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Article ; Online: Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.

2023 Volume 15, Issue 682, Page(s) eabn5649

Abstract: D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized ... ...

Abstract	D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized that immunosuppression in glioblastoma limits D2C7-IT efficacy. To improve the response rate and reverse immunosuppression, we combined D2C7-IT tumor cell killing with αCD40 costimulation of antigen-presenting cells. In murine glioma models, a single intratumoral injection of D2C7-IT+αCD40 treatment activated a proinflammatory phenotype in microglia and macrophages, promoted long-term tumor-specific CD8
MeSH term(s)	Humans ; Animals ; Mice ; Glioblastoma/pathology ; Immunotoxins/genetics ; CD8-Positive T-Lymphocytes ; Adaptive Immunity ; Glioma ; ErbB Receptors/metabolism ; Cell Line, Tumor ; Brain Neoplasms/therapy
Chemical Substances	Immunotoxins ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2023-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abn5649
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Article ; Online: Recombinant polio-rhinovirus immunotherapy for recurrent paediatric high-grade glioma: a phase 1b trial.

The Lancet. Child & adolescent health

2023 Volume 7, Issue 7, Page(s) 471–478

Abstract: Background: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent ... ...

Abstract	Background: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric high-grade glioma and has shown promise in adults with recurrent glioblastoma. The poliovirus receptor CD155 is ubiquitously expressed in malignant paediatric brain tumours and is a treatment target in paediatric high-grade glioma. We aimed to assess the safety of lerapolturev when administered as a single dose intracerebrally by convection enhanced delivery in children and young people with recurrent WHO grade 3 or grade 4 glioma, and to assess overall survival in these patients. Methods: This phase 1b trial was done at the Duke University Medical Center (Durham, NC, USA). Patients aged 4-21 years with recurrent high-grade malignant glioma (anaplastic astrocytoma, glioblastoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic pleomorphic xanthoastrocytoma) or anaplastic ependymoma, atypical teratoid rhabdoid tumour, or medulloblastoma with infusible disease were eligible for this study. A catheter was tunnelled beneath the scalp for a distance of at least 5 cm to aid in prevention of infection. The next day, lerapolturev at a dose of 5 × 10 Findings: Between Dec 5, 2017, and May 12, 2021, 12 patients (11 unique patients) were enrolled in the trial. Eight patients were treated with lerapolturev. The median patient age was 16·5 years (IQR 11·0-18·0), five (63%) of eight patients were male and three (38%) were female, and six (75%) of eight patients were White and two (25%) were Black or African American. The median number of previous chemotherapeutic regimens was 3·50 (IQR 1·25-5·00). Six of eight patients had 26 treatment-related adverse events attributable to lerapolturev. There were no irreversible (ie, persisted longer than 2 weeks) treatment-related grade 4 adverse events or deaths. Treatment-related grade 3 adverse events included headaches in two patients and seizure in one patient. Four patients received low-dose bevacizumab on-study for treatment-related peritumoural inflammation or oedema, diagnosed by both clinical symptoms plus fluid-attenuated inversion recovery MRI. The median overall survival was 4·1 months (95% CI 1·2-10·1). One patient remains alive after 22 months. Interpretation: Convection enhanced delivery of lerapolturev is safe enough in the treatment of recurrent paediatric high-grade glioma to proceed to the next phase of trial. Funding: Solving Kids Cancer, B+ Foundation, Musella Foundation, and National Institutes of Health.
MeSH term(s)	Adult ; Humans ; Child ; Male ; Female ; Adolescent ; Glioblastoma ; Rhinovirus ; Neoplasm Recurrence, Local/therapy ; Glioma/drug therapy ; Brain Neoplasms/therapy ; Immunotherapy ; Astrocytoma ; Poliomyelitis ; Cerebellar Neoplasms
Language	English
Publishing date	2023-03-30
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2352-4650
ISSN (online)	2352-4650
DOI	10.1016/S2352-4642(23)00031-7
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Article ; Online: Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas.

Diplas, Bill H / Liu, Heng / Yang, Rui / Hansen, Landon J / Zachem, Alexis L / Zhao, Fangping / Bigner, Darell D / McLendon, Roger E / Jiao, Yuchen / He, Yiping / Waitkus, Matthew S / Yan, Hai

Neuro-oncology

2018 Volume 21, Issue 4, Page(s) 440–450

Abstract: Background: Mutations in telomerase reverse transcriptase promoter (TERTp) and isocitrate dehydrogenase 1 and 2 (IDH) offer objective markers to assist in classifying diffuse gliomas into genetic subgroups. However, traditional mutation detection ... ...

