-benzylguanine (O(6)-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administerin ...
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Journal ArticleN Engl J Med · February 19, 2009
BACKGROUND: A recent genomewide mutational analysis of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that wer ...
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Journal ArticleCancer Cell · February 3, 2009
The growth of many cancers depends on self-renewing cells called cancer stem cells or tumor-propagating cells (TPCs). In human brain tumors, cells expressing the stem cell marker CD133 have been implicated as TPCs. Here we show that tumors from a model of ...
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Journal ArticleClin Cancer Res · February 1, 2009
PURPOSE: This phase II trial was designed to define the efficacy of Gliadel wafers in combination with an infusion of O6-benzylguanine (O6-BG) that suppresses tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in patients with recurrent glioblastoma m ...
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Journal ArticlePediatr Neurosurg · 2009
Hypothalamic hamartomas (HHs) are congenital, benign masses in the hypothalamus and tuber cinereum that may cause central precocious puberty and gelastic seizures. Nodules of small neurons are thought to be a universal feature of the microarchitecture of H ...
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Journal ArticleStem Cells · December 2008
Malignant brain tumors are among the most lethal cancers, and conventional therapies are largely limited to palliation. Novel therapies targeted against specific molecular pathways may offer superior efficacy and less toxicity than conventional therapies, ...
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Journal ArticleNature · October 23, 2008
Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dim ...
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Journal ArticleNeuro Oncol · October 2008
The efficacy of high-dose chemotherapy (HDC) or standard salvage therapy was evaluated in patients with recurrent medulloblastoma (MBL) using retrospective chart review of all patients with recurrent MBL treated at Duke University Medical Center between 19 ...
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Journal ArticleScience · September 26, 2008
Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleot ...
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Journal ArticleCancer Res · August 1, 2008
Malignant gliomas are lethal cancers that display striking cellular heterogeneity. A highly tumorigenic glioma tumor subpopulation, termed cancer stem cells or tumor-initiating cells, promotes therapeutic resistance and tumor angiogenesis. Therefore, targe ...
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Journal ArticleClin Cancer Res · August 1, 2008
PURPOSE: A major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temo ...
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Journal ArticleArch Pathol Lab Med · June 2008
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CONTEXT: The World Health Organization (WHO) recently published its 4th edition of the classification of tumors of the central nervous system, incorporating a substantial number of important changes to the previous version (WHO 2000). The new WHO classific ...
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Journal ArticleNeuro Oncol · June 2008
The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brai ...
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Journal ArticleNeuro Oncol · June 2008
We determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate, an inhibitor of the receptor tyrosine kinases platelet-derived growth factor receptor (PDGFR), the proto-oncogene product c-kit, and the fusion protein Bc ...
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Journal ArticleNeuro Oncol · April 2008
The purpose of this study was to determine the feasibility and assess the efficacy and toxicity, among newly diagnosed malignant glioma patients, of administering (131)I-labeled murine antitenascin monoclonal antibody 81C6 ((131)I-81C6) into a surgically c ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · March 2008
Epidemiologists routinely conduct centralized single pathology reviews to minimize interobserver diagnostic variability, but this practice does not facilitate the combination of studies across geographic regions and institutions where diagnostic practices ...
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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 ...
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Journal ArticleJ Neurosurg · February 2008
OBJECT: Diffusely infiltrating astrocytomas are the most common primary brain tumors. As a group, they demonstrate an inherent tendency toward malignant progression. Histological grading using the guidelines of the World Health Organization (WHO) remains t ...
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Journal ArticleJ Clin Oncol · January 10, 2008
PURPOSE: The combination of a vascular endothelial growth factor (VEGF) -neutralizing antibody, bevacizumab, and irinotecan is associated with high radiographic response rates and improved survival outcomes in patients with recurrent malignant gliomas. The ...
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Journal ArticleJ Toxicol Environ Health A · 2008
Splenda is comprised of the high-potency artificial sweetener sucralose (1.1%) and the fillers maltodextrin and glucose. Splenda was administered by oral gavage at 100, 300, 500, or 1000 mg/kg to male Sprague-Dawley rats for 12-wk, during which fecal sampl ...
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Journal ArticleJ Nucl Med · January 2008
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UNLABELLED: alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of th ...
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Journal ArticlePLoS One · 2008
BACKGROUND: Malignant gliomas rank among the most lethal cancers. Gliomas display a striking cellular heterogeneity with a hierarchy of differentiation states. Recent studies support the existence of cancer stem cells in gliomas that are functionally defin ...
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Journal ArticleAm J Surg Pathol · January 2008
Choroid plexus papilloma may display unusual histologic features, but the presence of neuronal differentiation at the light microscopic level has not yet been described. We thus report a choroid plexus papilloma with neuropil-like islands located within th ...
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Journal ArticleArch Pathol Lab Med · October 2007
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CONTEXT: Patients with glioblastoma (astrocytoma, World Health Organization grade IV) exhibit 2-year survival rates of less than 20% despite significant advances in therapeutic options available to patients. Epidermal growth factor receptor (EGFR) hyperexp ...
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Journal ArticleClin Cancer Res · September 15, 2007
PURPOSE: The combination of temozolomide and irinotecan has preclinical schedule-dependent synergy against neuroblastoma but is not curative for relapsed high-risk patients. We hypothesized that the DNA repair protein methylguanine-DNA methyltransferase (M ...
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Journal ArticleNucl Med Biol · May 2007
INTRODUCTION: The neurohistological findings in patients treated with targeted beta emitters such as (131)I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting ...
