Scholars@Duke
Francis Ali-Osman

Francis Ali-Osman

Margaret Harris and David Silverman Professor Emeritus of Neuro-Oncology Research
Neurosurgery, Neuro-Oncology
francis.aliosman@duke.edu
Box 3156 Med Ctr, Durham, NC 27710
199 Medical Science Research B, Durham, NC 27710

Scholarly Works - Journal articles

European genetic ancestry associated with risk of childhood ependymoma.

Journal article Neuro Oncol · November 26, 2020 BACKGROUND: Ependymoma is a histologically defined central nervous system tumor most commonly occurring in childhood. Population-level incidence differences by race/ethnicity are observed, with individuals of European ancestry at highest risk. We aimed to ... Full text Link to item Cite

Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study.

Journal article Journal of neuro-oncology · November 2019 BackgroundThe Mono-amine oxidase-A (MAO-A) enzyme is involved in the degradation and regulation of catecholamines such as serotonin, dopamine, epinephrine and nor-epinephrine. Preclinical studies suggest that this enzyme may contribute to an envir ... Full text Cite

Aspirin, NSAIDs, and Glioma Risk: Original Data from the Glioma International Case-Control Study and a Meta-analysis.

Journal article Cancer Epidemiol Biomarkers Prev · March 2019 BACKGROUND: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or NSAIDs, and results have been conflicting. The purpose of this study was to examine the associations between glioma and asp ... Full text Link to item Cite

Brain- and brain tumor-penetrating disulfiram nanoparticles: Sequence of cytotoxic events and efficacy in human glioma cell lines and intracranial xenografts.

Journal article Oncotarget · January 9, 2018 There is great interest in repurposing disulfiram (DSF), a rapidly metabolizing nontoxic drug, for brain cancers and other cancers. To overcome the instability and low therapeutic efficacy, we engineered passively-targeted DSF-nanoparticles (DSFNPs) using ... Full text Link to item Cite

Application of mutagen sensitivity assay in a glioma case-control study.

Journal article Toxicol Rep · 2018 Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in a ... Full text Link to item Cite

Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.

Journal article Nat Genet · May 2017 Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 ca ... Full text Link to item Cite

New insights into estrogenic regulation of O6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-α and MGMT proteins by fulvestrant or O6-benzylguanine indicates fresh avenues for therapy.

Journal article J Biomed Res · September 2016 Endocrine therapy using estrogen receptor-α (ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated th ... Full text Link to item Cite

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

Journal article Cancer Med · June 2016 Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse associati ... Full text Link to item Cite

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.

Journal article Cancer Epidemiol Biomarkers Prev · February 2016 BACKGROUND: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard ... Full text Link to item Cite

The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium.

Journal article Am J Epidemiol · January 15, 2016 Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospect ... Full text Link to item Cite

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells.

Journal article J Biol Chem · December 25, 2015 Under normal physiologic conditions, the glutathione S-transferase P1 (GSTP1) protein exists intracellularly as a dimer in reversible equilibrium with its monomeric subunits. In the latter form, GSTP1 binds to the mitogen-activated protein kinase, JNK, and ... 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

Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.

Journal article Sci Rep · February 5, 2015 Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametri ... Full text Link to item Cite

Germline mutations in shelterin complex genes are associated with familial glioma.

Journal article J Natl Cancer Inst · January 2015 Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two ... Full text Link to item Cite

Mitogen-activated protein kinase (MAPK) hyperactivation and enhanced NRAS expression drive acquired vemurafenib resistance in V600E BRAF melanoma cells.

Journal article J Biol Chem · October 3, 2014 Although targeting the V600E activating mutation in the BRAF gene, the most common genetic abnormality in melanoma, has shown clinical efficacy in melanoma patients, response is, invariably, short lived. To better understand mechanisms underlying this acqu ... Full text Link to item Cite

Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage.

Journal article Carcinogenesis · March 2014 The alcohol aversion drug disulfiram (DSF) reacts and conjugates with the protein-bound nucleophilic cysteines and is known to elicit anticancer effects alone or improve the efficacy of many cancer drugs. We investigated the effects of DSF on human O(6)-me ... Full text Link to item Cite

Endothelial colony forming cells (ECFCs) as a model for studying effects of low-dose ionizing radiation: growth inhibition by a single dose.

Journal article Cancer Invest · June 2013 Identification of measurable nontransient responses to low-dose radiation in human primary cell cultures remains a problem. To this end, circulating endothelial colony-forming (progenitor) cells (ECFCs) were examined as an experimental model. ECFCs were is ... Full text Link to item Cite

Correction

Journal article Cancer Science · February 2013 Full text Cite

Small ubiquitin-like modifier 1-3 conjugation [corrected] is activated in human astrocytic brain tumors and is required for glioblastoma cell survival.

