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John Howard Sampson

Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine
Neurosurgery

Selected Publications


Utility of Routine Preoperative Urinalysis in the Prevention of Surgical Site Infections.

Journal Article World Neurosurg · December 2023 OBJECTIVE: Preoperative assessment is important for neurosurgical risk stratification, but the level of evidence for individual screening tests is low. In preoperative urinalysis (UA), testing may significantly increase costs and lead to inappropriate anti ... Full text Link to item Cite

CD8+ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D-NKG2DL axis.

Journal Article Nat Cancer · September 2023 The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, ... Full text Link to item Cite

Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma.

Journal Article BioDrugs · July 2023 Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and ... Full text Link to item Cite

Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

Journal Article Neuro Oncol · June 2, 2023 BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with po ... Full text Link to item Cite

Outcomes in Patients with Intact and Resected Brain Metastasis Treated with 5-Fraction Stereotactic Radiosurgery.

Journal Article Adv Radiat Oncol · 2023 PURPOSE: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-S ... Full text Link to item Cite

IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma.

Journal Article Front Immunol · 2023 Chimeric antigen receptor (CAR) T cell therapy in glioblastoma faces many challenges including insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, preclinical studies evaluating CAR T cells in glioblastoma f ... Full text Link to item Cite

Drug testing: translating a novel immunotherapeutic from bench to bedside

Chapter · January 1, 2023 Drug development is a time-consuming and expensive process that often fails to translate new, exciting scientific findings into safe and effective clinical therapies. In this chapter, we outline strategies for preclinical drug testing studies, using as an ... Full text Cite

Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury.

Journal Article Anesth Analg · December 1, 2022 BACKGROUND: Early hypotension after severe traumatic brain injury (sTBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors, commonly norepinephrine and phenylephrine, to suppo ... Full text Link to item Cite

Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.

Journal Article Nat Commun · October 29, 2022 Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly ex ... Full text Link to item Cite

Risk Factors and Neurological Outcomes Associated With Circulatory Shock After Moderate-Severe Traumatic Brain Injury: A TRACK-TBI Study.

Journal Article Neurosurgery · September 1, 2022 BACKGROUND: Extracranial multisystem organ failure is a common sequela of severe traumatic brain injury (TBI). Risk factors for developing circulatory shock and long-term functional outcomes of this patient subset are poorly understood. OBJECTIVE: To ident ... Full text Link to item Cite

Multiepitope supramolecular peptide nanofibers eliciting coordinated humoral and cellular antitumor immune responses.

Journal Article Sci Adv · July 22, 2022 Subunit vaccines inducing antibodies against tumor-specific antigens have yet to be clinically successful. Here, we use a supramolecular α-helical peptide nanofiber approach to design epitope-specific vaccines raising simultaneous B cell, CD8+ T cell, and ... Full text Link to item Cite

Utilization of Brain Tissue Oxygenation Monitoring and Association with Mortality Following Severe Traumatic Brain Injury.

Journal Article Neurocrit Care · April 2022 BACKGROUND: The aim of this study was to describe the utilization patterns of brain tissue oxygen (PbtO2) monitoring following severe traumatic brain injury (TBI) and determine associations with mortality, health care use, and pulmonary toxicity. METHODS: ... Full text Open Access Link to item Cite

Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma.

Journal Article Clin Cancer Res · February 15, 2022 Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highl ... Full text Link to item Cite

Glioblastoma Clinical Trials: Current Landscape and Opportunities for Improvement.

Journal Article Clin Cancer Res · February 15, 2022 Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for N ... Full text Link to item Cite

Association of Vasopressor Choice with Clinical and Functional Outcomes Following Moderate to Severe Traumatic Brain Injury: A TRACK-TBI Study.

Journal Article Neurocrit Care · February 2022 BACKGROUND: Early hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following T ... Full text Link to item Cite

Generation of Tumor Targeted Dendritic Cell Vaccines with Improved Immunogenic and Migratory Phenotype.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2022 Our group has employed methodologies for effective ex vivo generation of dendritic cell (DC) vaccines for patients with primary malignant brain tumors. In order to reliably produce the most potent, most representational vaccinated DC that will engender an ... Full text Cite

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143.

Journal Article Neurooncol Adv · 2022 BACKGROUND: The phase 1 cohorts (1c+1d) of CheckMate 143 (NCT02017717) evaluated the safety/tolerability and efficacy of nivolumab plus radiotherapy (RT) ± temozolomide (TMZ) in newly diagnosed glioblastoma. METHODS: In total, 136 patients were enrolled. I ... Full text Link to item Cite

A phase 1 trial of D2C7-it in combination with an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convectionenhanced delivery for adult patients with recurrent malignant glioma (MG).

Conference JOURNAL OF CLINICAL ONCOLOGY · 2022 Background: D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin comprising an EGFR wild-type and mutant-specific (EGFRvIII) monoclonal antibody (Ab) fragment and a genetically engineered form of the Pseudomonas exotoxin. When injected dir ... Full text Link to item Cite

A phase 0/surgical window-of-opportunity study in progress, evaluating evolocumab in patients with high-grade glioma or glioblastoma

Conference JOURNAL OF CLINICAL ONCOLOGY · 2022 Background: High-grade gliomas (HGGs) are immunologically ‘cold’ tumors. This phenomenon is partly due to reduced expression of major histocompatibility class (MHC) I on the surface of tumor cells, which prevents CD8+ cytotoxic T lymphocyte activity (CTLs) ... Full text Link to item Cite

Utility of Routine Preoperative Urinalysis in the Prevention of Surgical Site Infections.

Journal Article World Neurosurg · December 2023 OBJECTIVE: Preoperative assessment is important for neurosurgical risk stratification, but the level of evidence for individual screening tests is low. In preoperative urinalysis (UA), testing may significantly increase costs and lead to inappropriate anti ... Full text Link to item Cite

CD8+ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D-NKG2DL axis.

Journal Article Nat Cancer · September 2023 The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, ... Full text Link to item Cite

Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma.

Journal Article BioDrugs · July 2023 Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and ... Full text Link to item Cite

Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

Journal Article Neuro Oncol · June 2, 2023 BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with po ... Full text Link to item Cite

Outcomes in Patients with Intact and Resected Brain Metastasis Treated with 5-Fraction Stereotactic Radiosurgery.

Journal Article Adv Radiat Oncol · 2023 PURPOSE: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-S ... Full text Link to item Cite

IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma.

Journal Article Front Immunol · 2023 Chimeric antigen receptor (CAR) T cell therapy in glioblastoma faces many challenges including insufficient CAR T cell abundance and antigen-negative tumor cells evading targeting. Unfortunately, preclinical studies evaluating CAR T cells in glioblastoma f ... Full text Link to item Cite

Drug testing: translating a novel immunotherapeutic from bench to bedside

Chapter · January 1, 2023 Drug development is a time-consuming and expensive process that often fails to translate new, exciting scientific findings into safe and effective clinical therapies. In this chapter, we outline strategies for preclinical drug testing studies, using as an ... Full text Cite

Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury.

Journal Article Anesth Analg · December 1, 2022 BACKGROUND: Early hypotension after severe traumatic brain injury (sTBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors, commonly norepinephrine and phenylephrine, to suppo ... Full text Link to item Cite

Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.

Journal Article Nat Commun · October 29, 2022 Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly ex ... Full text Link to item Cite

Risk Factors and Neurological Outcomes Associated With Circulatory Shock After Moderate-Severe Traumatic Brain Injury: A TRACK-TBI Study.

Journal Article Neurosurgery · September 1, 2022 BACKGROUND: Extracranial multisystem organ failure is a common sequela of severe traumatic brain injury (TBI). Risk factors for developing circulatory shock and long-term functional outcomes of this patient subset are poorly understood. OBJECTIVE: To ident ... Full text Link to item Cite

Multiepitope supramolecular peptide nanofibers eliciting coordinated humoral and cellular antitumor immune responses.

Journal Article Sci Adv · July 22, 2022 Subunit vaccines inducing antibodies against tumor-specific antigens have yet to be clinically successful. Here, we use a supramolecular α-helical peptide nanofiber approach to design epitope-specific vaccines raising simultaneous B cell, CD8+ T cell, and ... Full text Link to item Cite

Utilization of Brain Tissue Oxygenation Monitoring and Association with Mortality Following Severe Traumatic Brain Injury.

Journal Article Neurocrit Care · April 2022 BACKGROUND: The aim of this study was to describe the utilization patterns of brain tissue oxygen (PbtO2) monitoring following severe traumatic brain injury (TBI) and determine associations with mortality, health care use, and pulmonary toxicity. METHODS: ... Full text Open Access Link to item Cite

Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma.

Journal Article Clin Cancer Res · February 15, 2022 Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highl ... Full text Link to item Cite

Glioblastoma Clinical Trials: Current Landscape and Opportunities for Improvement.

Journal Article Clin Cancer Res · February 15, 2022 Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for N ... Full text Link to item Cite

Association of Vasopressor Choice with Clinical and Functional Outcomes Following Moderate to Severe Traumatic Brain Injury: A TRACK-TBI Study.

Journal Article Neurocrit Care · February 2022 BACKGROUND: Early hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following T ... Full text Link to item Cite

Generation of Tumor Targeted Dendritic Cell Vaccines with Improved Immunogenic and Migratory Phenotype.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2022 Our group has employed methodologies for effective ex vivo generation of dendritic cell (DC) vaccines for patients with primary malignant brain tumors. In order to reliably produce the most potent, most representational vaccinated DC that will engender an ... Full text Cite

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143.

Journal Article Neurooncol Adv · 2022 BACKGROUND: The phase 1 cohorts (1c+1d) of CheckMate 143 (NCT02017717) evaluated the safety/tolerability and efficacy of nivolumab plus radiotherapy (RT) ± temozolomide (TMZ) in newly diagnosed glioblastoma. METHODS: In total, 136 patients were enrolled. I ... Full text Link to item Cite

A phase 1 trial of D2C7-it in combination with an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convectionenhanced delivery for adult patients with recurrent malignant glioma (MG).

Conference JOURNAL OF CLINICAL ONCOLOGY · 2022 Background: D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin comprising an EGFR wild-type and mutant-specific (EGFRvIII) monoclonal antibody (Ab) fragment and a genetically engineered form of the Pseudomonas exotoxin. When injected dir ... Full text Link to item Cite

A phase 0/surgical window-of-opportunity study in progress, evaluating evolocumab in patients with high-grade glioma or glioblastoma

Conference JOURNAL OF CLINICAL ONCOLOGY · 2022 Background: High-grade gliomas (HGGs) are immunologically ‘cold’ tumors. This phenomenon is partly due to reduced expression of major histocompatibility class (MHC) I on the surface of tumor cells, which prevents CD8+ cytotoxic T lymphocyte activity (CTLs) ... Full text Link to item Cite

Broad immunophenotyping of the murine brain tumor microenvironment.

Journal Article J Immunol Methods · December 2021 Here we present a 14-color flow cytometry panel for the evaluation of 13 myeloid and lymphoid populations within murine glioblastoma samples. Reagents, processing protocols, and downstream analyses were thoroughly validated and optimized to resolve the fol ... Full text Link to item Cite

CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA

Conference Neuro-Oncology · November 12, 2021 AbstractINTRODUCTIONVaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vac ... Full text Open Access Link to item Cite

For whom the T cells troll? Bispecific T-cell engagers in glioblastoma.

Journal Article J Immunother Cancer · November 2021 Glioblastoma is the the most common primary brain tumor in adults. Onset of disease is followed by a uniformly lethal prognosis and dismal overall survival. While immunotherapies have revolutionized treatment in other difficult-to-treat cancers, these have ... Full text Link to item Cite

Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma.

Journal Article Cancers (Basel) · October 26, 2021 Glioblastoma is an immunologically 'cold' tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While man ... Full text Link to item Cite

Association of Severe Acute Kidney Injury with Mortality and Healthcare Utilization Following Isolated Traumatic Brain Injury.

Journal Article Neurocrit Care · October 2021 BACKGROUND/OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of morbidity, mortality, and disability in the USA. While cardiopulmonary dysfunction can result in poor outcomes following severe TBI, the impact of acute kidney injury (AKI) is poorly ... Full text Open Access Link to item Cite

Association of Early Multiple Organ Dysfunction With Clinical and Functional Outcomes Over the Year Following Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.

Journal Article Crit Care Med · October 1, 2021 OBJECTIVES: Traumatic brain injury is a leading cause of death and disability in the United States. While the impact of early multiple organ dysfunction syndrome has been studied in many critical care paradigms, the clinical impact of early multiple organ ... Full text Link to item Cite

Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma.

Journal Article Clin Cancer Res · July 15, 2021 PURPOSE: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in ... Full text Link to item Cite

A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope.

Journal Article NPJ Vaccines · January 18, 2021 Personalized cancer vaccines targeting neoantigens arising from somatic missense mutations are currently being evaluated for the treatment of various cancers due to their potential to elicit a multivalent, tumor-specific immune response. Several cancers ex ... Full text Open Access Link to item Cite

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Journal Article Nat Commun · January 13, 2021 Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunother ... Full text Open Access Link to item Cite

Temozolomide treatment outcomes and immunotherapy efficacy in brain tumor.

Journal Article J Neurooncol · January 2021 INTRODUCTION: Glioblastoma (GBM) has a survival rate of around 2 years with aggressive current standard of care. While other tumors have responded favorably to trials combining immunotherapy and chemotherapy, GBM remains uniformly deadly with minimal incre ... Full text Link to item Cite

Targeting Immunometabolism in Glioblastoma.