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Journal 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 ...
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Journal ArticlePediatr Neurosurg · 2007
The authors report an unusual case of adamantinomatous craniopharyngioma occurring in isolation in the cerebellopontine angle of a 12-year-old female. The patient presented with a 1-year history of nausea, vomiting, and headache. MRI revealed a left cerebe ...
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Journal ArticleNature · December 7, 2006
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Ionizing radiation represents the most effective therapy for glioblastoma (World Health Organization grade IV glioma), one of the most lethal human malignancies, but radiotherapy remains only palliative because of radioresistance. The mechanisms underlying ...
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Journal ArticleCancer · November 1, 2006
BACKGROUND: An open-label Phase II study of oxaliplatin was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB), supratentorial primitive neuroectodermal tumors (SPNET), and atypical teratoid rhabdoid ...
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Journal ArticleCancer Chemother Pharmacol · November 2006
PURPOSE: Tumor resistance to alkylating agents such as carmustine (BCNU) has been found to be associated with intracellular expression of O6-methylguanine-DNA methyltransferase (MGMT). Administration of O6-benzylguanine (O6-BG), a substrate that inactivate ...
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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 ...
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Journal ArticleMol Cancer Ther · October 2006
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Promoter hypermethylation of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to co ...
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Journal ArticleCancer Res · September 1, 2006
Malignant gliomas are highly proliferative and angiogenic cancers resistant to conventional therapies. Although RAS and RAF mutations are uncommon in gliomas, RAS activity is increased in gliomas. Additionally, vascular endothelial growth factor and its co ...
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Journal ArticleCancer Res · August 15, 2006
Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical tumor subpopulations within gliomas share characteristics with neural stem cells. We examined the potential of stem cell-like glioma cells (SCLGC) to support tumor angiogenesis ...
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Journal ArticleJ Nucl Med · June 2006
UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine ...
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Journal ArticleArch Pathol Lab Med · May 2006
CONTEXT: A significant difficulty that pathologists encounter in arriving at a correct diagnosis is related to the way information from various sources is processed and assimilated in context. OBJECTIVE: These issues are addressed by the science of cogniti ...
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Journal ArticleJ Neurooncol · April 2006
The role of chemotherapy in the treatment of high-grade gliomas in children is unclear. Early reports were suggestive of improved outcome in children with high-grade glioma with the addition of chemotherapy after surgery and radiation therapy. Subsequent s ...
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Journal ArticleClin Cancer Res · February 1, 2006
PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among pat ...
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Book · January 1, 2006
This is the leading international professional reference text that also serves as a bench book, describing all aspects of the pathology of brain tumours - genetics, molecular biology, epidemiology, morphology, immunohistochemistry, diagnostic criteria and ...
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Journal ArticleJ Clin Oncol · January 1, 2006
PURPOSE: To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients. PATIENTS AND METHODS: In this phase II trial, 100 mCi of 131I ...
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Journal 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 ...
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Journal ArticleClin Cancer Res · November 15, 2005
PURPOSE: Primary central nervous system (CNS) tumors represent a diverse group of tumor types with heterogeneous molecular mechanisms that underlie their formation and maintenance. CNS tumors depend on angiogenesis and often display increased activity of E ...
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Journal ArticleCancer · October 15, 2005
BACKGROUND: Allelic losses of 1p and 19q arms correlate with the oligodendroglial phenotype as well as with sensitivity to radiotherapy and chemotherapy. Furthermore, the DNA repair gene, methylguanine methyltransferase (MGMT), is diminished in 80% of olig ...
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Journal ArticleCancer · October 1, 2005
BACKGROUND: The authors determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan (CPT-11), a topoisomerase I inhibitor, when administered with temozolomide among patients with recurrent malignant glioma (MG). METHODS: Pati ...
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Journal ArticleJ Clin Oncol · October 1, 2005
PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The ...
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Journal ArticleJ Nucl Med · June 2005
UNLABELLED: The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into su ...
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Journal ArticleCancer Res · May 15, 2005
Despite the strikingly grave prognosis for older patients with glioblastomas, significant variability in patient outcome is experienced. To explore the potential for developing improved prognostic capabilities based on the elucidation of potential biologic ...
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Journal ArticleJ Neuropathol Exp Neurol · April 2005
The Accreditation Council for Graduate Medical Education (ACGME) has defined 6 core competencies for all physicians: patient care; medical knowledge; practice-based learning and improvement; interpersonal and communication skills; professionalism; and syst ...
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Journal ArticleCancer Res · February 1, 2005
Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93 ...
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Journal ArticleNeuro Oncol · January 2005
Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to tra ...
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Journal ArticleMol Cancer Ther · January 2005
Malignant gliomas are highly lethal tumors that display striking genetic heterogeneity. Novel therapies that inhibit a single molecular target may slow tumor progression, but tumors are likely not dependent on a signal transduction pathway. Rather, maligna ...
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Journal ArticleCancer Res · August 1, 2004
The phosphatidylinositol 3'-kinase pathway is activated in multiple advanced cancers, including glioblastomas, through inactivation of the PTEN tumor suppressor gene. Recently, mutations in PIK3CA, a member of the family of phosphatidylinositol 3'-kinase c ...
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Journal ArticleJ Mol Diagn · August 2004
Astrocytoma is comprised of a group of common intracranial neoplasms that are classified into four grades based on the World Health Organization histological criteria and patient survival. To date, histological grade, patient age, and clinical performance, ...