Journal article Cancer Sci · January 2013 Small ubiquitin-like modifier (SUMO1-3) constitutes a group of proteins that conjugate to lysine residues of target proteins thereby modifying their activity, stability, and subcellular localization. A large number of SUMO target proteins are transcription ... Full text Link to item Cite

Abstract 2012: MAP kinase activation and suppression of anti-apoptotic Bcl-2 family members are associated with induction of apoptotic death in melanoma cells following down-regulation of glutathione S-transferase P1

Journal article Cancer Research · April 15, 2012 AbstractIntroduction. The multifunctional protein, glutathione S-transferase P1, GSTP1, is frequently overexpressed in malignant melanoma and has been associated with increased tumor growth and resistance to ... Full text Cite

Abstract 2162: EGFR-induced interaction of GSTP1 with the SH2-domain of Grb2 enhances Ras downstream activation in human glioma cells

Journal article Cancer Research · April 15, 2012 AbstractAlthough, Ras mutation are rare in human malignant gliomas, the Ras signaling pathway is frequently activated, particularly, in tumors with activated receptor tyrosine kinases, such as, epidermal gro ... Full text Cite

Associations of high-grade glioma with glioma risk alleles and histories of allergy and smoking.

Journal article Am J Epidemiol · September 1, 2011 Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility. Data from 855 high-grade glioma cases and 1,160 controls from 4 geographic regions of the United States during ... Full text Link to item Cite

Abstract 2337: Defining significance of the novel tGLI1 transcription factor in cancer growth and progression

Journal article Cancer Research · April 15, 2011 AbstractThe goal of this study is to gain a greater understanding of the molecular pathways that drive breast cancer progression and metastasis, the leading cause of breast cancer mortality. In achieving thi ... Full text Cite

Abstract 703: GSTP1 inhibition of HSP27 phosphorylation contributes to glioma drug resistance

Journal article Cancer Research · April 15, 2011 AbstractCell confluence induces resistance to chemotherapeutic agents in solid tumor cells and phosphorylation of heat shock protein 27 (HSP27), a low-weight molecular chaperon and stress response protein. H ... Full text Cite

Abstract 1635: Short hairpin RNA-mediated transcriptional suppression of glutathione S-transferase P1 suppresses growth and induces apoptosis through altered MAP kinase signaling in melanoma cells

Journal article Cancer Research · April 15, 2011 AbstractIntroduction: The glutathione-S-transferase P1 (GSTP1) protein is highly expressed in melanoma and other human cancers, and is associated with resistance to chemotherapy, aggressive tumor growth, and ... Full text Cite

EGFR and EGFRvIII undergo stress- and EGFR kinase inhibitor-induced mitochondrial translocalization: a potential mechanism of EGFR-driven antagonism of apoptosis.

Journal article Mol Cancer · March 9, 2011 BACKGROUND: Epidermal growth factor receptor (EGFR) plays an essential role in normal development, tumorigenesis and malignant biology of human cancers, and is known to undergo intracellular trafficking to subcellular organelles. Although several studies h ... Full text Link to item Cite

Assessment of type of allergy and antihistamine use in the development of glioma.

Journal article Cancer Epidemiol Biomarkers Prev · February 2011 BACKGROUND: Allergies have been associated with decreased risk of glioma; but, associations between duration and timing of allergies, and antihistamine use and glioma risk have been less consistent. The objective was to investigate this association by anal ... Full text Link to item Cite

Association between body mass index and mortality in patients with glioblastoma mutliforme.

Journal article Cancer Causes Control · December 2010 PURPOSE: To examine the association between obesity and survival in patients with glioblastoma mutliforme (GBM) METHODS: Using a prospective design, 1,259 patients with previously untreated GBM were recruited between 1991 and 2008. Height and weight were s ... Full text Link to item Cite

A Phase II trial of gemcitabine and mitoxantrone for patients with acute myeloid leukemia in first relapse.

Journal article Clin Lymphoma Myeloma Leuk · December 2010 INTRODUCTION: We evaluated the complete remission (CR) rate in patients with acute myeloid leukemia (AML) in first relapse treated with fixed-dose-rate gemcitabine and mitoxantrone. In addition, we measured multidrug resistance (MDR) proteins on pretreatme ... Full text Link to item Cite

Decoupling of DNA damage response signaling from DNA damages underlies temozolomide resistance in glioblastoma cells.

Journal article J Biomed Res · November 2010 Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults. Current therapy includes surgery, radiation and chemotherapy with temozolomide (TMZ). Major determinants of clinical response to TMZ include methylation status of the O6-me ... Full text Link to item Cite

Serine phosphorylation of glutathione S-transferase P1 (GSTP1) by PKCα enhances GSTP1-dependent cisplatin metabolism and resistance in human glioma cells.