Abstract	Background: Mutations in telomerase reverse transcriptase promoter (TERTp) and isocitrate dehydrogenase 1 and 2 (IDH) offer objective markers to assist in classifying diffuse gliomas into genetic subgroups. However, traditional mutation detection techniques lack sensitivity or have long turnaround times or high costs. We developed GliomaDx, an allele-specific, locked nucleic acid-based quantitative PCR assay to overcome these limitations and sensitively detect TERTp and IDH mutations. Methods: We evaluated the performance of GliomaDx on cell line DNA and frozen tissue diffuse glioma samples with variable tumor percentage to mimic use in clinical settings and validated low percentage variants using sensitive techniques including droplet digital PCR (ddPCR) and next-generation sequencing. We also developed GliomaDx Nest, which incorporates a high-fidelity multiplex pre-amplification step prior to allele-specific PCR for low-input formalin-fixed paraffin embedded (FFPE) samples. Results: GliomaDx detects the TERTp and IDH1 alterations at an analytical sensitivity of 0.1% mutant allele fraction, corresponding to 0.2% tumor cellularity. GliomaDx identified TERTp/IDH1 alterations in a cohort of frozen tissue samples with variable tumor percentage of all major diffuse glioma histologic types. GliomaDx Nest is able to detect these hotspot mutations with similar sensitivity from pre-amplified samples and was successfully tested on a cohort of clinical FFPE samples. Testing of a cohort of previously identified TERTpWT-IDHWT gliomas (by Sanger sequencing) revealed that 26.3% harbored low-percentage mutations. Analysis by ddPCR and whole exome sequencing of these tumors confirmed the low mutant fraction of these alterations and overall mutation-based tumor purity. Conclusions: Our results show that GliomaDx can rapidly detect TERTp/IDH mutations with high sensitivity, identifying cases that might be missed due to the lack of sensitivity of other techniques. This approach may facilitate more objective classification of diffuse glioma samples in clinical settings such as intraoperative diagnosis or in testing cases with low tumor purity.
MeSH term(s)	Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Brain Neoplasms/genetics ; DNA Mutational Analysis/methods ; Glioma/genetics ; Humans ; Isocitrate Dehydrogenase/genetics ; Mutation ; Promoter Regions, Genetic ; Real-Time Polymerase Chain Reaction/methods ; Telomerase/genetics
Chemical Substances	Biomarkers, Tumor ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.) ; TERT protein, human (EC 2.7.7.49) ; Telomerase (EC 2.7.7.49)
Language	English
Publishing date	2018-10-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noy167
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Zs.A 5307: Show issues

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Article ; Online: MGMT: Immunohistochemical Detection in High-Grade Astrocytomas.

Lipp, Eric S / Healy, Patrick / Austin, Alan / Clark, Alysha / Dalton, Tara / Perkinson, Kathryn / Herndon, James E / Friedman, Henry S / Friedman, Allan H / Bigner, Darell D / McLendon, Roger E

Journal of neuropathology and experimental neurology

2018 Volume 78, Issue 1, Page(s) 57–64

Abstract: Glioma therapeutic resistance to alkylating chemotherapy is mediated via O6-methylguanine-DNA methyltransferase (MGMT). We hypothesized that a CD45/HAM56/MGMT double-stained cocktail would improve MGMT discrimination in tumor cells versus inflammatory ... ...

Abstract	Glioma therapeutic resistance to alkylating chemotherapy is mediated via O6-methylguanine-DNA methyltransferase (MGMT). We hypothesized that a CD45/HAM56/MGMT double-stained cocktail would improve MGMT discrimination in tumor cells versus inflammatory and endothelial cells (IEC). Total MGMT protein was quantified by IHC on 982 glioblastomas (GBM) and 199 anaplastic astrocytomas. Correcting for IEC was done by a CD45/HAM56/MGMT 2-color cocktail. Lowest IEC infiltrates (IEC "cold spots") were identified to quantitate MGMT as well as the percentage of IEC% in the IEC cold spots. MGMT promoter methylation (PM) was also determined. Among the GBM biopsies, mean uncorrected and corrected MGMT% were 19.87 (range 0-90) and 16.67; mean IEC% was 18.65 (range 1-80). Four hundred and fifty one (45.9%) GBM biopsies were positive MGMT PM. Both uncorrected and corrected MGMT% positivity correlated with PM. All 3 MGMT scores correlated with overall survival (OS) in GBM's. Cold spot IEC% was also positively associated with OS. These effects remained in a multivariate model after adjusting for age and disease status. Prognosis determined by correcting MGMT% score for IEC% is not improved in this analysis. However, IEC COLD SPOT score does provide additional prognostic information that can be gained from this correction method.
MeSH term(s)	Adult ; Aged ; Astrocytoma/genetics ; Biomarkers, Tumor/analysis ; Brain Neoplasms/genetics ; DNA Methylation ; DNA Modification Methylases/analysis ; DNA Modification Methylases/genetics ; DNA Repair Enzymes/analysis ; DNA Repair Enzymes/genetics ; Female ; Humans ; Immunohistochemistry/methods ; Male ; Middle Aged ; Tumor Suppressor Proteins/analysis ; Tumor Suppressor Proteins/genetics
Chemical Substances	Biomarkers, Tumor ; Tumor Suppressor Proteins ; DNA Modification Methylases (EC 2.1.1.-) ; MGMT protein, human (EC 2.1.1.63) ; DNA Repair Enzymes (EC 6.5.1.-)
Language	English
Publishing date	2018-11-23
Publishing country	England
Document type	Journal Article
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nly110
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Ui II Zs.134: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Ui II Zs.194: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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Article: Cerebrospinal fluid (CSF) cytology: current status and diagnostic applications.