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Journal ArticleClin Neuropathol · 2004
Rare meningiomas have been described that contain eosinophilic inclusions that have a granular or granulofilamentous ultrastructure. We describe a 66-year-old woman who developed a planum sphenoidale meningioma. Histologically, the tumor was composed of me ...
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Journal ArticleJ Clin Oncol · January 1, 2004
PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an op ...
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Journal ArticleClin Neuropathol · 2004
OBJECTIVE: Extracranial subcutaneous masses involving the scalp and/or skull in young children are uncommon lesions that get excised by the neurosurgeon. Although the most common reported lesion is the dermoid cyst, our experience suggests that the spectru ...
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Journal ArticleVirology · December 20, 2003
The double-stranded (ds) RNA-activated protein kinase (PKR) plays an important role in control of viral infections and cell growth. We have studied the role of PKR in viral infection in mice that are defective in the PKR signaling pathway. Transgenic mice ...
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Journal ArticleClin Cancer Res · November 15, 2003
PURPOSE: The monoclonal antibody (MAb) trastuzumab (Herceptin) effectively treats HER2-overexpressing extracerebral breast neoplasms. Delivery of such macromolecule therapeutic agents to intracerebral metastases, however, is limited by the tight junctions ...
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Journal ArticleCancer · October 15, 2003
BACKGROUND: The 5-year survival rate for intracranial glioblastoma multiforme (GBM) has remained at 4-5% for the last 30 years, in spite of multiple randomized prospective trials. The authors hypothesized, based on the literature, that even this remarkably ...
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Journal ArticleJ Neurooncol · October 2003
TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maxim ...
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Journal ArticleJ Clin Oncol · June 1, 2003
PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initial ...
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Journal ArticleAm J Surg Pathol · April 2003
Anaplastic large cell lymphoma (ALCL) rarely occurs in the central nervous system. Although defined by its composition of large, pleomorphic, CD30-positive lymphocytes, ALCL is heterogeneous. Most are T cell but some are null cell. Most but not all have a ...
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Journal ArticleJ Clin Oncol · February 15, 2003
PURPOSE: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studi ...
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Journal ArticleInt J Radiat Oncol Biol Phys · November 15, 2002
PURPOSE: To establish the theoretical framework and study the feasibility of (211)At-labeled anti-tenascin chimeric 81C6 monoclonal antibody (mAb) as anti-vascular endoradiotherapy for the treatment of glioblastoma multiforme (GBM) tumors. METHODS AND MATE ...
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Journal ArticleClin Cancer Res · November 2002
Iressa (ZD1839) is a p.o.-active, selective, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways implicated in cancer cell proliferation, survival, and host-dependent processes promoting cancer gro ...
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Journal ArticleClin Cancer Res · June 2002
The November 2000 NIH report of the Brain Tumor Progress Review Group identified delivering and targeting therapeutic agents as a priority in the treatment of malignant brain tumors. For this reason, the seventh annual Blood-Brain Barrier Disruption Consor ...
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Journal ArticleCancer · May 15, 2002
BACKGROUND: Astrocytoma is a primary brain tumor that affects 20,000 Americans each year. To date, only age and histologic grade stand out as independent predictors of survival. There is now increased interest in the use of molecular markers as objective s ...
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Journal ArticleArch Pathol Lab Med · May 2002
CONTEXT: Brain tumors are the most common solid tumor in childhood, and medulloblastoma is the most common malignant brain tumor in this age group. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplifi ...
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Journal ArticleJ Clin Oncol · May 1, 2002
PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O(6)-alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent ...
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Journal ArticleNeuro Oncol · April 2002
A phase II study of irinotecan (CPT-11) was conducted at Duke University Medical Center, Durham, NC, to evaluate the activity of this agent in children with high-risk malignant brain tumors. A total of 22 children were enrolled in this study, including 13 ...
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Journal ArticleNeuro Oncol · April 2002
Cell lines and xenografts derived from medulloblastomas are useful tools to investigate the chromosomal changes in these tumors. Here we used G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridiz ...
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Journal ArticleJ Clin Oncol · March 1, 2002
PURPOSE: To assess the efficacy and toxicity of intraresection cavity (131)I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase ...
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Journal ArticleNeurosurgery · January 2002
OBJECTIVE: Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by D ...
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Journal ArticleClin Neuropathol · 2002
To ascertain if a carcinoma-like component within a fibroblastic meningioma represented a metastatic carcinoma to a meningioma or malignant progression, we employed traditional immunohistochemical methods as well as comparative genomic hybridization (CGH) ...
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Journal ArticleBrain Tumor Pathol · 2002
Advances in the immunohistochemical detection of neuron-specific and neuronal-associated antigens have resulted in the discovery of neuronal elements in certain primary human brain tumors. The results have been not only to expand what neuropathologists com ...
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Journal ArticleNeuroradiology · December 2001
Endodermal cysts are rare congenital intracranial lesions. Although histologically benign, they can become symptomatic as a result of mass effect and cause neurological deficits. We report a 30-year-old woman who presented with paresis of her right oculomo ...
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Journal ArticleActa Neuropathol · October 2001
Intracranial solitary fibrous tumors (SFTs) are typically dural-based, CD34-positive neoplasms of uncertain histogenesis. We examined ten cases of meninges obtained at autopsy from patients with no history of neurological illness, head trauma, or neurosurg ...
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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 ...