Journal article Biochem Pharmacol · November 1, 2010 Recently, we reported that the human GSTP1 is phosphorylated and functionally activated by the PKC class of serine/threonine kinases. In this study, we investigated the contribution of this post-translational modification of GSTP1 to tumor cisplatin resist ... Full text Link to item Cite

EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity.

Journal article Cancer Lett · August 1, 2010 EGFR and its constitutively activated variant EGFRvIII are linked to glioblastoma resistance to therapy, the mechanisms underlying this association, however, are still unclear. We report that in glioblastoma, EGFR/EGFRvIII paradoxically co-expresses with p ... Full text Link to item Cite

Inhibition of poly(ADP-ribose) polymerase enhances the effect of chemotherapy in an animal model of regional therapy for the treatment of advanced extremity malignant melanoma.

Journal article Ann Surg Oncol · August 2010 BACKGROUND: Poly(ADP-ribose) polymerase (PARP) is an important regulator of programmed cell death in response to alkylating agents such as temozolomide (TMZ). The goal of this study was to determine if a systemically administered PARP-inhibitor (INO-1001) ... Full text Link to item Cite

Sorafenib, a multikinase inhibitor, enhances the response of melanoma to regional chemotherapy.

Journal article Mol Cancer Ther · July 2010 Melanoma responds poorly to standard chemotherapy due to its intrinsic chemoresistance. Multiple genetic and molecular defects, including an activating mutation in the BRaf kinase gene, are associated with melanoma, and the resulting alterations in signal ... Full text Link to item Cite

Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy.

Journal article Cancer Invest · July 2010 We present a study of the prevalence of genetic polymorphisms and expression of genes encoding the drug-resistance proteins glutathione S-transferases (GSTs) in order to gain insights into the pattern of failure evident in mantle cell lymphoma. We note a h ... Full text Link to item Cite

Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma.

Journal article Mol Cancer Ther · April 2010 In-transit metastatic melanoma, which typically presents as multifocal lesions, provides a unique setting to evaluate the utility of gene signatures for defining optimal regional therapeutic strategies and assessing the efficacy of treatment. The goal of t ... Full text Link to item Cite

Cyclooxygenase-2 is a novel transcriptional target of the nuclear EGFR-STAT3 and EGFRvIII-STAT3 signaling axes.

Journal article Mol Cancer Res · February 2010 Emerging evidence indicates a novel mode of epidermal growth factor receptor (EGFR) signaling, notably, one involves EGFR nuclear translocalization and subsequent gene activation. To date, however, the significance of the nuclear EGFR pathway in glioblasto ... Full text Link to item Cite

A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion.

Journal article Cancer Res · September 1, 2009 The family of GLI zinc finger transcription factors regulates the expression of genes involved in many important cellular processes, notably embryonal development and cellular differentiation. The glioma-associated oncogene homologue 1 (GLI1) isoform, in p ... Full text Link to item Cite

Tyrosine phosphorylation of the human glutathione S-transferase P1 by epidermal growth factor receptor.

Journal article J Biol Chem · June 19, 2009 Epidermal growth factor receptor (EGFR) gene amplification, mutations, and/or aberrant activation are frequent abnormalities in malignant gliomas and other human cancers and have been associated with an aggressive clinical course and a poor therapeutic out ... Full text Link to item Cite

Bifunctional DNA alkylator 1,3-bis(2-chloroethyl)-1-nitrosourea activates the ATR-Chk1 pathway independently of the mismatch repair pathway.

Journal article Mol Pharmacol · June 2009 The presence of DNA damage initiates signaling through the ataxia-telangiectasia mutated kinase (ATM) and the ATM- and the Rad3-related kinase (ATR), which phosphorylate, thus activating, the checkpoint kinases (Chk) 1 and 2, which leads to cell cycle arre ... Full text Link to item Cite

Association between glioma and history of allergies, asthma, and eczema: a case-control study with three groups of controls.

Journal article Cancer Epidemiol Biomarkers Prev · April 2009 Because glioma etiology is largely unknown, the inverse association of glioma risk with atopic conditions is promising and deserves close scrutiny. We examined the association between a history of allergies, asthma, and eczema, and glioma risk using siblin ... Full text Link to item Cite

Genomic and molecular profiling predicts response to temozolomide in melanoma.

Journal article Clin Cancer Res · January 15, 2009 PURPOSE: Despite objective response rates of only approximately 13%, temozolomide remains one of the most effective single chemotherapy agents against metastatic melanoma, second only to dacarbazine, the current standard of care for systemic treatment of m ... Full text Link to item Cite

Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators.

Journal article Clin Cancer Res · October 1, 2008 PURPOSE: The goals of this study are to elucidate the relationship of the oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) with glioma aggressiveness and to understand the role of high STAT3 activity in the resistan ... Full text Link to item Cite

Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma.