Journal Article Front Oncol · 2021 We have only recently begun to understand how cancer metabolism affects antitumor responses and immunotherapy outcomes. Certain immunometabolic targets have been actively pursued in other tumor types, however, glioblastoma research has been slow to exploit ... Full text Link to item Cite

Outcomes in Patients With 4 to 10 Brain Metastases Treated With Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study.

Journal Article Adv Radiat Oncol · 2021 PURPOSE: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. METHODS AND MATERIALS: Adult patients with 4 to 10 brain metastases ... Full text Link to item Cite

CTIM-21. PEPTIDE VACCINE DIRECTED TO CMV pp65 FOR TREATMENT OF RECURRENT MALIGNANT GLIOMA AND MEDULLOBLASTOMA IN CHILDREN AND YOUNG ADULTS: PRELIMINARY RESULTS OF A PHASE I TRIAL

Conference Neuro-Oncology · November 9, 2020 AbstractINTRODUCTIONThe cytomegalovirus (CMV) antigen, pp65, is ubiquitously expressed in malignant glioma and medulloblastoma but not ... Full text Open Access Link to item Cite

PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma?

Journal Article Clin Cancer Res · October 15, 2020 Glioblastoma (WHO grade IV glioma) is the most common malignant primary brain tumor in adults. Survival has remained largely static for decades, despite significant efforts to develop new effective therapies. Immunotherapy and especially immune checkpoint ... Full text Link to item Cite

Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma.

Journal Article Clin Cancer Res · October 15, 2020 Despite standard of care for glioblastoma, including gross total resection, high-dose radiation, and dose-limited chemotherapy, this tumor remains one of the most aggressive and therapeutically challenging. The relatively small number of patients with this ... Full text Link to item Cite

Checkpoint inhibitor immunotherapy for glioblastoma: current progress, challenges and future outlook.

Journal Article Expert Rev Clin Pharmacol · October 2020 INTRODUCTION: Despite maximal surgical resection and chemoradiation, glioblastoma (GBM) continues to be associated with significant morbidity and mortality. Novel therapeutic strategies are urgently needed. Given success in treating multiple other forms of ... Full text Link to item Cite

Determinants of intraparenchymal infusion distributions: Modeling and analyses of human glioblastoma trials

Journal Article Pharmaceutics · September 1, 2020 Intra‐parenchymal injection and delivery of therapeutic agents have been used in clinical trials for brain cancer and other neurodegenerative diseases. The complexity of transport pathways in tissue makes it difficult to envision therapeutic agent distribu ... Full text Cite

Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial.

Journal Article JAMA Oncol · July 1, 2020 IMPORTANCE: Clinical outcomes for glioblastoma remain poor. Treatment with immune checkpoint blockade has shown benefits in many cancer types. To our knowledge, data from a randomized phase 3 clinical trial evaluating a programmed death-1 (PD-1) inhibitor ... Full text Link to item Cite

Oncolytic virus-derived type I interferon restricts CAR T cell therapy.

Journal Article Nat Commun · June 24, 2020 The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test ... Full text Link to item Cite

Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes.

Journal Article Biomater Sci · June 21, 2020 Several different self-assembling peptide systems that form nanofibers have been investigated as vaccine platforms, but design principles for adjusting the character of the immune responses they raise have yet to be well articulated. Here we compared the i ... Full text Link to item Cite

CAR T cells and checkpoint inhibition for the treatment of glioblastoma.

Journal Article Expert Opin Biol Ther · June 2020 Introduction: Glioblastoma (GBM) is a highly aggressive brain tumor and is one of the most lethal human cancers. Chimeric antigen receptor (CAR) T cell therapy has markedly improved survival in previously incurable disease; however, this vanguard treatment ... Full text Link to item Cite

Current multidisciplinary management of brain metastases.

Journal Article Cancer · April 1, 2020 Brain metastasis (BM), the most common adult brain tumor, develops in 20% to 40% of patients with late-stage cancer and traditionally are associated with a poor prognosis. The management of patients with BM has become increasingly complex because of new an ... Full text Link to item Cite

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.

Journal Article Clin Cancer Res · April 1, 2020 PURPOSE: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblas ... Full text Link to item Cite

First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.

Journal Article J Immunother Cancer · April 2020 BACKGROUND: First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with ... Full text Link to item Cite

Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.

Journal Article J Clin Invest · February 3, 2020 Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, sugg ... Full text Link to item Cite

Brain immunology and immunotherapy in brain tumours.

Journal Article Nat Rev Cancer · January 2020 Gliomas, the most common malignant primary brain tumours, remain universally lethal. Yet, seminal discoveries in the past 5 years have clarified the anatomy, genetics and function of the immune system within the central nervous system (CNS) and altered the ... Full text Link to item Cite

GLP toxicology study of a fully-human T cell redirecting CD3:EGFRvIII binding immunotherapeutic bispecific antibody.

Journal Article PLoS One · 2020 We recently reported the development of a fully-human, CD3-binding bispecific antibody for immunotherapy of malignant glioma. To translate this therapeutic (hEGFRvIII-CD3- bi-scFv) to clinical trials and to help further the translation of other similar CD3 ... Full text Link to item Cite

The Evolving Modern Management of Brain Metastasis.

Journal Article Clin Cancer Res · November 15, 2019 The incidence of brain metastases is increasing as cancer therapies improve and patients live longer, providing new challenges to the multidisciplinary teams that care for these patients. Brain metastatic cancer cells possess unique characteristics that al ... Full text Link to item Cite

The current state of immunotherapy for gliomas: an eye toward the future.

Journal Article J Neurosurg · September 1, 2019 The last decade has seen a crescendo of FDA approvals for immunotherapies against solid tumors, yet glioblastoma remains a prominent holdout. Despite more than 4 decades of work with a wide range of immunotherapeutic modalities targeting glioblastoma, effi ... Full text Link to item Cite

Pharmacokinetic Analysis of a Novel Human EGFRvIII:CD3 Bispecific Antibody in Plasma and Whole Blood Using a High-Resolution Targeted Mass Spectrometry Approach.

Journal Article J Proteome Res · August 2, 2019 Bispecific single chain antibody fragments (bi-scFv) represent an emerging class of biotherapeutics. We recently developed a fully human bi-scFv (EGFRvIII:CD3 bi-scFv) with the goal of redirecting CD3-expressing T cells to recognize and destroy malignant, ... Full text Link to item Cite

Challenges to curing primary brain tumours.

Journal Article Nat Rev Clin Oncol · August 2019 Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properti ... Full text Link to item Cite

Brain Tumor Microenvironment and Host State: Implications for Immunotherapy.

Journal Article Clin Cancer Res · July 15, 2019 Glioblastoma (GBM) is a highly lethal brain tumor with poor responses to immunotherapies that have been successful in more immunogenic cancers with less immunosuppressive tumor microenvironments (TME). The GBM TME is uniquely challenging to treat due to tu ... Full text Link to item Cite

MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation.

Journal Article Cancer Res · July 1, 2019 Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic ... Full text Link to item Cite

Safety of nivolumab in combination with dendritic cell vaccines in recurrent high-grade glioma.

Conference Journal of Clinical Oncology · May 20, 2019 e13526 Background: Recurrence of high-grade glioma (HGG) (WHO grade III-IV) is a nearly universal phenomenon and necessitates the development of new therapeutic modalities. Two possible immunotherapeutic modalities are checkpoint ... Full text Cite

Oncolytic polio/rhinovirus recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG): Experience with retreatment of survivors from the phase I trial.

Conference Journal of Clinical Oncology · May 20, 2019 2060 Background: We completed a study evaluating a single intratumoral delivery of PVSRIPO in recurrent WHO grade IV MG patients (N Engl J Med. 2018 Jul 12;379(2):150-161). Some patients who originally benefitted from the infusion of PVSRIPO demonstrated ... Full text Link to item Cite

MDNA55: A locally administered IL4 guided toxin as a targeted treatment for recurrent glioblastoma.

Conference Journal of Clinical Oncology · May 20, 2019 2039 Background: IL4 receptor (IL4R) is frequently and intensely expressed on a variety of human cancers and is associated with poor survival outcomes. Determining the role of the IL4R biomarker in glioblastoma (GBM) will be impo ... Full text Link to item Cite

Effective effectors: How T cells access and infiltrate the central nervous system.

Journal Article Pharmacol Ther · May 2019 Several Phase II and III clinical trials have demonstrated that immunotherapy can induce objective responses in otherwise refractory malignancies in tumors outside the central nervous system. In large part, effector T cells mediate much of the antitumor ef ... Full text Link to item Cite

Immunotherapy for Glioblastoma: Adoptive T-cell Strategies.

Journal Article Clin Cancer Res · April 1, 2019 Glioblastoma (GBM) is a devastating disease with an extremely poor prognosis. Immunotherapy via adoptive cell transfer (ACT), especially with T cells engineered to express chimeric antigen receptors (CAR), represents a particularly promising approach. Desp ... Full text Link to item Cite

Single-institution retrospective review of patients with recurrent glioblastoma treated with bevacizumab in clinical practice.

Journal Article Health Sci Rep · April 2019 BACKGROUND AND AIMS: This retrospective review of patients with recurrent glioblastoma treated at the Preston Robert Tisch Brain Tumor Center investigated treatment patterns, survival, and safety with bevacizumab in a real-world setting. METHODS: Adult pat ... Full text Link to item Cite

The effect of adoptive transfer of ex vivo activated T cells on the efficacy and tumor penetrance of intravenously-administered CD3-engaging bispecific antibody.

Conference Journal of Clinical Oncology · March 10, 2019 30 Background: Activated T cells are known to traffic throughout the body including past the blood-brain barrier where they perform routine immune surveillance. Whether activated T cells can be used to enhance the efficacy and de ... Full text Cite

Author Correction: Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.

Journal Article Nat Med · March 2019 In the version of this article originally published, the figure callout in this sentence was incorrect: "Furthermore, in S1P1-KI mice themselves, whereas PD-1 blockade was ineffectual as monotherapy, the effects of 4-1BB agonism and checkpoint blockade pro ... Full text Link to item Cite

Preventing Lck Activation in CAR T Cells Confers Treg Resistance but Requires 4-1BB Signaling for Them to Persist and Treat Solid Tumors in Nonlymphodepleted Hosts.

Journal Article Clin Cancer Res · January 1, 2019 PURPOSE: Chimeric antigen receptor (CAR) T cells have shown promise against solid tumors, but their efficacy has been limited, due in part, to immunosuppression by CD4+FoxP3+ regulatory T cells (Tregs). Although lymphodepletion is commonly used to deplete ... Full text Link to item Cite

Institutional Review of Mortality in 5434 Consecutive Neurosurgery Patients: Are We Improving?

Journal Article Neurosurgery · December 1, 2018 BACKGROUND: Despite increasing emphasis on quality improvement in neurosurgery, few studies have evaluated the impact of quality initiatives on health-assessment metrics including risk of mortality (ROM), severity of illness (SOI), case mix index (CMI), an ... Full text Link to item Cite

Hyaluronic acid based low viscosity hydrogel as a novel carrier for Convection Enhanced Delivery of CAR T cells.

Journal Article J Clin Neurosci · October 2018 Convection Enhanced Delivery (CED) infuses therapeutic agents directly into the intracranial area continuously under pressure. The convection improves the distribution of therapeutics such as those aimed at brain tumors. Although CED successfully delivers ... Full text Link to item Cite

Understanding biological activity, tumor response and pseudoprogression in a phase-IIb study of MDNA55 in adults with recurrent or progressive glioblastoma (GB)

Conference Annals of Oncology · October 1, 2018 5581 Background MDNA55, a novel Interleukin-4 empowered cytokine fused to Pseudomonas exotoxin, binds to IL-4 receptor (IL-4R) overexpressed by GB and immunosuppressive cells of the tumor microenvironment. Understanding biological effects of MDNA55 and def ... Full text Link to item Cite

Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.

Journal Article Nat Med · September 2018 T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment- ... Full text Link to item Cite

A Rationally Designed Fully Human EGFRvIII:CD3-Targeted Bispecific Antibody Redirects Human T Cells to Treat Patient-derived Intracerebral Malignant Glioma.

Journal Article Clin Cancer Res · August 1, 2018 Purpose: Conventional therapy for malignant glioma fails to specifically target tumor cells. In contrast, substantial evidence indicates that if appropriately redirected, T cells can precisely eradicate tumors. Here we report the rational development of a ... Full text Link to item Cite

A simple and enzyme-free method for processing infiltrating lymphocytes from small mouse tumors for ELISpot analysis.

Journal Article J Immunol Methods · August 2018 The ELISpot assay prevails as one of the most sensitive and meaningful assays for the detection of antigen-specific, effector immune responses. Acquisition of cellular analyte for ELISpot analysis is typically not problematic when derived from tissues enri ... Full text Link to item Cite

Recurrent Glioblastoma Treated with Recombinant Poliovirus.

Journal Article N Engl J Med · July 12, 2018 BACKGROUND: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating ... Full text Link to item Cite

Introduction. Update on adult neuro-oncology.