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Journal ArticleBrain Pathol · July 2001
The March COM: A 16 year old female presented with headaches and cerebellar dysfunction. MR images showed a mass lesion of the right cerebellar hemisphere with mass effect on the medulla. The mass exhibited a striated pattern of alternating isointense and ...
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Journal ArticleCancer Res · May 1, 2001
Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will require a better understanding of the molecular nature of these tumors. We, therefore, mimicked the most common genetic changes found in grade III-IV gliomas, disruption of the ...
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Journal ArticleArch Pathol Lab Med · May 2001
CONTEXT: Classic diagnostic neuropathologic teachings have cautioned against making the diagnosis of neoplasia in the presence of a macrophage population. The knowledge of macrophage distribution should prove useful when confronted with an infiltrating gli ...
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Journal ArticleJ Anat · April 2001
Facet capsule injury has been hypothesised as a mechanism for neck pain. While qualitative studies have demonstrated the proximity of neck muscles to the cervical facet capsule, the magnitude of their forces remains unknown owing to a lack of quantitative ...
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Journal ArticleJournal of Anatomy · 2001
Facet capsule injury has been hypothesised as a mechanism for neck pain. While qualitative studies have demonstrated the proximity of neck muscles to the cervical facet capsule, the magnitude of their forces remains unknown owing to a lack of quantitative ...
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Journal ArticleJ Clin Oncol · November 15, 2000
PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any ob ...
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Journal ArticleJ Clin Oncol · October 15, 2000
PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O(6) position of guanine. O(6)-benzylguanine ...
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Journal ArticleClin Cancer Res · October 2000
Intracerebral microinfusion (ICM) is an innovative technique of delivering therapeutic agents throughout large portions of the brain that circumvents the blood-brain barrier, minimizes systemic toxicity, and provides a homogeneous distribution of the infus ...
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Journal ArticleJ Histochem Cytochem · August 2000
Epidermal growth factor receptor (EGFR), its variant, EGFRvIII, and tenascin are glioma-associated antigens that are hyperexpressed by neoplastic glial cells relative to normal brain, making them attractive antigenic targets for immunotherapy. Preliminary ...
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Journal ArticleAnn Clin Lab Sci · July 2000
We report a rare case of the plasma cell variant of Castleman's disease confined to the leptomeninges in a 42-year-old female. Flow cytometry demonstrated a minor monoclonal kappa light chain population, and conventional Southern blotting confirmed clonal ...
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Journal ArticleActa Neuropathol · May 2000
Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pil ...
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Journal ArticleActa Neuropathol · April 2000
Loss of portions of chromosome 17p, usually through the formation of i(17qp) is a well-known finding in medulloblastomas. Loss of heterozygosity (LOH) studies, however, occasionally demonstrate loss of the more distal portions of 17p, a pattern which is mo ...
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Journal ArticleAJR Am J Roentgenol · March 2000
OBJECTIVE: The purpose of this study was to compare MR imaging features of gangliogliomas in children less than 10 years old with those seen in patients at least 10 years old. MATERIALS AND METHODS: Our study population consisted of 15 female patients and ...
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Journal ArticleNeuroradiology · March 2000
Cerebral sparganosis, a parasitic disease, rarely produces a chronic active inflammatory response in the brain. Clinically and radiographically the process may mimic a neoplasm. We report a 30-year-old man who underwent surgical exploration for a mass in t ...
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Journal ArticleInt J Radiat Oncol Biol Phys · March 1, 2000
PURPOSE: The objective of this study was to perform the dosimetry and evaluate the dose-response relationships in newly diagnosed patients with malignant brain tumors treated by direct injections of (131)I-labeled 81C6 monoclonal antibody (MAb) into surgic ...
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Journal ArticleJ Neuroimmunol · February 1, 2000
To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell line derived from an astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morp ...
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Journal ArticleMod Pathol · December 1999
Primary central nervous system lymphoma (PCNSL) is a rare disease that has been increasing in frequency. Clinical, histologic, and immunohistochemical data from 64 cases of PCNSL seen at Duke University Medical Center since 1968 were reviewed and tumors we ...
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Journal ArticleCancer Res · November 1, 1999
A public database, SAGEmap, was created as a component of the Cancer Genome Anatomy Project to provide a central location for depositing, retrieving, and analyzing human gene expression data. This database uses serial analysis of gene expression to quantif ...
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Journal ArticleAm J Surg Pathol · October 1999
The distinction between intracranial viral infections and inflammatory conditions requiring immunosuppression is important. Although specific laboratory reagents are readily available for some viruses, diagnosis of arbovirus infection is more difficult. Tr ...
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Journal ArticleInt J Radiat Oncol Biol Phys · September 1, 1999
PURPOSE: The antitenascin human/mouse chimeric monoclonal antibody labeled with the alpha-particle-emitting radionuclide 211At is of interest as an endoradiotherapeutic agent for the treatment of brain tumors. To facilitate the investigation of 211At-label ...
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Journal ArticleClin Cancer Res · September 1999
The incidence of neoplastic meningitis is on the rise. Neoplastic meningitis can result from a direct seeding of the neuraxis by primary brain tumors or by hematogeneous spread of systemic solid tumors. A frequent genetic alteration in primary brain tumors ...
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Journal ArticleAm J Pathol · August 1999
Oligodendroglial neoplasms are a subgroup of gliomas with distinctive morphological characteristics. In the present study we have evaluated a series of these tumors to define their molecular profiles and to determine whether there is a relationship between ...