Journal article Clin Cancer Res · August 1, 2008 PURPOSE: A major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temo ... Full text Link to item Cite

Aberrant NF-kappaB activity is critical in focal necrosis formation of human glioblastoma by regulation of the expression of tissue factor.

Journal article Int J Oncol · July 2008 Focal necrosis is a key pathologic feature that distinguishes glioblastoma from lower grade glioma. The presence of necrosis in a glioblastoma could promote its rapid growth and clinical progression. Focal necrosis of glioblastoma seems to be associated wi ... Link to item Cite

Gene expression signatures as a guide to treatment strategies for in-transit metastatic melanoma.

Journal article J Clin Oncol · May 20, 2008 9077 Background: In an era of targeted therapeutics biopsies are increasingly used to personalize cancer treatment. The utility of a single biopsy from a melanoma patient with multifocal disease to define the characteristics of that patient's tumor is uncl ... Link to item Cite

Identification and functional characterization of the human glutathione S-transferase P1 gene as a novel transcriptional target of the p53 tumor suppressor gene.

Journal article Mol Cancer Res · May 2008 The glutathione S-transferase P1 (GSTP1) is involved in multiple cellular functions, including phase II metabolism, stress response, signaling, and apoptosis. The mechanisms underlying the significantly high GSTP1 expression in many human tumors are, howev ... Full text Link to item Cite

Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance.

Journal article Curr Opin Pharmacol · August 2007 The human glutathione S-transferase, GSTs, possess both enzymatic and non-enzymatic functions and are involved in many important cellular processes, such as, phase II metabolism, stress response, cell proliferation, apoptosis, oncogenesis, tumor progressio ... Full text Link to item Cite

Redox pathways in cancer drug discovery.

Journal article Curr Opin Pharmacol · August 2007 Full text Link to item Cite

Defining regional infusion treatment strategies for extremity melanoma: comparative analysis of melphalan and temozolomide as regional chemotherapeutic agents.

Journal article Mol Cancer Ther · May 2007 Five different human melanoma xenografts were used in a xenograft model of extremity melanoma to evaluate the variability of tumor response to regionally administered melphalan or temozolomide and to determine if various components of pertinent drug resist ... Full text Link to item Cite

Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma.

Journal article Mol Cancer Ther · October 2006 Promoter hypermethylation of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to co ... Full text Link to item Cite

Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft.

Journal article Mol Cancer Ther · September 2005 Temozolomide is a DNA-methylating agent used in the treatment of malignant gliomas. In this study, we have examined if inhibition of poly(ADP-ribose) polymerase (PARP) could increase the cytotoxicity of temozolomide, particularly in cells deficient in DNA ... Full text Link to item Cite

The human glutathione S-transferase P1 protein is phosphorylated and its metabolic function enhanced by the Ser/Thr protein kinases, cAMP-dependent protein kinase and protein kinase C, in glioblastoma cells.

Journal article Cancer Res · December 15, 2004 We report here that the human glutathione S-transferase P1 (GSTP1) protein, involved in phase II metabolism of many carcinogens and anticancer agents and in the regulation of c-Jun NH(2)-terminal kinase-mediated cell signaling, undergoes phosphorylation by ... Full text Link to item Cite

Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis.

Journal article Oncogene · April 29, 2004 The expression of matrix metalloproteinase-2 (MMP-2) has been linked with tumor invasion, angiogenesis, and metastasis. However, the molecular basis for MMP-2 overexpression in tumor cells remains unclear. In this study, by using K-1735 melanoma system, we ... Full text Link to item Cite

Glutathione S-transferase polymorphisms and survival in primary malignant glioma.

Journal article Clin Cancer Res · April 15, 2004 PURPOSE: The purpose of this research was to investigate the relationship between glutathione S-transferase (GST) polymorphisms and survival, and chemotherapy-related toxicity in 278 glioma patients. EXPERIMENTAL DESIGN: We determined genetic variants for ... Full text Link to item Cite

High-throughput detection of glutathione s-transferase polymorphic alleles in a pediatric cancer population.

Journal article Cancer Epidemiol Biomarkers Prev · February 2004 Polymorphisms of glutathione S-transferase (GST) enzymes have been correlated with altered risk of several cancers, as well as altered response and toxicity from cancer chemotherapy. We report a low cost, highly reproducible and specific PCR-based high-thr ... Full text Link to item Cite

Promoter methylation and silencing of the tissue factor pathway inhibitor-2 (TFPI-2), a gene encoding an inhibitor of matrix metalloproteinases in human glioma cells.

Journal article Oncogene · July 17, 2003 We have shown previously that the tissue factor pathway inhibitor-2 (TFPI-2), a broad range proteinase inhibitor, is highly expressed in low-grade gliomas, but, minimally expressed or undetectable in glioblastomas, and that enforced expression of this gene ... Full text Link to item Cite

Association between glutathione S-transferase p1 polymorphisms and lung cancer risk in Caucasians: a case-control study.