Journal Article Neurosurg Focus · June 2018 Full text Link to item Cite

Overview of Vaccine Strategies Against Epidermal Growth Factor Receptor in Brain Tumors

Chapter · April 24, 2018 Patients with glioblastoma (GBM) have a dismal prognosis despite the most aggressive multimodal regimen affording a median survival of barely 15 months. Thus, the field is in desperate need of therapies that specifically and safely target these tumors. Arm ... Full text Cite

Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143.

Journal Article Neuro Oncol · April 9, 2018 BACKGROUND: Immunotherapies have demonstrated efficacy across a diverse set of tumors supporting further evaluation in glioblastoma. The objective of this study was to evaluate the safety/tolerability and describe immune-mediated effects of nivolumab ± ipi ... Full text Link to item Cite

Dendritic Cells Enhance Polyfunctionality of Adoptively Transferred T Cells That Target Cytomegalovirus in Glioblastoma.

Journal Article Cancer Res · January 1, 2018 Median survival for glioblastoma (GBM) remains <15 months. Human cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recen ... Full text Link to item Cite

Temozolomide lymphodepletion enhances CAR abundance and correlates with antitumor efficacy against established glioblastoma.

Journal Article Oncoimmunology · 2018 Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is an effective immunotherapy for B-cell malignancies but has failed in some solid tumors clinically. Intracerebral tumors may pose challenges that are even more significant. In orde ... Full text Open Access Link to item Cite

CD27 stimulation unveils the efficacy of linked class I/II peptide vaccines in poorly immunogenic tumors by orchestrating a coordinated CD4/CD8 T cell response.

Journal Article Oncoimmunology · 2018 Despite their promise, tumor-specific peptide vaccines have limited efficacy. CD27 is a costimulatory molecule expressed on CD4+ and CD8+ T cells that is important in immune activation. Here we determine if a novel CD27 agonist antibody (αhCD27) can enhanc ... Full text Link to item Cite

Complications after glioma surgery

Chapter · January 1, 2018 To achieve optimal patient outcomes in brain tumor surgery, it is critical to know how to identify, manage and prevent common complications. From specific to broad, complications can be categorized as local, regional, or systemic. Local complications depen ... Full text Cite

Abstract CN02-02: Immunotherapy for central nervous system cancers

Conference Molecular Cancer Therapeutics · January 1, 2018 AbstractMalignant primary brain tumors are the most frequent cause of cancer death in children and young adults and account for more deaths than cancer of the kidney or melanoma. Despite hundreds of clinical ... Full text Cite

A Supramolecular Vaccine Platform Based on α-Helical Peptide Nanofibers.

Journal Article ACS Biomater Sci Eng · December 11, 2017 A supramolecular peptide vaccine system was designed in which epitope-bearing peptides self-assemble into elongated nanofibers composed almost entirely of alpha-helical structure. The nanofibers were readily internalized by antigen presenting cells and pro ... Full text Link to item Cite

Obituary. Robert H. Wilkins, MD, 1934-2017.

Journal Article Journal of neurosurgery · December 2017 Full text Cite

Chemokines as adjuvants for immunotherapy: implications for immune activation with CCL3.

Journal Article Expert Rev Clin Immunol · November 2017 Immunotherapy embodies any approach that manipulates the immune system for therapeutic benefit. In this regard, various clinical trials have employed direct vaccination with patient-specific dendritic cells or adoptive T cell therapy to target highly aggre ... Full text Link to item Cite

Pre-operative stereotactic radiosurgery treatment is preferred to post-operative treatment for smaller solitary brain metastases

Journal Article Chinese Neurosurgical Journal · October 3, 2017 Background: While the optimal combination of whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) and surgical resection in the treatment of brain metastases, is controversial, the addition of SRS to surgical resction of solitary metastasis may ... Full text Cite

Biopsy of enlarging lesions after stereotactic radiosurgery for brain metastases frequently reveals radiation necrosis.

Journal Article Neuro Oncol · October 1, 2017 BACKGROUND: Stereotactic radiosurgery (SRS) offers excellent local control for brain metastases (BM) with low rates of toxicity. Radiation necrosis (RN) may occur after treatment and is challenging to distinguish from local recurrence (LR). We evaluated en ... Full text Link to item Cite

Accuracy of Novel Computed Tomography-Guided Frameless Stereotactic Drilling and Catheter System in Human Cadavers.

Journal Article World Neurosurg · October 2017 OBJECTIVE: To evaluate accuracy of a computed tomography (CT)-guided frameless stereotactic drilling and catheter system. METHODS: A prospective, single-arm study was performed using human cadaver heads to evaluate placement accuracy of a novel, flexible i ... Full text Link to item Cite

Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial.

Journal Article Lancet Oncol · October 2017 BACKGROUND: Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the additio ... Full text Link to item Cite

Immunotherapy for Brain Tumors.

Journal Article J Clin Oncol · July 20, 2017 Glioblastoma (GBM) is the most lethal form of brain tumor and remains a large, unmet medical need. This review focuses on recent advances in the neurosciences that converge with the broader field of immuno-oncology. Recent findings in neuroanatomy provide ... Full text Link to item Cite

Immunomodulation for glioblastoma.

Journal Article Curr Opin Neurol · June 2017 PURPOSE OF REVIEW: Immunotherapy has emerged as a cornerstone of modern oncology with regulatory approvals for a variety of immunotherapeutics being achieved for a spectrum of cancer indications. Nonetheless the role of these approaches for patients with g ... Full text Link to item Cite

Vaccine-based immunotherapeutic approaches to gliomas and beyond.

Journal Article Nat Rev Neurol · June 2017 Astrocytic and oligodendroglial gliomas are intrinsic brain tumours characterized by infiltrative growth and resistance to classic cancer therapies, which renders them inevitably lethal. Glioblastoma, the most common type of glioma, also exhibits neoangiog ... Full text Link to item Cite

Dose finding study of the intratumoral administration of the oncolytic polio/rhinovirus recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG).

Conference Journal of Clinical Oncology · May 20, 2017 e13533 Background: The live attenuated oral poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal c ... Full text Link to item Cite

Phase 1 single-center, dose escalation study of D2C7-IT administered intratumorally via convection-enhanced delivery for adult patients with recurrent malignant glioma.

Conference Journal of Clinical Oncology · May 20, 2017 e13532 Background: D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin consisting of EGFR-wt and EGFRvIII monoclonal antibodies with a genetically engineered Pseudomonas exotoxin, PE-38KDEL. The primary objectiv ... Full text Link to item Cite

Tumor stem cell RNA-leaded dedritic cell vaccine for recurrent glioblastoma: a phase 1 trail.

Conference Neurology · April 27, 2017 Objective: To evaluate the feasibility and safety of administering brain tumor stem cell (BTSC) mRNA-loaded dendritic cells (DC) to patients with recurrent GBM. Background: BTSC CD133+ contribute to GBM propagation and are associated with chemo-radiation ... Link to item Cite

Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination.

Journal Article Clin Cancer Res · April 15, 2017 Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can e ... Full text Link to item Cite

Prospect of rindopepimut in the treatment of glioblastoma.

Journal Article Expert Opin Biol Ther · April 2017 Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain - glioblastoma (GBM). Areas covered: ... Full text Link to item Cite

Launching Effectiveness Research to Guide Practice in Neurosurgery: A National Institute Neurological Disorders and Stroke Workshop Report.

Journal Article Neurosurgery · April 1, 2017 This workshop addressed challenges of clinical research in neurosurgery. Randomized controlled clinical trials (RCTs) have high internal validity, but often insufficiently generalize to real-world practice. Observational studies are inclusive but often lac ... Full text Link to item Cite

Immunotoxin Therapy for Brain Tumors

Chapter · March 2, 2017 Despite a multimodal approach involving surgery, radiotherapy, and chemotherapy, the median survival for malignant brain tumor patients is limited to 15-19. months. To improve glioblastoma patient survival, novel therapies targeting the heterogeneous tumor ... Full text Cite

Checkpoint Blockade Immunotherapy for Glioblastoma: Progress and Challenges

Chapter · March 2, 2017 Conventional therapy for glioblastoma (GBM) fails to specifically target and eliminate tumor cells, resulting in nonspecific toxicity that limits therapeutic efficacy. In contrast, immunotherapy utilizes the immune system to eradicate tumor cells with exqu ... Full text Cite

An Introduction to Immunotherapy in the Treatment of Brain Tumors

Chapter · March 2, 2017 Malignant brain tumors represent an aggressive disease entity. The lack of specificity of standard therapy damages nonmalignant tissue. These off-target effects result in both short-term and long-term complications, which limit quality of life. Exciting op ... Full text Cite

Translational Immunotherapy of Brain Tumors

Book · March 2, 2017 Translational Immunotherapy of Brain Tumors gives researchers and practitioners an up-to-date and comprehensive overview of the field. Chapters include adoptive immunotherapy, immunosuppression, CAR therapy of brain tumors, and dendritic cell therapy for b ... Cite

The clinical and financial impact of a pediatric surgical neuro-oncology clinical trial.

Journal Article J Neurooncol · March 2017 Pediatric surgical trials are rare and the impact of such trials on the institutions in which they are conducted is unknown. The purpose of this study was to analyze the clinical and financial impact of The Re-MATCH trial, a Phase I clinical trial requirin ... Full text Link to item Cite

The Safety of available immunotherapy for the treatment of glioblastoma.

Journal Article Expert Opin Drug Saf · March 2017 Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors w ... Full text Link to item Cite

Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles.

Journal Article Oncoimmunology · 2017 While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanolipos ... Full text Link to item Cite

Advances and challenges: dendritic cell vaccination strategies for glioblastoma.

Journal Article Expert Rev Vaccines · January 2017 Glioblastoma is the most common primary brain tumor in adults and prognosis remains poor with a median survival of approximately 15-17 months. This review provides an overview of recent advances in the field of glioblastoma immunotherapy. Areas covered: Re ... Full text Link to item Cite

Single fraction stereotactic radiosurgery for multiple brain metastases.

Journal Article Adv Radiat Oncol · 2017 INTRODUCTION: Due to the neurocognitive side effects of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) is being used with increasing frequency. The use of SRS is expanding for patients with multiple (>4) brain metastases (BM). This s ... Full text Open Access Link to item Cite

The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial.

Journal Article Front Immunol · 2017 INTRODUCTION: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these fin ... Full text Link to item Cite

Immunotherapy Gone Viral: Bortezomib and oHSV Enhance Antitumor NK-Cell Activity.

Journal Article Clin Cancer Res · November 1, 2016 Oncolytic viruses, proteasome inhibitors, and natural killer (NK)-cell immunotherapy have all been studied extensively as monotherapies but have never been evaluated in combination. Synergetic treatment of oncolytic virus-infected glioblastomas with a prot ... Full text Link to item Cite

Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

Journal Article Cancer Res · September 1, 2016 Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genet ... Full text Link to item Cite

369 Chimeric Antigen Receptors Deficient in Lck Signaling Require 4-1BB Costimulation to Expand in Vivo, Resist Regulatory T-Cell Suppression, and Treat Solid Tumors in Immune-Intact Hosts.

Journal Article Neurosurgery · August 2016 INTRODUCTION: Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is an effective immunotherapy for hematological cancers but requires a rethinking for clinical efficacy against solid tumors, where CARs have largely failed. Lymphodepl ... Full text Link to item Cite

Delivering therapy to target: improving the odds for successful drug development.

Journal Article Ther Deliv · July 2016 The direct delivery of drugs and other agents into tissue (in contrast to systemic administration) has been used in clinical trials for brain cancer, neurodegenerative diseases and peripheral tumors. However, continuing evidence suggests that clinical effi ... Full text Link to item Cite

Emerging immunotherapies for glioblastoma.

Journal Article Expert Opin Emerg Drugs · June 2016 INTRODUCTION: Immunotherapy for brain cancer has evolved dramatically over the past decade, owed in part to our improved understanding of how the immune system interacts with tumors residing within the central nervous system (CNS). Glioblastoma (GBM), the ... Full text Link to item Cite

Patient survival on the dose escalation phase of the Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG) clinical trial compared to historical controls.

Conference Journal of Clinical Oncology · May 20, 2016 Background: The live attenuated oral (SABIN) serotype 1 poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion mo ... Full text Link to item Cite

Phase I trial of combination of antitumor immunotherapy targeted against cytomegalovirus (CMV) plus regulatory T-cell inhibition in patients with newly-diagnosed glioblastoma multiforme (GBM).

Conference Journal of Clinical Oncology · May 20, 2016 ackground: The inherent biologic specificity of immunotherapy offers the prospect of targeting neoplastic cells more precisely. Dendritic cells (DCs) are endowed with an extraordinary ability to activate CD4+ and CD8+ T-cells, and DCs loaded with antigens ... Full text Link to item Cite

The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.

Journal Article J Alzheimers Dis · April 15, 2016 BACKGROUND: Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)-associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ). OBJECTIVE: We asked whether isoflurane and propofol have diffe ... Full text Open Access Link to item Cite

Genetics of glioma

Chapter · March 31, 2016 Provides a summary of glioma biology, genetics and management, based on the world-leading Duke University Preston Robert Tisch Brain Tumor Center program. ... Link to item Cite

Immunotherapy for gliomas

Chapter · March 31, 2016 Full text Cite

Radiation therapy for gliomas

Chapter · March 31, 2016 Full text Cite

The Duke glioma handbook: Pathology, diagnosis, and management

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 ... Full text Cite

Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

Journal Article Clin Cancer Res · February 1, 2016 PURPOSE: Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. ... Full text Link to item Cite

Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy.