Bigner, S H

Journal of neuropathology and experimental neurology

1992 Volume 51, Issue 3, Page(s) 235–245

Abstract: Cytologic evaluation of cerebrospinal fluid (CSF) is an effective means for diagnosing many disorders involving the central nervous system (CNS). Interpretation of these samples requires an understanding of the spectrum of neurologic diseases which ... ...

Abstract	Cytologic evaluation of cerebrospinal fluid (CSF) is an effective means for diagnosing many disorders involving the central nervous system (CNS). Interpretation of these samples requires an understanding of the spectrum of neurologic diseases which involves the subarachnoid space, either primarily or secondarily, as well as familiarity with the cytologic characteristics of these lesions. Here the clinical features and cytologic presentation of common conditions which can be diagnosed by CSF cytology are reviewed. Preparatory methods for CSF examination are discussed and normal and reactive conditions involving CSF, lymphoma, leukemia, meningeal carcinomatosis and the subarachnoid spread of primary brain tumors are described and illustrated.
MeSH term(s)	Carcinoma/cerebrospinal fluid ; Central Nervous System Diseases/diagnosis ; Central Nervous System Neoplasms/cerebrospinal fluid ; Central Nervous System Neoplasms/secondary ; Cerebrospinal Fluid/cytology ; Humans ; Immunohistochemistry/methods ; Infection/cerebrospinal fluid ; Leukemia/pathology ; Lymphoma/pathology ; Meningeal Neoplasms/cerebrospinal fluid ; Molecular Biology/methods
Language	English
Publishing date	1992-05
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1097/00005072-199205000-00001
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Ui II Zs.194: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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

Gromeier, Matthias / Brown, Michael C / Zhang, Gao / Lin, Xiang / Chen, Yeqing / Wei, Zhi / Beaubier, Nike / Yan, Hai / He, Yiping / Desjardins, Annick / Herndon, James E / Varn, Frederick S / Verhaak, Roel G / Zhao, Junfei / Bolognesi, Dani P / Friedman, Allan H / Friedman, Henry S / McSherry, Frances / Muscat, Andrea M /

Lipp, Eric S / Nair, Smita K / Khasraw, Mustafa / Peters, Katherine B / Randazzo, Dina / Sampson, John H / McLendon, Roger E / Bigner, Darell D / Ashley, David M

Nature communications

2021 Volume 12, Issue 1, Page(s) 352

Abstract: 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 ... ...

Abstract	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 immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.
MeSH term(s)	Biomarkers, Tumor/genetics ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Brain Neoplasms/therapy ; Cohort Studies ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Genomics/methods ; Glioblastoma/genetics ; Glioblastoma/pathology ; Glioblastoma/therapy ; Humans ; Immunotherapy/methods ; Inflammation/genetics ; Mutation ; Neoplasm Recurrence, Local ; Oncolytic Virotherapy/methods ; Outcome Assessment, Health Care/methods ; Outcome Assessment, Health Care/statistics & numerical data ; Proportional Hazards Models ; Survival Analysis
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2021-01-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-20469-6
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Article: Molecular probes in neuro-oncology: the future.

Bigner, S H

Cancer investigation

1990 Volume 8, Issue 3-4, Page(s) 445–446

MeSH term(s)	Molecular Probes ; Nervous System Neoplasms/genetics
Chemical Substances	Molecular Probes
Language	English
Publishing date	1990
Publishing country	England
Document type	Editorial ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	604942-4
ISSN	0735-7907
ISSN	0735-7907
DOI	10.3109/07357909009012064
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Zs.A 1862: Show issues

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Article ; Online: Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations.

Chandramohan, Vidyalakshmi / Bao, Xuhui / Yu, Xin / Parker, Scott / McDowall, Charlotte / Yu, Yen-Rei / Healy, Patrick / Desjardins, Annick / Gunn, Michael D / Gromeier, Matthias / Nair, Smita K / Pastan, Ira H / Bigner, Darell D

Journal for immunotherapy of cancer

2019 Volume 7, Issue 1, Page(s) 142

Abstract: Background: D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma. In addition to inherent tumoricidal activity, immunotoxins induce secondary ... ...