Journal article Lung Cancer · April 2003 Glutathione transferases (GSTs), a multiple gene family of phase II enzymes, catalyze detoxifying endogenous reactions with glutathione and protect cellular macromolecules from damage caused by cytotoxic and carcinogenic agents. Glutathione S-transferase p ... Full text Link to item Cite

Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk.

Journal article Br J Cancer · January 13, 2003 Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and ... Full text Link to item Cite

Allelic variants of the human glutathione S-transferase P1 gene confer differential cytoprotection against anticancer agents in Escherichia coli.

Journal article Pharmacogenetics · October 2002 The polymorphic human GSTP1 gene locus encodes proteins that differentially metabolize electrophilic substrates, including, many chemotherapeutic agents used in clinical cancer therapy. In this study, we used XL1-Blue MRF strain, transformed with phagemid ... Full text Link to item Cite

Cigarette smoking, glutathione-s-transferase M1 and t1 genetic polymorphisms, and breast cancer risk (United States).

Journal article Cancer Causes Control · September 2002 OBJECTIVE: It has been suggested that functional polymorphisms in genes encoding tobacco carcinogen-metabolizing enzymes may modify the relationship between tobacco smoking and breast cancer risk. We sought to determine if there is a gene-environment inter ... Full text Link to item Cite

The DNA repair protein, O(6)-methylguanine-DNA methyltransferase is a proteolytic target for the E6 human papillomavirus oncoprotein.

Journal article Oncogene · August 29, 2002 We have previously shown that O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein that protects tissues against toxic and carcinogenic effects of alkylating agents, is degraded through ubiquitination-dependent proteolysis. Here, we invest ... Full text Link to item Cite

Phosphorylation of O6-alkylguanine-DNA alkyltransferase: experience with a GST-fusion protein and a new pull-down assay.

Journal article Cancer Lett · July 8, 2002 We showed recently that human O6-alkylguanine-DNA alkyltransferase (AGT), a key target for enhancing the efficacy of anticancer alkylating agents, is regulated by phosphorylation in brain tumor cells. This report describes the problems we encountered in us ... Full text Link to item Cite

Mechanisms of resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea in human medulloblastoma and rhabdomyosarcoma.

Journal article Mol Cancer Ther · July 2002 Medulloblastoma (D-341 MED) and rhabdomyosarcoma (TE-671) cell lines, which are resistant to either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or the combination of BCNU and O6-benzylguanine (O6-BG), were generated by serial escalation of BCNU. The activi ... Link to item Cite

Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA.

Journal article Oncogene · January 31, 2002 The human Dkk-1 (hDkk-1) gene, a transcriptional target of the p53 tumor suppressor, encodes a powerful inhibitor of the Wnt signaling pathway and regulates the spatial patterning/morphogenesis of the mammalian central nervous system. We investigated the p ... Full text Link to item Cite

Minimal and inducible regulation of tissue factor pathway inhibitor-2 in human gliomas.

Journal article Oncogene · January 31, 2002 Tissue factor pathway inhibitor-2 (TFPI-2), a serine protease inhibitor abundant in the extra cellular matrix, is highly expressed in non-invasive cells but undetectable levels in highly invasive human glioma cells. The mechanisms responsible for its trans ... Full text Link to item Cite

Cyclic AMP mediated GSTP1 gene activation in tumor cells involves the interaction of activated CREB-1 with the GSTP1 CRE: a novel mechanism of cellular GSTP1 gene regulation.

Journal article J Cell Biochem · 2002 The human GSTP1 gene is frequently over-expressed in many human cancers and the expression increases with tumor progression and is associated with a more aggressive biology, poor patient survival, and resistance to therapy. The molecular regulation of the ... Full text Link to item Cite

Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells.

Journal article Oncogene · June 21, 2001 Increases in abundance of cathepsin B transcript and protein correlate with increases in tumor grade and alterations in subcellular localization and activity of cathepsin B. The enzyme is able to degrade the components of the extracellular matrix (ECM) and ... Full text Link to item Cite

Enforced expression of wild-type p53 curtails the transcription of the O(6)-methylguanine-DNA methyltransferase gene in human tumor cells and enhances their sensitivity to alkylating agents.

Journal article Clin Cancer Res · May 2001 We used isogenic human tumor cell lines to investigate the specific and direct effects of wild-type (wt) p53 on the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein that confers tumor resistance to many anticancer alkylat ... Link to item Cite

Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines.

Journal article Clin Cancer Res · April 2001 The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in the proteolytic cascade involved in the metastasis of lung and other cancers. We report that the reduction in uPAR levels produced by an antisense strategy usi ... Link to item Cite

The human glutathione S-transferase P1 (GSTP1) gene is transactivated by cyclic AMP (cAMP) via a cAMP response element (CRE) proximal to the transcription start site

Journal article Chemico Biological Interactions · February 28, 2001 The human GSTP1 gene is frequently up-regulated in human malignancies and is associated with resistance to chemotherapy and an aggressive biology. Presently, however, the molecular mechanisms involved in the regulation of this gene are not well understood. ... Cite

Genetic polymorphism at the glutathione S-transferase (GST) P1 locus is a breast cancer risk modifier.