Journal Article Cancer Immunol Immunother · February 2016 Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator ... Full text Link to item Cite

Preconditioning Vaccine Sites for mRNA-Transfected Dendritic Cell Therapy and Antitumor Efficacy.

Chapter · 2016 Messenger RNA (mRNA)-transfected dendritic cell (DC) vaccines have been shown to be a powerful modality for eliciting antitumor immune responses in mice and humans; however, their application has not been fully optimized since many of the factors that cont ... Full text Link to item Cite

Immunotherapy for high-grade gliomas

Chapter · January 1, 2016 Malignant gliomas are the most common primary brain tumor in adults, with an incidence of five cases per 100,000 persons per year. Grade IV glioblastoma is the most aggressive form and prognosis remains poor despite the current gold-standard first-line tre ... Full text Cite

Vaccination strategies for neuro-oncology.

Journal Article Neuro Oncol · November 2015 Vaccination against cancer-associated antigens has long held the promise of inducting potent antitumor immunity, targeted cytotoxicity while sparing normal tissues, and long-lasting immunologic memory that can provide surveillance against tumor recurrence. ... Full text Link to item Cite

Immunotherapy response assessment in neuro-oncology: a report of the RANO working group.

Journal Article Lancet Oncol · November 2015 Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed respons ... Full text Link to item Cite

Patient validation of retrospective data.

Journal Article J Neurosurg · October 2015 Full text Link to item Cite

Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma.

Journal Article J Neurooncol · October 2015 Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies ... Full text Link to item Cite

Prospects of immune checkpoint modulators in the treatment of glioblastoma.

Journal Article Nat Rev Neurol · September 2015 Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment—maximal safe resection and combination of radiotherapy with temozolomide chemotherapy—the median overall survival ti ... Full text Link to item Cite

Peptide vaccines for the treatment of glioblastoma.

Journal Article J Neurooncol · July 2015 Glioblastoma multiforme (GBM) is an extremely malignant brain tumor for which current therapies do little to remedy. Despite aggressive treatment with surgery, radiation therapy, and chemotherapy, tumors inevitably recur as a direct consequence of the infi ... Full text Link to item Cite

A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study.

Journal Article Neuro Oncol · June 2015 BACKGROUND: The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhol ... Full text Link to item Cite

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.

Journal Article J Neurochem · June 2015 The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characte ... Full text Link to item Cite

Are BiTEs the "missing link" in cancer therapy?

Journal Article Oncoimmunology · June 2015 Conventional treatment for cancer routinely includes surgical resection and some combination of chemotherapy and radiation. These approaches are frequently accompanied by unintended and highly toxic collateral damage to healthy tissues, which are offset by ... Full text Link to item Cite

Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.

Journal Article Cancer Immunol Res · April 2015 Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimul ... Full text Link to item Cite

Increased proportion of FoxP3+ regulatory T cells in tumor infiltrating lymphocytes is associated with tumor recurrence and reduced survival in patients with glioblastoma.

Journal Article Cancer Immunol Immunother · April 2015 Glioblastoma multiforme (GBM) is an aggressive malignancy associated with profound host immunosuppression mediated in part by FoxP3 expressing regulatory CD4+ T lymphocytes (Tregs) that down-regulate anti-tumor immunity. In order to assess whether FoxP3 wa ... Full text Link to item Cite

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

Journal Article Nature · March 19, 2015 After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vacci ... Full text Open Access Link to item Cite

Novel role of hematopoietic stem cells in immunologic rejection of malignant gliomas.

Journal Article Oncoimmunology · March 2015 Adoptive cellular therapy (ACT) after lymphodepletive conditioning can induce dramatic clinical responses, but this approach has been largely limited to melanoma due to a lack of reliable methods for expanding tumor-specific lymphocytes from the majority o ... Full text Link to item Cite

miR-23a blockade enhances adoptive T cell transfer therapy by preserving immune-competence in the tumor microenvironment.

Journal Article Oncoimmunology · March 2015 In adoptive T cell transfer therapy (ACT), the antitumor efficacy of cytotoxic CD8+ T lymphocytes (CTLs) has been limited by tumor-induced immunosuppression. We have demonstrated that miR-23a blockade in tumor-specific CTLs conferred resilience to TGFβ-med ... Full text Link to item Cite

Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care.

Journal Article J Vis Exp · February 16, 2015 Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo to express chimeric antigen receptors specific for glioma antigens (CAR T cells). The expansion and fu ... Full text Link to item Cite

Enhancing dendritic cell-based vaccination for highly aggressive glioblastoma.

Journal Article Expert Opin Biol Ther · January 2015 INTRODUCTION: Patients with primary glioblastoma (GBM) have a dismal prognosis despite standard therapy, which can induce potentially deleterious side effects. Arming the immune system is an alternative therapeutic approach, as its cellular effectors and i ... Full text Link to item Cite

Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial.

Journal Article Int J Radiat Oncol Biol Phys · January 1, 2015 PURPOSE: To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. METHODS AND MATERIALS: Adult patients with 1 to 3 brain metastases less than 4 cm ... Full text Link to item Cite

Immunotherapy for malignant glioma.

Journal Article Surg Neurol Int · 2015 Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery ... Full text Link to item Cite

Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression.

Journal Article J Clin Invest · December 2014 CD8(+) cytotoxic T lymphocytes (CTLs) have potent antitumor activity and therefore are leading candidates for use in tumor immunotherapy. The application of CTLs for clinical use has been limited by the susceptibility of ex vivo-expanded CTLs to become dys ... Full text Link to item Cite

Immunotherapy for primary brain tumors: no longer a matter of privilege.

Journal Article Clin Cancer Res · November 15, 2014 Immunotherapy for cancer continues to gain both momentum and legitimacy as a rational mode of therapy and a vital treatment component in the emerging era of personalized medicine. Gliomas, and their most malignant form, glioblastoma, remain as a particular ... Full text Link to item Cite

Oncolytic polio virotherapy of cancer.

Journal Article Cancer · November 1, 2014 Featured Publication Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct ... Full text Link to item Cite

Immunotherapy advances for glioblastoma.

Journal Article Neuro Oncol · November 2014 Survival for patients with glioblastoma, the most common high-grade primary CNS tumor, remains poor despite multiple therapeutic interventions including intensifying cytotoxic therapy, targeting dysregulated cell signaling pathways, and blocking angiogenes ... Full text Link to item Cite

Standard of care and future pharmacological treatment options for malignant glioma: an urgent need for screening and identification of novel tumor-specific antigens.

Journal Article Expert Opin Pharmacother · October 2014 Featured Publication INTRODUCTION: Malignant gliomas (MGs) represent the most common primary brain tumors in adults, the most deadly of which is grade IV glioblastoma. Patients with glioblastoma undergoing current standard-of-care therapy have a median survival of 12 - 15 mont ... Full text Link to item Cite

Recurrent malignant gliomas.

Journal Article Semin Radiat Oncol · October 2014 In almost all patients, malignant glioma recurs following initial treatment with maximal safe resection, conformal radiotherapy, and temozolomide. This review describes the many options for treatment of recurrent malignant gliomas, including reoperation, a ... Full text Link to item Cite

Epidermal growth factor receptor and variant III targeted immunotherapy.

Journal Article Neuro Oncol · October 2014 Immunotherapeutic approaches to cancer have shown remarkable promise. A critical barrier to successfully executing such immune-mediated interventions is the selection of safe yet immunogenic targets. As patient deaths have occurred when tumor-associated an ... Full text Link to item Cite

A novel, reproducible, and objective method for volumetric magnetic resonance imaging assessment of enhancing glioblastoma.

Journal Article J Neurosurg · September 2014 Featured Publication OBJECT: Robust methodology that allows objective, automated, and observer-independent measurements of brain tumor volume, especially after resection, is lacking. Thus, determination of tumor response and progression in neurooncology is unreliable. The obje ... Full text Link to item Cite

Worse outcomes for patients undergoing brain tumor and cerebrovascular procedures following the ACGME resident duty-hour restrictions.

Journal Article J Neurosurg · August 2014 Featured Publication OBJECT: On July 1, 2003, the Accreditation Council for Graduate Medical Education (ACGME) implemented duty-hour restrictions for resident physicians due to concerns for patient and resident safety. Though duty-hour restrictions have increased resident qual ... Full text Link to item Cite

Antibody-based immunotherapy for malignant glioma.

Journal Article Semin Oncol · August 2014 Conventional therapy for malignant glioma (MG) fails to specifically eliminate tumor cells, resulting in toxicity that limits therapeutic efficacy. In contrast, antibody-based immunotherapy uses the immune system to eliminate tumor cells with exquisite spe ... Full text Link to item Cite

Idh1 mutations as a immunotherapeutic target for brain tumors.

Journal Article Neuro Oncol · July 2014 Immunotherapy promises an exquisitely precise therapeutic approach, and substantial evidence suggests that activated T cells can eradicate large tumors, even within the "immunologically privileged" brain. EGFRvIII and isocitrate dehydrogenase 1 (IDH1) muta ... Full text Link to item Cite

Oncolytic polio/rhinovirus recombinant (pvsripo) in recurrent glioblastoma (gbm): first phase I clinical trial evaluating the intratumoral administration.

Journal Article Neuro Oncol · July 2014 PVSRIPO is the live attenuated, oral (SABIN) serotype 1 poliovirus vaccine containing a heterologous internal ribosomal entry site stemming from human rhinovirus type 2. PVSRIPO recognizes nectin-like molecule-5, an oncofetal cell adhesion molecule and tum ... Full text Link to item Cite

Recognition and killing of autologous, primary glioblastoma tumor cells by human cytomegalovirus pp65-specific cytotoxic T cells.

Journal Article Clin Cancer Res · May 15, 2014 Featured Publication PURPOSE: Despite aggressive conventional therapy, glioblastoma (GBM) remains uniformly lethal. Immunotherapy, in which the immune system is harnessed to specifically attack malignant cells, offers a treatment option with less toxicity. The expression of cy ... Full text Link to item Cite

Response.

Journal Article J Neurosurg · March 2014 Link to item Cite

Editorial: the impact of PhD training.

Journal Article J Neurosurg · March 2014 Full text Link to item Cite

EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.

Journal Article Clin Cancer Res · February 15, 2014 Featured Publication PURPOSE: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to ... Full text Link to item Cite

SEER insights.

Journal Article J Neurosurg · February 2014 Full text Link to item Cite

EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

Journal Article PLoS One · 2014 Featured Publication Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal bra ... Full text Open Access Link to item Cite

Rindopepimut: a promising immunotherapeutic for the treatment of glioblastoma multiforme.

Journal Article Immunotherapy · 2014 Featured Publication Glioblastoma multiforme (GBM) is the most common and aggressive glial cell-derived primary tumor. Current standard of care for patients with GBM includes maximal tumor resection plus adjuvant radiotherapy and temozolomide chemotherapy, increasing median ov ... Full text Link to item Cite

Immunological targeting of cytomegalovirus for glioblastoma therapy.

Journal Article Oncoimmunology · 2014 Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are c ... Full text Link to item Cite

Leveraging chemotherapy-induced lymphopenia to potentiate cancer immunotherapy.

Journal Article Oncoimmunology · 2014 First-line chemotherapy to combat primary malignant brain cancer is often accompanied by lymphopenic immunologic deficiency. Although counterintuitive, chemotherapy-induced lymphopenia can provide excellent host conditioning that may actually be leveraged ... Full text Link to item Cite

Chimeric antigen receptor engineered T cells can eliminate brain tumors and initiate long-term protection against recurrence.

Journal Article Oncoimmunology · 2014 CAR therapy has shown promise in treating cancer, but at the cost of unexpected toxicity against normal tissues, not predicted by preclinical testing. We are working to generate more physiologically relevant models for preclinical CAR toxicity testing, and ... Full text Link to item Cite

Low-dose whole brain radiotherapy combined with radiosurgery for primary CNS lymphoma achieving partial response to induction methotrexate-based chemotherapy.

Journal Article J Radiosurg SBRT · 2014 PURPOSE: For patients with primary CNS lymphoma who achieve complete response (CR) after induction methotrexate-based chemotherapy with rituximab, low-dose whole brain radiation therapy (LD-WBRT) appears effective and is well tolerated. For patients who re ... Link to item Cite

Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma.

Journal Article J Clin Neurosci · January 2014 Featured Publication Chimeric antigen receptors (CAR)-transduced T cells hold great promise in the treatment of malignant disease. Here, we demonstrate that intracerebral injection with a human, epidermal growth factor receptor variant III (EGFRvIII)-specific, third generation ... Full text Link to item Cite

Regulatory T cells are redirected to kill glioblastoma by an EGFRvIII-targeted bispecific antibody.

Journal Article Oncoimmunology · December 1, 2013 Regulatory T cells (Tregs) play a central role in in tumor escape from immunosurveillance. We report that a bispecific T-cell engager (BiTE) targeting a mutated form of the epidermal growth factor receptor, i.e., EGFRvIII, potently redirects Tregs to kill ... Full text Link to item Cite

Regulatory T cells are redirected to kill glioblastoma by an EGFRviii-targeted bispecific antibody

Journal Article OncoImmunology · December 1, 2013 Regulatory T cells (Tregs) play a central role in in tumor escape from immunosurveillance. We report that a bispecific T-cell engager (BiTE) targeting a mutated form of the epidermal growth factor receptor, i.e., EGFRvIII, potently redirects Tregs to kill ... Full text Cite

A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model.