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Journal ArticleClin Cancer Res · May 1999
Neoplastic meningitis (NM) results from leptomeningeal dissemination of cancers arising within the central nervous system or metastasizing to the leptomeninges from systemic neoplasms. The inability to produce therapeutic drug levels intrathecally (i.t.) w ...
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Journal ArticleDiagn Cytopathol · May 1999
The term "ancient" schwannoma was proposed for a group of neural tumors showing degenerative changes and marked nuclear atypia. Prior to the realization that the observed atypia was a regressive phenomenon, many of these lesions were erroneously diagnosed ...
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Journal ArticleJ Clin Oncol · May 1999
PURPOSE: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma. PATIENTS AND METHODS: Patients w ...
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Journal ArticleArch Pathol Lab Med · April 1999
BACKGROUND: From both epidemiologic and pathologic viewpoints, gangliogliomas exhibiting components of giant cell glioblastomas are extraordinary neoplasms. We report herein the case of a 6-year-old girl who presented initially with a World Health Organiza ...
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Journal ArticleAJR Am J Roentgenol · April 1999
OBJECTIVE: The purpose of this study was to correlate 18F-fluorodeoxyglucose positron emission tomography (PET) and MR imaging features of cerebral gangliogliomas before and after PET-MR image registration. CONCLUSION: After registration of PET and MR imag ...
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Journal ArticleCancer · March 1, 1999
BACKGROUND: Topotecan activity was evaluated for the treatment of malignant glioma. METHODS: Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan [AU: Please verify all dosages here and throu ...
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Journal ArticleHistopathology · February 1999
AIMS: We have reviewed immunohistochemically 17 paediatric medulloblastomas in order to determine if correlations exist that might be useful in subclassifying these tumours. METHODS AND RESULTS: The patient group included 11 children who had died (mean sur ...
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Journal ArticleClin Neuropathol · 1999
Meningiomas are primary meningeal based tumors of the central nervous system that rarely are located strictly within the fourth ventricle. We report a 72-year-old man operated upon for such a tumor. The pre-operative magnetic resonance images revealed a we ...
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Journal ArticleNeuro Oncol · January 1999
Morphologic criteria for diagnosing oligodendrogliomas and for classifying them as well-differentiated (World Health Organization grade II) and anaplastic (World Health Organization grade III) are well recognized. Nevertheless, applying these guidelines to ...
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Journal ArticleClin Neuropathol · 1999
We describe the case of a 7-year-old girl who was clinically diagnosed as having a pontine glioma based on magnetic resonance imaging studies. Neoplastic cells were identified upon cytologic examination of cerebrospinal fluid. Autopsy studies revealed an a ...
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Journal ArticleJ Neurooncol · 1999
The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated thr ...
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Journal ArticleJ Clin Oncol · December 1998
PURPOSE: We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA ...
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Journal ArticleJournal of Nuclear Medicine · December 1, 1998
After the intracavitary administration of 131l-labeled monoclonal antibody for treatment of primary brain tumors after surgical resection, a persistent rim of 18F-fluorodeoxyglucose (FDG) accumulation surrounding the cavity can be observed on PET. This rim ...
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Journal ArticleJ Neurosurg · November 1998
Intradural spinal teratoma is a rare tumor that can be associated with dysraphic defects. Although the origin of these tumors is traditionally thought to be secondary to primordial germ cells misplaced early in embryogenesis, the pathogenesis of intraspina ...
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Journal ArticleJ Clin Oncol · November 1998
PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy is the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which removes chlorethylation or methylation damage from the O6-position of guanine. O6-benzylguanine (O6-BG) is an ...
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Journal ArticleAm J Surg Pathol · October 1998
We describe the clinicopathologic features of nine cases of a unique papillary glioneuronal tumor (PGNT) exhibiting astrocytic as well as extensive and varied neuronal differentiation. The four male and five female patients studied ranged in age from 11 to ...
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Journal ArticleJ Neurooncol · October 1998
The biologic behavior of ependymomas is highly variable, and its correlation with histologic features is at best imprecise. This retrospective study attempted to correlate the malignant histologic characteristics of ependymomas with MIB-1 proliferation ind ...
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Journal ArticleJ Nucl Med · August 1998
UNLABELLED: After the intracavitary administration of 131I-labeled monoclonal antibody for treatment of primary brain tumors after surgical resection, a persistent rim of 18F-fluorodeoxyglucose (FDG) accumulation surrounding the cavity can be observed on P ...
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Journal ArticleJ Clin Oncol · June 1998
PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS ...
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Journal ArticleClin Cancer Res · June 1998
During replication, the primary function of the eukaryotic DNA mismatch repair (MMR) system is to recognize and correct mismatched base pairs within the DNA helix. Deficiencies in MMR have been reported previously in cases of hereditary nonpolyposis colore ...
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Journal ArticleNeurosurg Focus · April 15, 1998
In this study, the authors sought to investigate the response rate and toxicity of carboplatin in patients with progressive low-grade glioma (LGG). Thirty-two patients with progressive LGG were treated with carboplatin at a dosage of 560 mg/m(2). Treatment ...
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Journal ArticleMed Pediatr Oncol · February 1998
Seventeen patients less than or equal to 20 years of age with newly diagnosed (n = 10) or recurrent (n = 7) malignant gliomas (anaplastic astrocytoma and glioblastoma multiforme) were treated with cyclophosphamide in association with hematopoietic cytokine ...