Journal article Int J Cancer · February 1, 2001 The isolation of full-length cDNAs of naturally occurring GSTP1 gene variants, and the demonstration that these alleles are distributed in the normal population, have provided conclusive evidence that the human GSTP1 gene locus is polymorphic and that spec ... Full text Link to item Cite

Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion.

Journal article Cancer Res · December 15, 2000 Increased expression of matrix metalloproteinases (MMPs) has been associated with human glioblastoma tumor progression. In this study, we sought to down-regulate MMP-9 expression by stably transfecting a high-grade glioblastoma cell line with a plasmid vec ... Link to item Cite

Effects of radiation on the levels of MMP-2, MMP-9 and TIMP-1 during morphogenic glial-endothelial cell interactions.

Journal article Int J Cancer · December 1, 2000 Radiation-induced damage to the central nervous system (CNS) is believed to target glial or endothelial cells or both, although the pathophysiology of the process is poorly understood. We therefore used a coculture system, in which glioblastoma SNB19 cells ... Full text Link to item Cite

DNA repair protein O6-alkylguanine-DNA alkyltransferase is phosphorylated by two distinct and novel protein kinases in human brain tumour cells.

Journal article Biochem J · October 15, 2000 We showed recently that human O(6)-alkylguanine-DNA alkyltransferase (AGT), an important target for improving cancer chemotherapy, is a phosphoprotein and that phosphorylation inhibits its activity [Srivenugopal, Mullapudi, Shou, Hazra and Ali-Osman (2000) ... Link to item Cite

Glutathione S-transferase GSTP1 and cyclin D1 genotypes: association with numbers of basal cell carcinomas in a patient subgroup at high-risk of multiple tumours.

Journal article Pharmacogenetics · August 2000 We previously described associations between basal cell carcinoma (BCC) numbers and allelic variants at loci that mediate host response to ultraviolet radiation (UV). These associations were largely exerted in cases with the multiple presentation phenotype ... Full text Link to item Cite

DNA methyltransferase levels and altered CpG methylation in the total genome and in the GSTP1 gene in human glioma cells transfected with sense and antisense DNA methyltransferase cDNA.

Journal article J Cell Biochem · April 2000 This study examines the efficacy of using plasmid expression vectors containing sense and antisense DNA MTase cDNA to both up- and downregulate intracellular DNA MTase levels in human glioma cells. The effects of the changes in MTase levels on global genom ... Link to item Cite

Protein phosphorylation is a regulatory mechanism for O6-alkylguanine-DNA alkyltransferase in human brain tumor cells.

Journal article Cancer Res · January 15, 2000 The biochemical regulation of human O6-alkylguanine-DNA alkyltransferase (AGT), which determines the susceptibility of normal tissues to methylating carcinogens and resistance of tumor cells to many alkylating agents, is poorly understood. We investigated ... Link to item Cite

Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascades.

Journal article Clin Exp Metastasis · 2000 Our previous studies have shown that MMP-9 levels are significantly elevated during the progression of human gliomas. In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invas ... Full text Link to item Cite

Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions.

Journal article Clin Exp Metastasis · 2000 The purpose of this study was to investigate the roles of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the formation of capillary structures by human brain microvascular endothelial cells cocultured with SNB19 ... Full text Link to item Cite

Amplification of telomeric DNA directly correlates with metastatic potential of human and murine cancers of various histological origin.

Journal article Int J Oncol · September 1999 Telomeres, repeated DNA sequences (T2AG3)n that guard the ends of chromosomes, serve as a checkpoint for cell-cycle progression and regulate cell senescence and apoptosis. Loss of the telomeric repeats promotes genomic instability, which is the hallmark of ... Full text Link to item Cite

In vitro repair synthesis of BCNU-induced DNA damage.

Journal article Cancer Biochem Biophys · October 1998 The nitrosoureas including BCNU are potent chemotherapeutic drugs and have been used extensively for treatment of brain tumors and other neoplasias but the mechanisms of action for the DNA lesions created and their repair are still unclear. We have recentl ... Link to item Cite

Translational inhibition of messenger RNA of the human pi class glutathione S-transferase by antisense oligodeoxyribonucleotides.

Journal article Chem Biol Interact · April 24, 1998 In this study, a T7 plasmid expression vector containing the cDNA of a variant human GST-pi gene, hGSTP1*C, was used to examine the translational inhibition of the GST-pi mRNA with antisense deoxyribonucleotides (AS-ONs), and to investigate the dependency ... Full text Link to item Cite

Structure of the human allelic glutathione S-transferase-pi gene variant, hGSTP1 C, cloned from a glioblastoma multiforme cell line.