Journal Article Cancer Immunol Immunother · November 2013 Adoptive cell transfer (ACT) using ex vivo-expanded anti-tumor T cells such as tumor-infiltrated lymphocytes or genetically engineered T cells potently eradicates established tumors. However, these two approaches possess obvious limitations. Therefore, we ... Full text Link to item Cite

Complete response to steroids in dural inflammatory pseudotumor associated with Still's disease.

Journal Article J Clin Neurosci · October 2013 We report a unique case of a dural-based inflammatory pseudotumor (IPT) arising in the left cavernous sinus of a patient with a history of juvenile Still's disease. The patient presented with hemi-facial paresthesias, dull, constant headaches, and transien ... Full text Link to item Cite

Rational design and generation of recombinant control reagents for bispecific antibodies through CDR mutagenesis.

Journal Article J Immunol Methods · September 30, 2013 Developments in the field of bispecific antibodies have progressed rapidly in recent years, particularly in their potential role for the treatment of malignant disease. However, manufacturing stable molecules has proven to be costly and time-consuming, whi ... Full text Link to item Cite

Human regulatory T cells kill tumor cells through granzyme-dependent cytotoxicity upon retargeting with a bispecific antibody.

Journal Article Cancer Immunol Res · September 2013 A major mechanism by which human regulatory T cells (T(regs)) have been shown to suppress and kill autologous immune cells is through the granzyme-perforin pathway. However, it is unknown whether T(regs) also possess the capacity to kill tumor cells using ... Full text Link to item Cite

Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial.

Journal Article Int J Radiat Oncol Biol Phys · August 1, 2013 PURPOSE: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. METHODS AND MATERIALS: ... Full text Link to item Cite

107 Dose-finding and safety study of an oncolytic polio/rhinovirus recombinant against recurrent glioblastoma.

Journal Article Neurosurgery · August 2013 Current therapies for glioblastoma are limited by ineffective delivery beyond the blood-brain barrier, limited diffusion of regionally-delivered macromolecules, and lack of tumor specificity. Sustained direct intracerebral infusion at slow flow rates [conv ... Full text Link to item Cite

Clinicopathological characteristics and treatment of rhabdoid glioblastoma.

Journal Article J Neurosurg · August 2013 OBJECT: Rhabdoid glioblastoma (GB) is an exceedingly rare tumor in which some of the tumor cells possess rhabdoid features such as eccentric nuclei, abundant eosinophilic cytoplasm, and pseudopapillary formations. These tumors are exceptionally aggressive, ... Full text Link to item Cite

Radiotherapy and radiosurgery for tumors of the central nervous system.

Journal Article Surg Oncol Clin N Am · July 2013 In this article, the application of radiotherapy, alone and in combination with surgery and chemotherapy, in the treatment of metastases to the brain (the most common malignant brain lesion), primary malignant gliomas (the most common malignant primary bra ... Full text Link to item Cite

Antibody, T-cell and dendritic cell immunotherapy for malignant brain tumors.

Journal Article Future Oncol · July 2013 Modest improvement in brain tumor patient survival has been achieved through advances in surgical, adjuvant radiation and chemotherapeutic strategies. However, these traditional approaches have been unsuccessful in permanently controlling these aggressive ... Full text Link to item Cite

An EGFRvIII-targeted bispecific T-cell engager overcomes limitations of the standard of care for glioblastoma.

Journal Article Expert Rev Clin Pharmacol · July 2013 While advanced surgical techniques, radiation therapy and chemotherapeutic regimens provide a tangible benefit for patients with glioblastoma (GBM), the average survival from the time of diagnosis remains less than 15 months. Current therapy for GBM is lim ... Full text Link to item Cite

Melanoma immunotherapy using mature DCs expressing the constitutive proteasome.

Journal Article J Clin Invest · July 2013 BACKGROUND: Many cancers, including melanoma, exclusively express constitutive proteasomes (cPs) and are unable to express immunoproteasomes (iPs). In contrast, mature DCs used for immunotherapy exclusively express iPs. Since proteasomes generate peptides ... Full text Link to item Cite

Contemporary surgical management of vestibular schwannomas: analysis of complications and lessons learned over the past decade.

Journal Article Neurosurgery · June 2013 BACKGROUND: Despite advanced microsurgical techniques, more refined instrumentation, and expert team management, there is still a significant incidence of complications in vestibular schwannoma surgery. OBJECTIVE: To analyze complications from the microsur ... Full text Link to item Cite

Isocitrate dehydrogenase 1: what it means to the neurosurgeon: a review.

Journal Article J Neurosurg · June 2013 Isocitrate dehydrogenase 1 (IDH1) mutations have been discovered to be frequent and highly conserved in secondary glioblastoma multiforme and lower-grade gliomas. Although IDH1 mutations confer a unique genotype that has been associated with a favorable pr ... Full text Link to item Cite

BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide.

Journal Article Cancer Immunol Immunother · June 2013 B lymphocyte stimulator (BLyS) is a cytokine involved in differentiation and survival of follicular B cells along with humoral response potentiation. Lymphopenia is known to precipitate dramatic elevation in serum BLyS; however, the use of this effect to e ... Full text Link to item Cite

An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma.

Journal Article Expert Rev Vaccines · June 2013 Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancer ... Full text Link to item Cite

Current immunotherapeutic targets in gliomas

Journal Article · May 1, 2013 The prospect for high-grade astrocytic tumor patients continues to be dismal, evenwith advances in surgery, radiotherapy, and chemotherapy. There is a need for thedevelopment of novel therapies that would eliminate the heterogeneous and diffuseastrocytic t ... Cite

Therapeutic approaches for HER2-positive brain metastases: circumventing the blood-brain barrier.

Journal Article Cancer Treat Rev · May 2013 We aim to summarize data from studies of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and brain metastasis and to describe novel methods being developed to circumvent the blood-brain b ... Full text Link to item Cite

A novel bispecific antibody recruits T cells to eradicate tumors in the "immunologically privileged" central nervous system.

Journal Article Oncoimmunology · April 1, 2013 Bispecific T-cell engagers (BiTEs) may break multiple barriers that currently limit the use of immunotherapy in glioblastoma patients. We have recently described a novel BiTE specific for a mutated form of the epidermal growth factor receptor, EGFRvIII, th ... Full text Link to item Cite

Rindopepimut: anti-EGFRvIII peptide vaccine, oncolytic.

Journal Article Drugs Future · March 2013 Glioblastoma, the most common primary malignant brain tumor, is among the most difficult cancers to treat. Despite the aggressive standard of care, including surgical removal followed by radiotherapy with concomitant and adjuvant chemotherapy, the often su ... Full text Link to item Cite

Thickness of subcutaneous fat as a risk factor for infection in cervical spine fusion surgery.

Journal Article J Bone Joint Surg Am · February 20, 2013 BACKGROUND: Surgical site infections increase the incidence of morbidity and mortality as well as health-care expenses. The cost of care increases threefold to fourfold as a consequence of surgical site infection after spinal surgery. The aim of the presen ... Full text Link to item Cite

Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma.

Journal Article Proc Natl Acad Sci U S A · January 2, 2013 Bispecific antibodies (bscAbs), particularly those of the bispecific T-cell engager (BiTE) subclass, have been shown to effectively redirect T cells against cancer. Previous efforts to target antigens expressed in both tumors and normal tissues have produc ... Full text Link to item Cite

Subarachnoid hemorrhage trials.

Journal Article J Neurosurg · January 2013 Full text Link to item Cite

Myeloablative temozolomide enhances CD8⁺ T-cell responses to vaccine and is required for efficacy against brain tumors in mice.

Journal Article PLoS One · 2013 Temozolomide (TMZ) is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases. A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be ... Full text Open Access Link to item Cite

Convection enhanced delivery of macromolecules for brain tumors.

Journal Article Curr Drug Discov Technol · December 2012 The blood brain barrier (BBB) poses a significant challenge for drug delivery of macromolecules into the brain. Convection-enhanced delivery (CED) circumvents the BBB through direct intracerebral infusion using a hydrostatic pressure gradient to transfer t ... Full text Link to item Cite

Editorial: Convection-enhanced delivery.

Journal Article J Neurosurg · December 2012 Full text Link to item Cite

Immunotherapy with tumor vaccines for the treatment of malignant gliomas.

Journal Article Curr Drug Discov Technol · December 2012 With an average life expectancy of 14 months, Glioblastoma multiforme (GBM), is the most aggressive primary brain tumor. Our growing understanding of the immune system and its role in oncogenesis has helped develop cancer vaccines as a promising treatment ... Full text Link to item Cite

Regulatory T cells move in when gliomas say "I Do".

Journal Article Clin Cancer Res · November 15, 2012 Indoleamine 2,3-dioxygenase (IDO) is an enzyme with known immunosuppressive and tolerogenic effects in cancer. Mounting evidence has associated IDO expression with the induction of regulatory T cells (Treg) and malignant progression. IDO inhibition may the ... Full text Link to item Cite

Enzyme redesign guided by cancer-derived IDH1 mutations.

Journal Article Nat Chem Biol · November 2012 Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases to homologous residues in the active sites of homoisocitrate dehydrogenases to derive enzymes that cataly ... Full text Link to item Cite

The limitations of imaging response criteria.

Journal Article Lancet Oncol · November 2012 Full text Link to item Cite

Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients.

Journal Article Br J Cancer · October 23, 2012 BACKGROUND: Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among rec ... Full text Open Access Link to item Cite

Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma.

Journal Article J Neurooncol · July 2012 To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of dasatinib, an inhibitor of the Src family kinase proteins, with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, among recurrent malignant glioma pat ... Full text Link to item Cite

Resection and survival.

Journal Article J Neurosurg · June 2012 Full text Link to item Cite

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

Journal Article Technol Cancer Res Treat · June 2012 Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the b ... Full text Link to item Cite

Stereotactic radiosurgery and bevacizumab for recurrent glioblastoma multiforme.

Journal Article J Natl Compr Canc Netw · June 1, 2012 Despite contemporary surgery, image-guided radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) persists or relapses in nearly all patients, and tumors almost always recur locally. Management of recurrent GBM is variable, but approaches include be ... Full text Link to item Cite

The use of motor mapping to aid resection of eloquent gliomas.

Journal Article Neurosurg Clin N Am · April 2012 Surgery remains one of the oldest and still most important forms of treatment for patients with glioma. The advantages of surgical resection for glioma must be balanced with the potential of operative morbidity to surrounding eloquent brain. To that end, a ... Full text Link to item Cite

Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas.

Journal Article Int J Radiat Oncol Biol Phys · April 1, 2012 PURPOSE: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. METHODS AND MATERIA ... Full text Link to item Cite

Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma.

Journal Article J Neurooncol · March 2012 We evaluated the efficacy of carboplatin, irinotecan, and bevacizumab among bevacizumab-naïve, recurrent glioblastoma (GBM) patients in a phase 2, open-label, single arm trial. Forty eligible patients received carboplatin (area under the plasma curve [AUC] ... Full text Link to item Cite

Clinical data simplified.

Journal Article J Neurosurg · February 2012 Full text Link to item Cite

Disparities in care.

Journal Article J Neurosurg · February 2012 Full text Link to item Cite

Avastin: more questions than answers. .

Journal Article J Neurosurg · February 2012 Full text Link to item Cite

Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme.

Journal Article Int J Radiat Oncol Biol Phys · January 1, 2012 PURPOSE: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: A total of 125 patients with newly diagnosed GBM were enrolled in ... Full text Link to item Cite

A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma.

Journal Article PLoS One · 2012 BACKGROUND: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy ... Full text Open Access Link to item Cite

Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma.

Journal Article J Neurooncol · January 2012 We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. A ... Full text Link to item Cite

Toxin-based targeted therapy for malignant brain tumors.

Journal Article Clin Dev Immunol · 2012 Despite advances in conventional treatment modalities for malignant brain tumors-surgery, radiotherapy, and chemotherapy-the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic t ... Full text Open Access Link to item Cite

Application of novel response/progression measures for surgically delivered therapies for gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group.

Journal Article Neurosurgery · January 2012 BACKGROUND: The Response Assessment in Neuro-Oncology (RANO) Working Group is an international, multidisciplinary effort to develop new standardized response criteria for clinical trials in brain tumors. The RANO group identified knowledge gaps relating to ... Full text Link to item Cite

Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.

Journal Article Cancer · December 1, 2011 BACKGROUND: The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, open-label, single-arm trial was evaluated. METHODS: Eligible patients received ca ... Full text Link to item Cite

Radiographic progression of a Chiari I malformation after minor head trauma: Final increment of obstruction to create pathophysiology

Journal Article Journal of Surgical Radiology · December 1, 2011 Introduction The Chiari I malformation is a rare pathological condition that is characterized by a downward herniation of the cerebellar tonsils and brainstem through the foramen magnum. The transformation from an asymptomatic to symptomatic Chiari I malfo ... Cite

A comprehensive outlook on intracerebral therapy of malignant gliomas.

Journal Article Crit Rev Oncol Hematol · October 2011 Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant glioma (MG), with a median survival time of 12-15 months, despite current best treatment based on surgery, radiotherapy and systemic chemotherapy. Many potentially active therapeut ... Full text Link to item Cite

Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans.