Abstract	Background: D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma. In addition to inherent tumoricidal activity, immunotoxins induce secondary immune responses through the activation of T cells. However, glioblastoma-induced immune suppression is a major obstacle to an effective and durable immunotoxin-mediated antitumor response. We hypothesized that D2C7-IT-induced immune response could be effectively augmented in combination with αCTLA-4/αPD-1/αPD-L1 therapies in murine models of glioma. Methods: To study this, we overexpressed the D2C7-IT antigen, murine EGFRvIII (dmEGFRvIII), in established glioma lines, CT-2A and SMA560. The reactivity and therapeutic efficacy of D2C7-IT against CT-2A-dmEGFRvIII and SMA560-dmEGFRvIII cells was determined by flow cytometry and in vitro cytotoxicity assays, respectively. Antitumor efficacy of D2C7-IT was examined in immunocompetent, intracranial murine glioma models and the role of T cells was assessed by CD4+ and CD8+ T cell depletion. In vivo efficacy of D2C7-IT/αCTLA-4/αPD-1 monotherapy or D2C7-IT+αCTLA-4/αPD-1 combination therapy was evaluated in subcutaneous unilateral and bilateral CT-2A-dmEGFRvIII glioma-bearing immunocompetent mice. Further, antitumor efficacy of D2C7-IT+αCTLA-4/αPD-1/αPD-L1/αTim-3/αLag-3/αCD73 combination therapy was evaluated in intracranial CT-2A-dmEGFRvIII and SMA560-dmEGFRvIII glioma-bearing mice. Pairwise differences in survival curves were assessed using the generalized Wilcoxon test. Results: D2C7-IT effectively killed CT-2A-dmEGFRvIII (IC Conclusions: These data support the development of D2C7-IT and immune checkpoint blockade combinations for patients with malignant glioma.
MeSH term(s)	Animals ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Disease Models, Animal ; ErbB Receptors/pharmacology ; ErbB Receptors/therapeutic use ; Female ; Humans ; Immunotoxins/drug effects ; Mice ; Mice, Inbred C57BL
Chemical Substances	Immunotoxins ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2019-05-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1186/s40425-019-0614-0
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Article ; Online: Cic

Yang, Rui / Chen, Lee H / Hansen, Landon J / Carpenter, Austin B / Moure, Casey J / Liu, Heng / Pirozzi, Christopher J / Diplas, Bill H / Waitkus, Matthew S / Greer, Paula K / Zhu, Huishan / McLendon, Roger E / Bigner, Darell D / He, Yiping / Yan, Hai

Cancer research

2017 Volume 77, Issue 22, Page(s) 6097–6108

Abstract: Inactivating mutations in the transcriptional repression ... ...

Abstract	Inactivating mutations in the transcriptional repression factor
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cells, Cultured ; Gene Expression Profiling/methods ; Humans ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Mice, Transgenic ; Mutation ; Neural Stem Cells/metabolism ; Oligodendroglioma/genetics ; Oligodendroglioma/pathology ; Repressor Proteins/genetics
Chemical Substances	CIC protein, human ; Cic protein, mouse ; Repressor Proteins
Language	English
Publishing date	2017-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-17-1018
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Article: Cyclophosphamide therapy of medulloblastoma: from the laboratory to the clinic and back again (and again and again).

Friedman, H S / Bigner, S H / Bigner, D D

Journal of neuro-oncology

1995 Volume 24, Issue 1, Page(s) 103–108

Abstract: Medulloblastoma, the most common malignancy of childhood, was originally shown to be sensitive to cyclophosphamide in 1981. We have used combined laboratory and clinical investigations to demonstrate the synergy of cyclophosphamide and vincristine in the ...

Abstract	Medulloblastoma, the most common malignancy of childhood, was originally shown to be sensitive to cyclophosphamide in 1981. We have used combined laboratory and clinical investigations to demonstrate the synergy of cyclophosphamide and vincristine in the treatment of this tumor, the therapeutic gain associated with escalation of the dosage of cyclophosphamide, the consequence of and mechanisms underlying resistance of medulloblastoma to cyclophosphamide, the emerging importance of the neuraxis as a site of relapse of medulloblastoma, and newer approaches, including intrathecal 4-hydroperoxycyclophosphamide and busulfan, to treat neuraxis disease. These studies serve as a paradigm for laboratory-clinical translational research.
MeSH term(s)	Animals ; Clinical Laboratory Techniques ; Clinical Trials as Topic ; Cyclophosphamide/therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Medulloblastoma/diagnosis ; Medulloblastoma/drug therapy ; Meningeal Neoplasms/complications ; Meningeal Neoplasms/drug therapy ; Meningitis/complications ; Meningitis/drug therapy
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	1995
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/bf01052667
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