Journal article Chem Biol Interact · April 24, 1998 We recently reported the cloning of full-length cDNAs corresponding to mRNAs of three GST-pi genes, hGSTP1*A, hGSTP1*B and hGSTP1*C, as well as, the isolation of the full-length hGSTP1*C, of the human glutathione S-transferase-pi (GST-pi) gene that is char ... Full text Link to item Cite

Nitric oxide and neopterin levels and clinical response in stage III melanoma patients receiving concurrent biochemotherapy.

Journal article Melanoma Res · April 1998 The combination of cisplatin-based chemotherapy with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), referred to as biochemotherapy, has produced overall response rates of greater than 50% in advanced melanoma patients, with durable complete respons ... Full text Link to item Cite

DNA damage in peripheral blood mononuclear cells correlates with response to biochemotherapy in melanoma.

Journal article Melanoma Res · April 1998 The combination of cisplatin-based chemotherapy with interleukin-2 (IL-2) and interferon, referred to as biochemotherapy, has shown encouraging results in patients with advanced melanoma. Toxicity is high, however and no objective parameters exist to disti ... Full text Link to item Cite

Genomic cloning of hGSTP1*C, an allelic human Pi class glutathione S-transferase gene variant and functional characterization of its retinoic acid response elements.

Journal article J Biol Chem · December 26, 1997 The complete hGSTP1*C, consisting of 7 exons and 6 introns contained in 3116 base pairs, was isolated from a cosmid genomic library of a glioblastoma multiforme cell line. Although the promoter of hGSTP1*C was identical to that of the previously reported G ... Full text Link to item Cite

Prognostic significance of glutathione S-transferase pi expression and subcellular localization in human gliomas.

Journal article Clin Cancer Res · December 1997 The glutathione S-transferase (GST)-pi gene is overexpressed in many human cancers and preneoplastic lesions and is associated with failure of cancer chemotherapy and poor patient survival. Although GST-pi overexpression in tumors of the central nervous sy ... Link to item Cite

Prognostic significance of glutathione S-transferase π expression and subcellular localization in human gliomas

Journal article Clinical Cancer Research · December 1, 1997 The glutathione S-transferase (GST)-Ï€ gene is overexpressed in many human cancers and preneoplastic lesions and is associated with failure of cancer chemotherapy and poor patient survival. Although GST-Ï€ overexpression in tumors of the central nervous syst ... Cite

Activity and distribution of the cysteine prodrug activating enzyme, 5-oxo-L-prolinase, in human normal and tumor tissues.

Journal article Cancer Lett · July 15, 1997 5-Oxo-L-prolinase (OPase), a key enzyme of the gamma-glutamyl cycle, has the ability to metabolize L-2-oxothiazolidine-4-carboxylic acid (OTC) to cysteine, and thereby increase intracellular glutathione (GSH) levels. This strategy of GSH elevation can be p ... Full text Link to item Cite

Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.

Journal article Cancer Res · July 15, 1997 A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-me ... Link to item Cite

Effect of cisplatin and BCNU on MMP-2 levels in human glioblastoma cell lines in vitro.

Journal article Clin Exp Metastasis · July 1997 Matrix metalloproteinases (MMPs) play an important role in various physiological and pathological conditions such as tissue remodeling, and cancer cell invasion and metastasis. The aim of this study was to determine the effect of the antitumor compounds ci ... Full text Link to item Cite

Cisplatin but not BCNU inhibits urokinase-type plasminogen activator levels in human glioblastoma cell lines in vitro.

Journal article Clin Exp Metastasis · July 1997 Glioblastomas extensively invade the surrounding normal brain tissue, with a concomitant expression of various proteolytic enzymes, in particular urokinase-type plasminogen activator (uPA). In this study we used cis-diamminedichloroplatinum (cisplatin) and ... Full text Link to item Cite

Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins.

Journal article J Biol Chem · April 11, 1997 We report the isolation of three full-length cDNAs corresponding to the mRNAs of closely related glutathione S-transferase (GST) Pi genes, designated hGSTP1*A, hGSTP1*B, and hGSTP1*C, expressed in normal cells and malignant gliomas. The variant cDNAs resul ... Full text Link to item Cite

Detection of DNA damage in transcriptionally active genes by RT-PCR and assessment of repair of cisplatin-induced damage in the glutathione S-transferase-pi gene in human glioblastoma cells.

Journal article Toxicol Appl Pharmacol · March 1997 Cisplatin is an anticancer agent frequently used as an alternative to the nitrosoureas in brain tumor chemotherapy. We describe the use of a technique of quantitative reverse transcription-polymerase chain reaction (RT-PCR) to examine the damage induced in ... Full text Link to item Cite

Characterization of the mechanisms of busulfan resistance in a human glioblastoma multiforme xenograft.