Journal Article Blood · September 15, 2011 Lymphodepletion augments adoptive cell transfer during antitumor immunotherapy, producing dramatic clinical responses in patients with malignant melanoma. We report that the lymphopenia induced by the chemotherapeutic agent temozolomide (TMZ) enhances vacc ... Full text Link to item Cite

Convection-enhanced delivery.

Journal Article J Neurosurg · September 2011 Full text Link to item Cite

Colocalization of gadolinium-diethylene triamine pentaacetic acid with high-molecular-weight molecules after intracerebral convection-enhanced delivery in humans.

Journal Article Neurosurgery · September 2011 BACKGROUND: Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monito ... Full text Link to item Cite

Epidemiology.

Journal Article J Neurosurg · August 2011 Full text Link to item Cite

Reply to M.S. Lesniak

Journal Article Journal of Clinical Oncology · August 1, 2011 Full text Cite

Is cytomegalovirus a therapeutic target in glioblastoma?

Journal Article Clin Cancer Res · July 15, 2011 Several investigators have now demonstrated the expression of genes unique to cytomegalovirus (CMV) in malignant gliomas. Many of these genes promote oncogenesis, alter tumor microenvironment, and serve as immunologic targets. Is the level of CMV infection ... Full text Link to item Cite

Bispecific antibodies engage T cells for antitumor immunotherapy.

Journal Article Expert Opin Biol Ther · July 2011 INTRODUCTION: Although considerable evidence supports the hypothesis that T cells play a critical role in the immune response against cancer, the ability to mount and sustain tumor-specific cellular responses in vivo remains a challenge. A strategy that ha ... Full text Link to item Cite

The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma.

Journal Article Clin Cancer Res · June 15, 2011 PURPOSE: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective. EXPERIMENTAL DESIGN: A total of 75 patients ... Full text Link to item Cite

Reply to M.C. Chamberlain

Journal Article Journal of Clinical Oncology · June 10, 2011 Full text Cite

Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.

Journal Article J Neurooncol · June 2011 We evaluated the efficacy of metronomic etoposide or temozolomide administered with bevacizumab among recurrent glioblastoma (GBM) patients who progressed on prior bevacizumab therapy in a phase 2, open-label, two-arm trial. Twenty-three patients received ... Full text Link to item Cite

Resection of vestibular schwannomas.

Journal Article J Neurosurg · May 2011 Full text Link to item Cite

A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma.

Journal Article J Natl Compr Canc Netw · April 2011 Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth fa ... Full text Link to item Cite

Monitoring radiographic brain tumor progression.

Journal Article Toxins (Basel) · March 2011 Determining radiographic progression in primary malignant brain tumors has posed a significant challenge to the neuroncology community. Glioblastoma multiforme (GBM, WHO Grade IV) through its inherent heterogeneous enhancement, growth patterns, and irregul ... Full text Link to item Cite

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma.

Journal Article Neuro Oncol · March 2011 Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic c ... Full text Link to item Cite

Imaging of convection enhanced delivery of toxins in humans.

Journal Article Toxins (Basel) · March 2011 Drug delivery of immunotoxins to brain tumors circumventing the blood brain barrier is a significant challenge. Convection-enhanced delivery (CED) circumvents the blood brain barrier through direct intracerebral application using a hydrostatic pressure gra ... Full text Link to item Cite

A promising cancer vaccine.

Journal Article Future Oncol · March 2011 Full text Link to item Cite

Clinical trial end points for high-grade glioma: the evolving landscape.

Journal Article Neuro Oncol · March 2011 To review the strengths and weaknesses of primary and auxiliary end points for clinical trials among patients with high-grade glioma (HGG). Recent advances in outcome for patients with newly diagnosed and recurrent HGG, coupled with the development of mult ... Full text Link to item Cite

Low-grade glioma.

Journal Article J Neurosurg · March 2011 Full text Link to item Cite

A novel method for volumetric MRI response assessment of enhancing brain tumors.

Journal Article PLoS One · January 26, 2011 Current radiographic response criteria for brain tumors have difficulty describing changes surrounding postoperative resection cavities. Volumetric techniques may offer improved assessment, however usually are time-consuming, subjective and require expert ... Full text Link to item Cite

Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma.

Journal Article J Neurooncol · January 2011 Sorafenib, an oral VEGFR-2, Raf, PDGFR, c-KIT and Flt-3 inhibitor, is active against renal cell and hepatocellular carcinomas, and has recently demonstrated promising activity for lung and breast cancers. In addition, various protracted temozolomide dosing ... Full text Link to item Cite

Immunotherapy coming of age: what will it take to make it standard of care for glioblastoma?

Journal Article Neuro Oncol · January 2011 With the recent approval by the FDA of an immunotherapy for prostate cancer and another positive immunotherapy trial in melanoma, immunotherapy may finally be coming of age. So what will it take for it to become part of the standard treatment for glioblast ... Full text Link to item Cite

Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study.

Journal Article J Neurooncol · January 2011 The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) cath ... Full text Link to item Cite

Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma.

Journal Article J Clin Oncol · November 1, 2010 PURPOSE: Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed ... Full text Link to item Cite

Long-term safety of combined intracerebral delivery of free gadolinium and targeted chemotherapeutic agent PRX321.

Journal Article Neurol Res · October 2010 OBJECTIVES: While convection enhanced delivery (CED) is an effective delivery method that bypasses the blood-brain barrier, its utility is limited by infusate leakage due to catheter misplacement. Therefore, it is critical to evaluate drug distribution dur ... Full text Link to item Cite

Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma.

Journal Article Neuro Oncol · August 2010 Convection-enhanced delivery (CED) of cintredekin besudotox (CB) was compared with Gliadel wafers (GW) in adult patients with glioblastoma multiforme (GBM) at first recurrence. Patients were randomized 2:1 to receive CB or GW. CB (0.5 microg/mL; total flow ... Full text Link to item Cite

Poor drug distribution as a possible explanation for the results of the PRECISE trial.

Journal Article J Neurosurg · August 2010 OBJECT: Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet cl ... Full text Link to item Cite

Bevacizumab fails to treat temporal paraganglioma: discussion and case illustration.

Journal Article J Neurooncol · July 2010 Temporal paragangliomas are highly vascular tumors treated primarily by surgical resection. However, surgery to remove these tumors is associated with significant morbidity, including cranial nerve dysfunction. Interestingly, these tumors have been shown t ... Full text Link to item Cite

Immunotherapy approaches for malignant glioma from 2007 to 2009.

Journal Article Curr Neurol Neurosci Rep · July 2010 Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful, glioma may be an ideal target for immune-based therapy. Recently, translational research ... Full text Link to item Cite

Stereotactic radiosurgery in the treatment of a dural carotid-cavernous fistula.

Journal Article J Neuroophthalmol · June 2010 Because of the success of stereotactic radiosurgery (SRS) in the treatment of cerebral arteriovenous malformations (AVMs), SRS is being applied to the treatment of carotid-cavernous dural arteriovenous fistulas (CCDAVFs) when these lesions are not accessib ... Full text Link to item Cite

Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1.

Journal Article J Neurooncol · May 2010 A major obstacle in glioblastoma (GBM) therapy is the restrictive nature of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) is a novel method of drug administration which allows direct parenchymal infusion of therapeutics, bypassing the B ... Full text Link to item Cite

Convection-enhanced drug delivery to the brain

Journal Article Neuromethods · January 15, 2010 Convection-enhanced delivery (CED) is a method of direct intracerebral parenchymal infusion. It has been previously studied as a mechanism of drug delivery in glioma therapy, which is the focus of this review, and much work has gone into the utilization of ... Full text Cite

Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma.

Journal Article J Neurooncol · January 2010 We evaluated the anti-tumor activity and safety of erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent glioblastoma (GBM) ... Full text Link to item Cite

Clinical applications of a peptide-based vaccine for glioblastoma.

Journal Article Neurosurg Clin N Am · January 2010 Glioblastoma multiforme is a malignant, relentless brain cancer with no known cure, and standard therapies leave significant room for the development of better, more effective treatments. Immunotherapy is a promising approach to the treatment of solid tumo ... Full text Link to item Cite

The role of tregs in glioma-mediated immunosuppression: potential target for intervention.

Journal Article Neurosurg Clin N Am · January 2010 The role of regulatory T cells (Tregs) in mediating immune suppression of anti-tumor immune responses is increasingly appreciated in patients with malignancies-especially within the malignant glioma patient population. This article discuss the role and pro ... Full text Link to item Cite

Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.

Journal Article Br J Cancer · December 15, 2009 BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 ... Full text Open Access Link to item Cite

Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy.

Journal Article J Neurooncol · December 2009 This phase II trial evaluated efficacy and safety of temozolomide (TMZ) in combination with irinotecan (CPT-11) before radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Prior to radiotherapy, patients were treated with a maximum ... Full text Link to item Cite

EGFRvIII-targeted vaccination therapy of malignant glioma.

Journal Article Brain Pathol · October 2009 Given the highly infiltrative growth pattern of malignant glioma and the lack of specificity associated with currently available treatment regimens, alternative strategies designed to eradicate cancer cells while limiting collateral toxicity in normal tiss ... Full text Link to item Cite

An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme.

Journal Article Mol Cancer Ther · October 2009 Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise ... Full text Link to item Cite

Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma.

Journal Article Neuro Oncol · October 2009 This phase I clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG) was designed to determine the maximum tolerated dose (MTD) and toxicity of three different 5-day dosing regimens of temozolomide (TMZ) in combination ... Full text Link to item Cite

Anatomic compression caused by high-volume convection-enhanced delivery to the brain.

Journal Article Neurosurgery · September 2009 OBJECTIVE: Our group has pioneered the use of gadoteridol-loaded liposomes (GDLs) in convection-enhanced delivery (CED) using real-time magnetic resonance imaging (MRI) to visualize the distribution of therapeutic agents in nonhuman primate and canine brai ... Full text Link to item Cite

Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of alpha-particle-emitting (211)At-labeled trastuzumab.

Journal Article Nucl Med Biol · August 2009 INTRODUCTION: Carcinomatous meningitis (CM) is a devastating disease characterized by the dissemination of malignant tumor cells into the subarachnoid space along the brain and spine. Systemic treatment with monoclonal antibody (mAb) trastuzumab can be eff ... Full text Link to item Cite

The PEPvIII-KLH (CDX-110) vaccine in glioblastoma multiforme patients.

Journal Article Expert Opin Biol Ther · August 2009 Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. EGFR variant III ( ... Full text Link to item Cite

IgE, allergy, and risk of glioma: update from the San Francisco Bay Area Adult Glioma Study in the temozolomide era.

Journal Article Int J Cancer · August 1, 2009 The consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that immunoglobulin E (IgE) levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechan ... Full text Link to item Cite

Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma.

Journal Article Cancer · July 1, 2009 BACKGROUND: The current study was a phase 1 clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG). The trial was designed to determine the maximum tolerated dose (MTD) and toxicity of irinotecan (CPT-11) when adminis ... Full text Link to item Cite

Toward effective immunotherapy for the treatment of malignant brain tumors.

Journal Article Neurotherapeutics · July 2009 The immunologic treatment of cancer has long been heralded as a targeted molecular therapeutic with the promise of eradicating tumor cells with minimal damage to surrounding normal tissues. However, a demonstrative example of the efficacy of immunotherapy ... Full text Link to item Cite

Paraganglioma of the head and neck: long-term local control with radiotherapy.

Journal Article Am J Clin Oncol · June 2009 OBJECTIVES: Paragangliomas are rare neuroendocrine neoplasms of the head and neck. Treatment strategies include resection, definitive external beam radiation therapy (EBRT), stereotactic radiosurgery (SRS), or observation alone. Due to their rarity and ind ... Full text Link to item Cite

A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas.

Journal Article J Neurochem · May 2009 Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P incre ... Full text Link to item Cite

Proteomic and immunologic analyses of brain tumor exosomes.

Journal Article FASEB J · May 2009 Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30-100 nm membranous vesicles released from ma ... Full text Link to item Cite

Stereotactic body radiotherapy for lesions of the spine and paraspinal regions.

Journal Article Int J Radiat Oncol Biol Phys · April 1, 2009 PURPOSE: To describe our experience and clinical strategy for stereotactic body radiotherapy (SBRT) of spinal lesions. METHODS AND MATERIALS: Thirty-two patients with 33 spinal lesions underwent computed tomography-based simulation while free breathing. Gr ... Full text Link to item Cite

THE RNA-BINDING PROTEIN 76 CONTROLS GENE EXPRESSION IN GBM

Journal Article NEURO-ONCOLOGY · April 1, 2009 Link to item Cite

Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma.

Journal Article J Clin Oncol · March 10, 2009 PURPOSE: This phase II trial was designed to define the role of O(6)-benzylguanine (O(6)-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administerin ... Full text Link to item Cite

Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme.

Journal Article Clin Cancer Res · February 1, 2009 PURPOSE: This phase II trial was designed to define the efficacy of Gliadel wafers in combination with an infusion of O6-benzylguanine (O6-BG) that suppresses tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in patients with recurrent glioblastoma m ... Full text Link to item Cite

Detection of humoral response in patients with glioblastoma receiving EGFRvIII-KLH vaccines.

Journal Article J Immunol Methods · November 30, 2008 The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in glioblastoma multiforme (GBM) and other neoplasms. As such it represents a truly tumor-specific target for antitumor immunothera ... Full text Link to item Cite

Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas.

Journal Article Clin Cancer Res · November 1, 2008 PURPOSE: Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial ... Full text Link to item Cite

Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery.