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Journal ArticleClin Neuropathol · 1998
Twenty-nine months after surgery, irradiation, and systemic chemotherapy for a pineal mixed germ cell tumor, an 11-year-old Caucasian male developed a 3 cm dural based nodule in the occipital lobe that proved to be a solitary fibrous tumor by immunohistoch ...
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Journal ArticleCancer Res · October 1, 1997
The PTEN gene, located on 10q23, has recently been implicated as a candidate tumor suppressor gene in brain, breast and prostate tumors. In the present study, 123 brain tumors, including various grades and histological types of gliomas occurring in childre ...
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Journal ArticleCancer Res · September 15, 1997
The potential of therapeutic targeting of tumor cell surface epidermal growth factor receptors (EGFRs) by modified ligands or specific antibodies has been limited by the normal tissue distribution of the receptor. The identification and characterization of ...
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Journal ArticleCancer Genet Cytogenet · September 1997
In the present cytogenetic analysis of 116 pediatric brain tumors, chromosomal abnormalities were demonstrated in 44 cases, 48 cases revealed only 46,XX or 46,XY cells, and 24 cases were nonproductive. In contrast to studies of adult brain tumors in which ...
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Journal ArticleArch Pathol Lab Med · May 1997
OBJECTIVE: Malignant neoplasms exhibiting mixed populations of neuronal and glial cells occurring in the cerebral hemispheres of young adults and children are well recognized, but rare. A confusing array of diagnostic terms has arisen. We describe two pati ...
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Journal ArticleMed Pediatr Oncol · March 1997
Primary malignant rhabdoid tumor (PMRT) of the brain is a rare and recently described neoplasm of youth. We report magnetic resonance imaging (MRI), computed tomography (CT), and pathology of one case of PMRT in an adult which seeded along the needle track ...
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Journal ArticleMed Pediatr Oncol · February 1997
In recent years, major advances in the diagnosis and treatment of patients with brain tumors have been seen. Today, evaluation of the central nervous system almost always includes magnetic resonance imaging (MRI). The appearance of a new lesion on the MRI ...
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Journal ArticleAJNR Am J Neuroradiol · February 1997
We report the MR imaging findings in two patients with solitary craniocerebral plasmacytoma, a benign plasma cell tumor that can arise from the skull, the dura, or, rarely, the brain. In both patients, the lesion was extraaxial and nearly isointense with g ...
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Journal ArticleCancer Chemother Pharmacol · 1997
The prognosis for patients with malignant gliomas continues to be dismal. The high degree of resistance of gliomas to nitrosourea-based chemotherapy is one major factor in poor treatment outcome. The identification of O6-alkylguanine-DNA alkyltransferase ( ...
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Journal ArticleNeuroradiology · November 1996
Gliomatosis cerebri is a rare form of astrocytoma characterized by extreme infiltration of the brain structure in conjunction with a relative paucity of clinical findings. We describe the MRI findings in a patient with gliomatosis cerebri widely infiltrati ...
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Journal ArticleMed Pediatr Oncol · July 1996
Leptomeningeal dissemination of childhood pilocytic astrocytoma (PA) is a rare event with little information available regarding therapy. We report here four children with disseminated PA whom we treated with high doses of cyclophosphamide with clinical be ...
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Journal ArticleClin Cancer Res · June 1996
We aimed to determine the maximum tolerated dose (MTD) of 131I-labeled 81C6 in patients with leptomeningeal neoplasms or brain tumor resection cavities with subarachnoid communication and to identify any objective responses. 81C6 is a murine IgG monoclonal ...
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Journal ArticleMed Pediatr Oncol · June 1996
The outcome for patients with pineoblastoma has historically been very poor, with most patients dying of disseminated disease despite irradiation. Furthermore, the low incidence of this tumor has hindered progress toward defining better treatment strategie ...
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Journal ArticleJ Neuropathol Exp Neurol · May 1996
Childhood ependymomas exhibit epidemiologic, anatomic, histologic, and biologic features and distinguish them from other gliomas. Because of their propensity to grow in functionally sensitive regions of the brain, adequate tumor sampling for basic and ther ...
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Journal ArticleAJNR Am J Neuroradiol · April 1996
PURPOSE: To determine the MR features of spinal angiolipomas and to compare these findings with their histologic appearance. METHODS: The MR examinations of three patients with surgically proved angiolipomas were reviewed for tumor location and extent, sig ...
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Journal ArticleArch Pathol Lab Med · April 1996
The ganglion cell-containing tumors of the pituitary are rare lesions of undetermined histogenesis and nosology. A review of the literature revealed 42 such tumors, including the 3 cases described below. On the basis of this review, the tumors were divided ...
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Journal ArticleInt J Radiat Oncol Biol Phys · April 1, 1996
PURPOSE: The present study undertook to establish the dose (LD) of systematically administered (via tail vein) sodium [211At]astatide that would kill 10% (LD10) of exposed animals in two mouse models and to evaluate the resulting histologic lesions. METHOD ...
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Journal ArticleGenes Chromosomes Cancer · January 1996
Loss of heterozygosity at specific chromosomal locations has been taken as evidence of a tumor suppressor gene located in that area. We performed a genomic allelotyping study on 46 childhood brain tumors of different histopathological types in order to ide ...
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Journal ArticleClin Cancer Res · December 1995
LMB-1 (B3-LysPE38) is an immunotoxin composed of the tumor-reactive monoclonal antibody B3 and a genetically engineered form of Pseudomonas exotoxin. Monoclonal antibody B3 reacts with a carbohydrate epitope that is found on a number of solid tumors (e.g., ...