Journal Article J Neurosurg · November 2008 OBJECT: The authors have shown that convection-enhanced delivery (CED) of gadoteridol-loaded liposomes (GDLs) into different regions of normal monkey brain results in predictable, widespread distribution of this tracking agent as detected by real-time MR i ... Full text Link to item Cite

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma.

Journal Article Semin Immunol · October 2008 Conventional therapies for malignant gliomas (MGs) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by non-specific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise erad ... Full text Link to item Cite

A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells.

Journal Article Clin Cancer Res · September 15, 2008 PURPOSE: Activation of signal transducers and activators of transcription 3 (STAT3) has been identified as a central mediator of melanoma growth and metastasis. We hypothesized that WP1066, a novel STAT3 blockade agent, has marked antitumor activity, even ... Full text Link to item Cite

Cryptococcal meningitis in patients with glioma: a report of two cases.

Journal Article J Neurooncol · August 2008 OBJECTIVE AND IMPORTANCE: We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the ... Full text Link to item Cite

Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors.

Journal Article Neuro Oncol · June 2008 The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brai ... Full text Link to item Cite

Combating immunosuppression in glioma.

Journal Article Future Oncol · June 2008 Despite maximal therapy, malignant gliomas have a very poor prognosis. Patients with glioma express significant immune defects, including CD4 lymphopenia, increased fractions of regulatory T cells in peripheral blood and shifts in cytokine profiles from Th ... Full text Link to item Cite

Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma.

Journal Article Expert Rev Anticancer Ther · May 2008 Angiogenesis, the growth of new blood vessels from previously existing vasculature, is a requirement for tumor growth and metastasis. The first US FDA-approved drugs targeting angiogenesis have shown potential in the treatment of malignant gliomas. Immunot ... Full text Link to item Cite

Selective modification of antigen-specific T cells by RNA electroporation.

Journal Article Hum Gene Ther · May 2008 It has been observed that the efficient transfection of T cells by RNA electroporation requires prior activation of T cells with mitogens or by anti-CD3 antibody stimulation. We hypothesized that this requirement for T cell activation could be leveraged to ... Full text Link to item Cite

Molecular strategies for the treatment of malignant glioma--genes, viruses, and vaccines.

Journal Article Neurosurg Rev · April 2008 The standard treatment paradigm of surgery, radiation, and chemotherapy for malignant gliomas has only a modest effect on survival. It is well emphasized in the literature that despite aggressive multimodal therapy, most patients survive approximately 1 ye ... Full text Link to item Cite

Immunotherapy of malignant brain tumors.

Journal Article Immunol Rev · April 2008 Despite aggressive multi-modality therapy including surgery, radiation, and chemotherapy, the prognosis for patients with malignant primary brain tumors remains very poor. Moreover, the non-specific nature of conventional therapy for brain tumors often res ... Full text Link to item Cite

Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma.

Journal Article Neuro Oncol · February 2008 Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated ... Full text Link to item Cite

Cholesterol granuloma of the lateral ventricle. Case report.

Journal Article J Neurosurg · February 2008 Cholesterol granulomas (CGs) are benign lesions resulting from an inflammatory reaction to cholesterol and hemosiderin. These masses most often arise within the temporal bone or nasal sinuses; intracerebral CGs are extremely rare. In this report the author ... Full text Link to item Cite

Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: case study.

Journal Article Neuro Oncol · February 2008 Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemotherapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Alt ... Full text Link to item Cite

EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells.

Journal Article Cancer Immunol Immunother · January 2008 PURPOSE: Immunotoxins as anti-cancer therapeutics have several potential advantages over conventional agents including a high specificity, extraordinary potency, and a lack of an identified mechanism for resistance. It has been clearly demonstrated that Ps ... Full text Link to item Cite

Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase 1 study of final safety results.

Journal Article Neurosurgery · November 2007 OBJECTIVE: Cintredekin besudotox (CB), a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13R alpha2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB a ... Full text Link to item Cite

Bevacizumab plus irinotecan in recurrent glioblastoma multiforme.

Journal Article J Clin Oncol · October 20, 2007 PURPOSE: The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irin ... Full text Link to item Cite

Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.

Journal Article Neuro Oncol · July 2007 Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that ... Full text Link to item Cite

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

Journal Article J Neurooncol · May 2007 PURPOSE: Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 s ... Full text Link to item Cite

Viruses in the treatment of malignant glioma.

Journal Article Expert Rev Neurother · April 2007 Full text Link to item Cite

Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function.

Journal Article Clin Cancer Res · April 1, 2007 PURPOSE: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4(+) T cell numbers and function. We have previously shown that increased regulatory T cell (T(reg)) fractions in these p ... Full text Link to item Cite

Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group.

Journal Article J Clin Oncol · March 1, 2007 PURPOSE: Glioblastoma multiforme (GBM) is a devastating brain tumor with a median survival of 6 months after recurrence. Cintredekin besudotox (CB) is a recombinant protein consisting of interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin ( ... Full text Link to item Cite

High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients.

Journal Article Gynecol Oncol · March 2007 PURPOSE: To report our recent experience managing four patients with brain metastases of gestational trophoblastic neoplasia (GTN), coordinating systemic chemotherapy with early neurosurgical intervention or stereotactic radiosurgery and intensive supporti ... Full text Link to item Cite

Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin.

Journal Article AJR Am J Roentgenol · March 2007 OBJECTIVE: Convection-enhanced delivery is a promising approach to intracerebral drug delivery in which a fluid pressure gradient is used to infuse therapeutic macromolecules through an indwelling catheter into the interstitial spaces of the brain. Our pur ... Full text Link to item Cite

Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning.

Journal Article Neurosurgery · February 2007 OBJECTIVE: Convection-enhanced delivery (CED) holds tremendous potential for drug delivery to the brain. However, little is known about the volume of distribution achieved within human brain tissue or how target anatomy and catheter positioning influence d ... Full text Link to item Cite

Genetic analysis of intracranial tumors in a murine model of glioma demonstrate a shift in gene expression in response to host immunity.

Journal Article J Neuroimmunol · January 2007 For the study of malignant glioma, we have previously characterized a highly tumorigenic murine astrocytoma, SMA-560, which arose spontaneously in an inbred, immunocompetent VM/Dk mouse. Using this cell line as a model of murine glioma, we performed DNA mi ... Full text Link to item Cite

Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T cells in patients with malignant glioma reveals differential expression of the immunologic transcriptome compared with T cells from healthy volunteers.

Journal Article Clin Cancer Res · December 15, 2006 PURPOSE: Analyses of T-cell mRNA expression profiles in glioblastoma multiforme has not been previously reported but may help to define and characterize the immunosuppressed phenotype in patients with this type of cancer. EXPERIMENTAL DESIGN: We did microa ... Full text Link to item Cite

Treatment of neoplastic meningitis with intrathecal 9-nitro-camptothecin.

Journal Article Neurol Med Chir (Tokyo) · October 2006 The topoisomerase I inhibitor, 9-nitro-camptothecin (9NC), is highly tumoricidal against glioblastoma multiforme (GBM) in vitro. However, systemic administration of 9NC has not shown the expected efficacy in clinical trials. This failure may be due to the ... Full text Link to item Cite

Preoperative functional MR imaging localization of language and motor areas: effect on therapeutic decision making in patients with potentially resectable brain tumors.

Journal Article Radiology · September 2006 PURPOSE: To prospectively evaluate the effect of preoperative functional magnetic resonance (MR) imaging localization of language and motor areas on therapeutic decision making in patients with potentially resectable brain tumors. MATERIALS AND METHODS: Th ... Full text Link to item Cite

Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells.

Journal Article Clin Cancer Res · July 15, 2006 PURPOSE: Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and eva ... Full text Link to item Cite

Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results.

Journal Article J Nucl Med · June 2006 UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine ... Link to item Cite

Convection-enhanced delivery of therapeutics for brain disease, and its optimization.

Journal Article Neurosurg Focus · April 15, 2006 Convection-enhanced delivery (CED) is the continuous injection under positive pressure of a fluid containing a therapeutic agent. This technique was proposed and introduced by researchers from the US National Institutes of Health (NIH) by the early 1990s t ... Full text Link to item Cite

Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.

Journal Article Neurosurg Focus · April 15, 2006 OBJECT: Convection-enhanced delivery (CED) is an increasingly used novel local/regional delivery method targeted directly to tissue. It relies on a continuous pressure gradient for distribution of therapeutic agents into the interstitial space, with admini ... Link to item Cite

Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies.

Journal Article Neurosurg Focus · April 15, 2006 OBJECTIVES: Convection-enhanced delivery (CED) is a novel technique used to deliver agents to the brain parenchyma for treatment of neoplastic, infectious, and degenerative conditions. The purpose of this study was to determine if CED would provide a large ... Full text Link to item Cite

Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.

Journal Article Cancer Res · March 15, 2006 Immunosuppression is frequently associated with malignancy and is particularly severe in patients with malignant glioma. Anergy and counterproductive shifts toward T(H)2 cytokine production are long-recognized T-cell defects in these patients whose etiolog ... Full text Link to item Cite

Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus.

Journal Article Clin Cancer Res · February 15, 2006 PURPOSE: The toxicity and antitumor activity of regional intrathecal delivery of an oncolytic recombinant poliovirus, PVS-RIPO, was evaluated in rodent models of glioblastoma multiforme neoplastic meningitis. EXPERIMENTAL DESIGN: To evaluate for toxicity, ... Full text Link to item Cite

Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma.

Journal Article Clin Cancer Res · February 1, 2006 PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among pat ... Full text Link to item Cite

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

Journal Article J Clin Oncol · December 20, 2005 PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiform ... Full text Link to item Cite

Brain metastases from malignant melanoma

Journal Article · December 1, 2005 Full text Cite

Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

Journal Article J Clin Oncol · October 1, 2005 PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The ... Full text Link to item Cite

Surgical management of petroclival meningiomas: defining resection goals based on risk of neurological morbidity and tumor recurrence rates in 137 patients.

Journal Article Neurosurgery · March 2005 OBJECTIVE: Meningiomas arising from the petroclival region remain a challenging surgical problem. Because of the substantial risk of neurological morbidity, uniformly pursuing a gross total resection (GTR) to minimize tumor recurrence rates may not be just ... Full text Link to item Cite

Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study.

Journal Article Neuro Oncol · January 2005 Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to tra ... Full text Link to item Cite

Treatment of intracerebral neoplasia and neoplastic meningitis with regional delivery of oncolytic recombinant poliovirus.

Journal Article Clin Cancer Res · July 15, 2004 PURPOSE: Spread to the central nervous system (CNS) and the leptomeninges is a frequent complication of systemic cancers that is associated with serious morbidity and high mortality. We have evaluated a novel therapeutic approach against CNS complications ... Full text Link to item Cite

Poliovirus receptor CD155-targeted oncolysis of glioma.

Journal Article Neuro Oncol · July 2004 Cell adhesion molecules of the immunoglobulin superfamily are aberrantly expressed in malignant glioma. Amongst these, the human poliovirus receptor CD155 provides a molecular target for therapeutic intervention with oncolytic poliovirus recombinants. Poli ... Full text Link to item Cite

Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme.

Journal Article Clin Cancer Res · May 1, 2004 PURPOSE: We have reported previously that tumors expressing wild-type epidermal growth factor receptor (EGFR) in a murine model are sensitive to the EGFR tyrosine kinase inhibitor gefitinib, whereas tumors expressing mutant EGFR variant III (EGFRvIII) are ... Full text Link to item Cite

Microvascular decompression for glossopharyngeal neuralgia: long-term effectiveness and complication avoidance.

Journal Article Neurosurgery · April 2004 OBJECTIVE: To establish the long-term safety, efficacy, and durability of microvascular decompression (MVD) for the treatment of glossopharyngeal neuralgia, this study presents the immediate (<6 mo) postoperative and long-term results of a large series of ... Full text Link to item Cite

Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma.

Journal Article Neuro Oncol · April 2004 Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or prog ... Full text Link to item Cite

Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma.

Journal Article Neuro Oncol · April 2004 In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administere ... Full text Link to item Cite

Novel therapeutic approaches for high-grade gliomas

Chapter · January 1, 2004 The incidence of primary brain tumors is increasing. Approximately 18,000 new cases were expected in the U.S. in 2003.1 High-grade gliomas (HGGs) including glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) are the most common primary tumors of ... Cite

In vitro cytotoxic activity of Thai medicinal plants used traditionally to treat cancer.

Journal Article Journal of ethnopharmacology · January 2004 The SRB assay was used to test cytotoxicity against three human cancer cell lines and one normal cell line of 11 Thai medicinal plant species used by traditional doctors in treating cancer patients. The extraction procedures used were similar to those prac ... Cite

Phase II trial of gefitinib in recurrent glioblastoma.

Journal Article J Clin Oncol · January 1, 2004 PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an op ... Full text Link to item Cite

Immunotherapy of surgical malignancies.

Journal Article Curr Probl Surg · January 2004 Full text Link to item Cite

Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer.

Journal Article Clin Cancer Res · November 15, 2003 PURPOSE: The monoclonal antibody (MAb) trastuzumab (Herceptin) effectively treats HER2-overexpressing extracerebral breast neoplasms. Delivery of such macromolecule therapeutic agents to intracerebral metastases, however, is limited by the tight junctions ... Link to item Cite

Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors.

Journal Article J Neurooncol · October 2003 TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maxim ... Full text Link to item Cite

Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.