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Journal ArticleGlia · November 1995
Gliomas affect 15,000 to 17,000 Americans every year and carry a dismal prognosis. The potential of immunologically mediated diagnosis and therapy, although greatly enhanced since the advent of monoclonal antibodies, has not been fully realized due to sign ...
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Journal ArticlePediatr Radiol · November 1995
We report two cases of papillary meningioma in children. The MRI appearance of this special type of meningioma is described for the first time. Both lesions were dura based and associated with cystic components. We review the literature pertaining to this ...
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Journal ArticleCancer Res · September 1, 1995
Malignant gliomas will affect 15,000-17,000 Americans each year and carry a dismal prognosis. Adjuvant chemotherapy is hampered by inadequate drug delivery, systemic toxicity, and a markedly variable biological sensitivity. Intraarterial (i.a.) therapy may ...
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Journal ArticleAJNR Am J Neuroradiol · August 1995
We present a case of a giant cell reparative granuloma of the frontoethmoidal region that had a large intracranial extraaxial component and was studied with MR. Although rare, giant cell reparative granuloma can be suggested in the correct clinical setting ...
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Journal ArticleCancer Res · July 15, 1995
Despite molecular biological advances in understanding human cancers, translation into therapy has been less forthcoming; targeting neoplastic cells still requires that tumor-specific markers, preferably those on the cell surface, be identified. The epider ...
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OtherOncogene · June 1, 1995
The high incidence of loss of chromosome 10 alleles in glioblastoma multiforme suggests the presence on this chromosome of a tumor suppressor gene that is important in glioma tumorigenesis and progression. Our initial deletion mapping studies using restric ...
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Journal ArticleZhonghua Yi Xue Za Zhi (Taipei) · June 1995
Cerebral phaeohyphomycosis is used to describe the rare clinical syndrome of cerebral infection caused by dematiaceous (i.e. pigmented olivaceous-brown) fungi. It usually presents as brain abscess. In view of the rarity of this fungal infection and its cli ...
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Journal ArticleNeurosurgery · May 1995
A new model for human brain tumor uses the intracranial placement of tumor xenografts under transparent glass cranial windows in nude rats, which require no immunosuppression for tumor engraftment. Adult male nude rats underwent implantation of human anapl ...
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Journal ArticleArch Pathol Lab Med · April 1995
A case of an intracranial dermoid cyst containing shadow cells is presented. This case expands the group of lesions in which shadow cells, indicative of hair matrical differentiation, have been described. ...
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Journal ArticleProc Natl Acad Sci U S A · March 28, 1995
LMB-7 [B3(Fv)-PE38] is a single-chain immunotoxin constructed from the murine monoclonal antibody B3 and a truncated from of Pseudomonas exotoxin PE38. Antibody B3 recognizes a carbohydrate epitope found on solid tumors that frequently invade the intrathec ...
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Journal ArticleSpine (Phila Pa 1976) · March 1, 1995
STUDY DESIGN: An animal model of laminectomy in rats was used to study scar tissue formation around the spinal cord. Dexamethasone, in controlled-release form, was tested in this system for its ability to decrease fibrous tissue formation. OBJECTIVES: The ...
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Journal ArticleJ Neurooncol · 1995
DNA derived from medulloblastoma biopsies was analyzed to determine if deletions of the 17p region, mutations of the TP53 gene, or amplification of the c-myc, N-myc, EGFR (epidermal growth factor receptor), or MDM2 (murine double-minute-2) genes was indica ...
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Journal ArticleJ Neurooncol · 1995
The advent of monoclonal antibody (MAb) technology has made Ehrlich's postulate of the 'magic bullet' an attainable goal. Although specific localization of polyvalent antibodies to human gliomas was demonstrated in the 1960s, the lack of specific, high aff ...
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OtherJ Comput Assist Tomogr · 1995
We report development of an intracranial epidermoid cyst 2 years after a depressed skull fracture. The epidermoid cyst is presumed to be the result of introduction of epidermal elements at the time of trauma. Post-traumatic intracranial epidermoid cysts ar ...
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Journal ArticleCancer Res · September 1, 1994
We report the activity and toxicity of intrathecal melphalan in the treatment of human neoplastic meningitis in the subarachnoid space of athymic nude rats. Animals received injections via chronic indwelling subarachnoid catheters with 5 x 10(5) or 5 x 10( ...
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Journal ArticleCancer Res · September 1, 1994
Because of their short range and high linear energy transfer, alpha-particles may be particularly effective in the treatment of neoplastic meningitis. Monoclonal antibody 81C6 was labeled with alpha-particle-emitting 211At using N-succinimidyl3-[211At]asta ...
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Journal ArticleBrain Pathol · July 1994
The immunohistochemical localization of glial fibrillary acidic protein has proven its utility in the histologic identification of benign astrocytes and neoplastic cells of glial lineage in the central nervous system. Its application in the developing nerv ...
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Journal ArticleCancer Res · March 1, 1994
Glial tumors of all grades and histological types from 72 adults and 48 children were analyzed for mutations of the TP53 gene, loss of heterozygosity (LOH) for 17p, and accumulation of TP53 protein to determine whether the incidence and type of TP53 altera ...