Journal Article Clin Cancer Res · September 15, 2003 PURPOSE: The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse ... Link to item Cite

Phase II trial of temozolomide in patients with progressive low-grade glioma.

Journal Article J Clin Oncol · February 15, 2003 PURPOSE: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studi ... Full text Link to item Cite

Adoptive immunotherapy for malignant glioma.

Journal Article Cancer J · 2003 Despite remarkable advancements in imaging modalities and treatment options available to patients diagnosed with malignant brain tumors, the prognosis for those with high-grade lesions remains poor. The imprecise mechanisms of currently available treatment ... Full text Link to item Cite

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Journal Article J Neurooncol · 2003 Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific t ... Full text Link to item Cite

Clinical immunotherapy for brain tumors.

Journal Article Neuroimaging Clin N Am · November 2002 As an immunization platform for brain tumors, dendritic cells supply an impressive host of advantages. On the simplest level, they provide the safety and tumor-specificity so wanted by current therapeutic options. Yet, in addition, as the fundamental antig ... Full text Link to item Cite

Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa).

Journal Article Clin Cancer Res · November 2002 Featured Publication Iressa (ZD1839) is a p.o.-active, selective, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways implicated in cancer cell proliferation, survival, and host-dependent processes promoting cancer gro ... Link to item Cite

Viruses in the treatment of brain tumors.

Journal Article Neuroimaging Clin N Am · November 2002 The grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. Viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vecto ... Full text Link to item Cite

Intracanalicular meningioma mimicking vestibular schwannoma.

Journal Article AJNR Am J Neuroradiol · October 2002 Featured Publication Three cases of intracanalicular meningioma mimicking vestibular schwannoma are presented. In each case, a contrast-enhancing mass filling the internal auditory canal was identified on MR images and was originally diagnosed as a vestibular schwannoma. Altho ... Link to item Cite

Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion.

Journal Article Cancer Res · June 15, 2002 Featured Publication The gene most commonly altered in human glioblastomas is the epidermalgrowth factor receptor (EGFR). We profiled transcripts induced by mutantEGFR to better understand its role in tumor progression. The pattern found suggested enhanced tumor invasion. The ... Link to item Cite

Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma.

Journal Article J Clin Oncol · May 1, 2002 Featured Publication PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O(6)-alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent ... Full text Link to item Cite

Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas.

Journal Article J Clin Oncol · March 1, 2002 Featured Publication PURPOSE: To assess the efficacy and toxicity of intraresection cavity (131)I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase ... Full text Link to item Cite

Generation of anti-idiotypic reagents in the EGFRvIII tumor-associated antigen system.

Journal Article Cancer Immunol Immunother · February 2002 Featured Publication The use of anti-idiotype (anti-id) vaccines for immunotherapy of human cancers is attractive, as immunization with true anti-id reagents (Ab2 beta) has been shown to induce both cellular and humoral immunity, frequently when the original antigen does not, ... Full text Link to item Cite

Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

Journal Article Neurosurgery · January 2002 Featured Publication OBJECTIVE: Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by D ... Full text Link to item Cite

Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas.

Journal Article Neuro Oncol · October 2001 Both Gliadel wafers [1,3-bis(2-chloroethyl)-1-nitrosourea] and temozolomide (TEMO) have been shown in independent studies to prolong survival of patients with recurrent malignant glioma following surgery and radiotherapy. On the basis of preclinical eviden ... Full text Link to item Cite

In vitro keratinocyte antiproliferant effect of Centella asiatica extract and triterpenoid saponins.

Journal Article Phytomedicine · May 2001 Psoriasis is a hyperproliferative skin disorder estimated to be present in 1-3% of most populations. Conventional therapy using corticosteroids, Vitamin D analogs and cytotoxic agents eg psoralens is associated with low success rate and many side effects. ... Full text Link to item Cite

Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

Journal Article J Clin Oncol · October 15, 2000 PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O(6) position of guanine. O(6)-benzylguanine ... Full text Link to item Cite

Temozolomide delivered by intracerebral microinfusion is safe and efficacious against malignant gliomas in rats.

Journal Article Clin Cancer Res · October 2000 Intracerebral microinfusion (ICM) is an innovative technique of delivering therapeutic agents throughout large portions of the brain that circumvents the blood-brain barrier, minimizes systemic toxicity, and provides a homogeneous distribution of the infus ... Link to item Cite

EGFRvIII: An oncogene deletion mutant cell surface receptor target expressed by multiple tumour types

Journal Article Expert Opinion on Therapeutic Targets · August 1, 2000 Optimal immunotherapeutic approaches to cancer cell eradication require the specific recognition of neoplastic cells and minimal destruction of bystander, normal cells. This is especially crucial within the CNS because of the infiltrative growth pattern of ... Full text Cite

Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors.

Journal Article Proc Natl Acad Sci U S A · June 20, 2000 The epidermal growth factor receptor (EGFR) is often amplified and rearranged structurally in tumors of the brain, breast, lung, and ovary. The most common mutation, EGFRvIII, is characterized by an in-frame deletion of 801 base pairs, resulting in the gen ... Full text Link to item Cite

Ethnomedicinally selected plants as sources of potential analgesic compounds: indication of in vitro biological activity in receptor binding assays.

Journal Article Phytother Res · February 2000 A number of plant species used in traditional medicine for the relief of pain have been selected from the medicinal and scientific literature of China, South America, Asia and West Africa. Extracts were prepared and tested in three in vitro receptor radiol ... Full text Link to item Cite

Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma.

Journal Article J Neuroimmunol · February 1, 2000 To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell line derived from an astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morp ... Full text Link to item Cite

Regional treatment of epidermal growth factor receptor vIII-expressing neoplastic meningitis with a single-chain immunotoxin, MR-1.

Journal Article Clin Cancer Res · September 1999 The incidence of neoplastic meningitis is on the rise. Neoplastic meningitis can result from a direct seeding of the neuraxis by primary brain tumors or by hematogeneous spread of systemic solid tumors. A frequent genetic alteration in primary brain tumors ... Link to item Cite

Treatment of neoplastic meningitis with intrathecal temozolomide.

Journal Article Clin Cancer Res · May 1999 Featured Publication Neoplastic meningitis (NM) results from leptomeningeal dissemination of cancers arising within the central nervous system or metastasizing to the leptomeninges from systemic neoplasms. The inability to produce therapeutic drug levels intrathecally (i.t.) w ... Link to item Cite

Monoclonal antibody therapy of human gliomas: current status and future approaches.

Journal Article Cancer Metastasis Rev · 1999 The development of immunotherapeutic protocols for the treatment of human CNS neoplasia over the past two decades has been impressive. Several crucial aspects have been defined, characterized, and in many cases, optimized (Wikstrand CJ, Zalutsky MR, Bigner ... Full text Link to item Cite

Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.

Journal Article J Neurooncol · 1999 The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated thr ... Full text Link to item Cite

Experience with a cross-study endpoint review committee for AIDS clinical trials. Terry Beirn Community Programs for Clinical Research on AIDS.

Journal Article AIDS · October 22, 1998 OBJECTIVES: To describe the methods and results of a standardized system for clinical endpoint determination for defining and reviewing endpoints in clinical trials for HIV-infected individuals. DESIGN: A system was developed utilizing standard definitions ... Full text Link to item Cite

Local production of TGF beta1 inhibits cerebral edema, enhances TNF-alpha induced apoptosis and improves survival in a murine glioma model.

Journal Article J Neuroimmunol · June 1, 1998 We have previously reported that local secretion of either TNF-alpha or TGF beta1 by intracerebral SMA-560 malignant glioma tumor cells can reduce or eliminate tumor growth in mice. However, the use of TNF-alpha, while improving the overall survival of tum ... Full text Link to item Cite

A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. Terry Beirn Community Programs for Clinical Research on AIDS.

Journal Article AIDS · February 12, 1998 OBJECTIVE: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV disease. DESIGN: Double-blind, placebo-controlled, randomized clinical trial in primary care clinics ... Full text Link to item Cite

Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma.

Journal Article J Neurosurg · January 1998 Featured Publication UNLABELLED: Brain metastases are a common and devastating complication in patients with malignant melanoma. Therapeutic options for these patients are limited, and the prognosis is usually poor. OBJECT: A retrospective review of 6953 patients with melanoma ... Full text Link to item Cite

Characterization of a spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion.

Journal Article Neurosurgery · December 1997 OBJECTIVE: The promise of immunotherapies developed against brain tumors in animal models has not been realized in human clinical trials. This may be because of the routine use of rodent tumors artificially induced by chemicals or viruses that do not accur ... Full text Link to item Cite

A genetically modified allogeneic cellular vaccine generates MHC class I-restricted cytotoxic responses against tumor-associated antigens and protects against CNS tumors in vivo.

Journal Article J Neuroimmunol · September 1997 An active immunotherapeutic strategy using transfected allogeneic cells for targeting the mutant epidermal growth factor receptor (EGFRvIII) on intracranial tumors was examined. Immunization with allogeneic 300.19/EGFRvIII cells induced CD8+ cytotoxic T-ly ... Full text Link to item Cite

Viruses and oncogenes in brain tumors.

Journal Article J Neurovirol · May 1997 Link to item Cite

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative.

Journal Article AIDS Res Hum Retroviruses · March 1, 1997 This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight a ... Full text Link to item Cite

The impact of human immunodeficiency virus infection on drug-resistant tuberculosis.

Journal Article Am J Respir Crit Care Med · November 1996 Infection with human immunodeficiency virus (HIV) has been associated with increased rates of single- and multidrug-resistant (MDR) tuberculosis in the New York City area. In order to examine the relationship of HIV infection to drug-resistant tuberculosis ... Full text Link to item Cite

Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.

Journal Article Proc Natl Acad Sci U S A · September 17, 1996 Featured Publication Vaccination with cytokine-producing tumor cells generates potent immune responses against tumors outside the central nervous system (CNS). The CNS, however, is a barrier to allograft and xenograft rejection, and established tumors within the CNS have faile ... Full text Link to item Cite

Recurrence of a cerebral arteriovenous malformation after surgical excision. Case report.

Journal Article J Neurosurg · May 1996 Complete excision of a cerebral arteriovenous malformation (AVM) should eliminate the future risk of an associated intracranial hemorrhage. Because total removal of an AVM may be difficult to assess at the time of surgery, postoperative angiography has bec ... Full text Link to item Cite

Glomus jugulare tumor metastatic to the sacrum after high-dose radiation therapy: case report.

Journal Article Neurosurgery · November 1995 A 47-year-old woman with left ear pain and hearing loss was diagnosed with a glomus jugulare tumor for which she received radiation therapy as the primary treatment. Over a period of 20 years, she developed temporal bone necrosis, brain stem calcifications ... Full text Link to item Cite

Metastatic melanoma to the spine. Demographics, risk factors, and prognosis in 114 patients.

Journal Article Spine (Phila Pa 1976) · October 1, 1995 STUDY DESIGN: One-hundred-fourteen patients with metastatic melanoma of the spine were retrospectively reviewed. OBJECTIVE: The goal was to define the demographics, risk factors, and prognosis for this population. SUMMARY OF BACKGROUND DATA: The incidence ... Full text Link to item Cite

Dorsal root entry zone lesions for intractable pain after trauma to the conus medullaris and cauda equina.

Journal Article J Neurosurg · January 1995 This review was undertaken to determine the efficacy of using dorsal root entry zone (DREZ) lesions to treat intractable pain caused by trauma to the conus medullaris and cauda equina. Traumatic lesions of this area are unique in that both the spinal cord ... Full text Link to item Cite

On being poor with HIV.

Journal Article Lancet · October 22, 1994 Full text Link to item Cite

Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group.

Journal Article Ann Intern Med · August 1, 1994 OBJECTIVE: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodefici ... Full text Link to item Cite

The gravitational shunt: an alternative approach to cerebrospinal fluid shunting.

Journal Article Surg Neurol · August 1993 Current cerebrospinal fluid shunts use complex differential pressure values to regulate drainage. Such systems are prone to overdrainage and obstruction, and thus have an unpredictable effect on intracranial pressure (ICP). The gravitational shunt (GS) int ... Full text Link to item Cite

Epidural spinal metastases from malignant melanoma: Demographics, prognosis and treatment.

Journal Article Canadian Journal of Neurological Sciences · 1993 Cite

Solitary eosinophilic granuloma invading the clivus of an adult: case report.

Journal Article Neurosurgery · October 1992 A 41-year-old white man with facial pain and diplopia was found to have an invasive lesion of the clivus. The final pathological diagnosis was eosinophilic granuloma. The patient's symptoms resolved completely after transsphenoidal resection of the lesion. ... Full text Link to item Cite

Facial pain due to vascular lesions of the brain stem relieved by dorsal root entry zone lesions in the nucleus caudalis. Report of two cases.

Journal Article J Neurosurg · September 1992 One patient with a pontine infarct due to a fusiform basilar artery aneurysm and one with an arteriovenous malformation within the tectum of the mesencephalon developed intractable facial pain. This pain was relieved in both patients by radiofrequency lesi ... Full text Link to item Cite

Initial management of pediatric head trauma.

Journal Article Am Fam Physician · June 1992 Head injuries are the most common cause of disability and death in children. Identification of children who require specialized management following a head injury will reduce the associated morbidity and mortality. Thus, it is important to differentiate th ... Link to item Cite