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Journal ArticleMol Chem Neuropathol · 1994
A library of epitope-defined antiganglioside monoclonal antibodies has been used to analyze the ganglioside phenotype of human glioma cell lines, rodent xenografts derived from them, and a separate panel of human glioma biopsies by multiple quantitative an ...
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Journal ArticleClin Neuropathol · 1994
Conventional treatment for medulloblastoma includes surgical resection followed by craniospinal irradiation, with the potential risk of subsequent radiotherapy-induced secondary neoplasms. We report a 23-year-old woman previously irradiated nine years earl ...
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Journal ArticleMed Pediatr Oncol · 1994
Magnetic resonance imaging (MRI) is becoming the method of choice for evaluation of central nervous system tumors. However, the sensitivity of this modality raises concern that new lesions in patients previously diagnosed with a brain tumor may not necessa ...
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Journal ArticleCancer Res · May 15, 1993
The addition of chemotherapy, notably using nitrosoureas, in the treatment of patients with glioblastoma multiforme has resulted in only modest improvements in long-term patient survival over the use of surgical intervention and irradiation alone. Intraart ...
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Journal ArticleCancer Res · January 1, 1993
Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuA ...
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OtherJ Comput Assist Tomogr · 1993
Gangliocytomas are rare CNS tumors that occur in children and young adults. We present a case of a cerebellar gangliocytoma with invasion of the cervical spinal cord demonstrated on MR. Radiographic differentiation of gangliocytomas from other ganglion cel ...
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Journal ArticleCancer Research · January 1, 1993
The addition of chemotherapy, notably using nitrosoureas, in the treatment of patients with glioblastoma multiforme has resulted in only modest improvements in long-term patient survival over the use of surgical intervention and irradiation alone. Intraart ...
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Journal ArticleClin Lab Med · March 1990
The focus of this review has been the application of MAbs as adjuncts in the interpretation of cytology specimens. It is evident that most if not all of the MAbs studied thus far are neither completely tumor-specific nor -sensitive; however, when used to a ...
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Journal ArticleNeurosurgery · May 1988
Adipose tissue in the filum terminale is frequently associated with tethering of the spinal cord in patients with spina bifida occulta. We recently saw a patient with low back pain and no spina bifida occulta, in whom adipose tissue was noted in the area o ...
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Journal ArticleRadiology · October 1987
Thirteen patients with intracerebral malignant melanoma underwent high-field-strength (1.5-T) magnetic resonance (MR) imaging. The images were correlated with computed tomography (CT) scans (n = 7) and surgical specimens (n = 7). Most commonly, these lesio ...
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Journal ArticleJ Neuroimmunol · May 1987
Radioiodinated murine monoclonal antibodies (Mabs) 81C6, Me 1-14, C12, D12, and E9, made against or reactive with human gliomas but not normal brain, and Mab UJ13A, a pan-neuroectodermal Mab reactive with normal human glial and neural cells, were evaluated ...
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Journal ArticleCancer · April 1, 1987
To determine the prognostic significance of histologic variables in oligodendroglial neoplasms, the presence and degree of 15 such variables were correlated with postoperative survival rates in 71 patients. By univariate analysis, prognostically significan ...
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Journal ArticleRadiology · November 1986
The mechanism of cavernous sinus involvement by metastatic carcinoma from a facial primary tumor is poorly understood. The lack of lymphatic and obvious direct extension implicate either a vascular or perineural method of spread. The authors describe four ...
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Journal ArticleCancer Res · November 1986
Multiple fusions following immunization of athymic mice with the extensively characterized human glioma cell line D-54 MG resulted in the selection of several antibodies (Mabs) highly reactive with tumors of neuroectodermal origin and unreactive with norma ...
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Journal ArticleJ Neuropathol Exp Neurol · November 1986
The intermediate filament, glial fibrillary acidic protein (GFAP) has proven to be an important glial marker in diagnostic neuropathology. We report the histochemical application of three monoclonal antibodies (Mab) produced in this laboratory, 1B4, 2E1, a ...
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Journal ArticleCancer · May 15, 1986
The authors report three patients who developed fatal respiratory failure after limited or unilateral thoracic radiation therapy for neoplasms. The respiratory failure was characteristic of the adult respiratory distress syndrome (ARDS) with refractory hyp ...
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Journal ArticleArch Pathol Lab Med · November 1985
Calcification has long been a determinant in the radiologic distinction of a benign pulmonary mass. However, rare examples of calcification without ossification in pulmonary adenocarcinoma and ossification in the bronchial carcinoid have led some investiga ...
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Journal ArticleCancer · August 15, 1985
To characterize the incidence and mortality of the glioblastoma multiforme as it is seen at the primary care level, a retrospective study was done through the Georgia Tumor Registry on 299 patients with histologically confirmed supratentorial glioblastoma ...
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Journal ArticleClin Neuropathol · 1985
Abnormalities of the cerebral cortical pattern have been observed in association with the Chiari Type II malformation and described as polymicrogyria, microgyria, stenogyria or polygyria. In order to characterize and quantify these abnormalities, the sulca ...
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Journal ArticleHistochemistry · 1983
Despite the wealth of literature concerned with muscle fiber biochemical, ultrastructural and physiological characteristics, little information is available regarding the metabolic enzyme activities of alpha-motoneurons. The present study examines the meta ...
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Journal ArticleHistochemistry · 1982
The present study examines the use of photographic densitometry combined with atomic absorption spectrophotometry for the quantitation of enzyme activities (SDH and ATPase) in fresh frozen sections of rat tibialis anterior muscles. The technique eliminates ...
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