Journal article Cancer Chemother Pharmacol · 1997 Busulfan is an alkylating agent commonly used in the treatment of chronic myelogenous leukemia and in combination with cyclophosphamide in preparation for allogeneic bone marrow transplantation. Serial treatment of a childhood high-grade glioma xenograft ( ... Full text Link to item Cite

Coordinate up-regulation of cyclin-dependent kinase 4 and its inhibitor p16INK4 in human glioma cells following chloroethylnitrosourea-induced DNA damage

Journal article International Journal of Oncology · January 1, 1997 Anomalies in the genes of the cell cycle regulators, p16INK4 and CDK4 are highly frequent in human gliomas and other cancers, however, the extent to which these defects are involved in regulating the response of tumor cells to DNA damaging agent ... Full text Cite

Buthionine sulfoximine induction of gamma-L-glutamyl-L-cysteine synthetase gene expression, kinetics of glutathione depletion and resynthesis, and modulation of carmustine-induced DNA-DNA cross-linking and cytotoxicity in human glioma cells.

Journal article Mol Pharmacol · June 1996 Glutathione (GSH) depletion by buthioninine sulfoximine (BSO) is being explored clinically as a means of enhancing the efficacy of cancer chemotherapy. We investigated the kinetics of GSH depletion and altered gamma-L-glutamyl-L-cysteine synthetase (gamma- ... Link to item Cite

Deletions and rearrangements inactivate the p16INK4 gene in human glioma cells.

Journal article Oncogene · May 2, 1996 Structural alterations in the p16INK4 gene were examined in early passage human glioma cell lines and related to the expression of p16 transcripts and protein. Using the Southern blot approach, we observed both homozygous and hemizygous deletions, as well ... Link to item Cite

Ubiquitination-dependent proteolysis of O6-methylguanine-DNA methyltransferase in human and murine tumor cells following inactivation with O6-benzylguanine or 1,3-bis(2-chloroethyl)-1-nitrosourea.

Journal article Biochemistry · January 30, 1996 In this study, we investigated the role of ubiquitination in the disposition of the inactivated O6-methylguanine-DNA methyltransferase (MGMT) protein in human (HT-29 and CEM) and murine (ts85) tumor cells. Using a combination of immunoprecipitation and imm ... Full text Link to item Cite

Repair analysis of 4-hydroperoxycyclophosphamide-induced DNA interstrand crosslinking in the c-myc gene in 4-hydroperoxycyclophosphamide-sensitive and -resistant medulloblastoma cell lines.

Journal article Cancer Chemother Pharmacol · 1996 Cyclophosphamide is one of the most active agents in the treatment of medulloblastoma. However, development of resistance to this alkylator frequently occurs and is the harbinger of tumor progression and death. In order to understand the biochemical basis ... Full text Link to item Cite

Enhancement of melphalan activity by inhibition of DNA polymerase-alpha and DNA polymerase-beta.

Journal article Cancer Chemother Pharmacol · 1996 Our previous studies exploring melphalan resistance in the human rhabdomyosarcoma xenograft TE-671 MR revealed elevation of DNA polymerase-alpha and DNA polymerase-beta. The present study evaluated the alteration of melphalan activity in TE-671 (melphalan- ... Full text Link to item Cite

Culture of human normal brain and malignant brain tumors for cellular, molecular, and pharmacological studies.

Journal article Methods Mol Med · 1996 Human brain neoplasms comprise a highly heterogeneous and biologically diverse group of tumors, the most common and most malignant of which are those of neuroepithelial origin (1) Despite intensive research, little is still understood about the cellular an ... Full text Link to item Cite

Simultaneous amplification of four DNA repair genes and beta-actin in human lymphocytes by multiplex reverse transcriptase-PCR.

Journal article Cancer Res · November 1, 1995 We describe here the development, optimization, and use of a non-radioactive, quantitative, multiplex reverse transcriptase-PCR technique to measure, in a single reaction, the relative levels of the transcripts of four DNA repair genes (XPCC, hMSH2, XRCC1, ... Link to item Cite

Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates.

Journal article Radiother Oncol · June 1995 L-Homocysteine thiolactone (L-HCTL) was evaluated for its potential as an intravenously-administered central nervous system (CNS) radioprotector in C3H mice and F344 rats. Toxicity assessments in the mouse yielded a LD50 of 297 mg/kg and in the rat 389 mg/ ... Full text Link to item Cite

Identification of a brain- and reproductive-organs-specific gene responsive to DNA damage and retinoic acid.

Journal article Biochem Biophys Res Commun · January 17, 1995 We have identified and sequenced a new gene from human cells that is responsive to DNA damage and retinoic acid treatment, and it is highly expressed in brain and reproductive organs (BRE). This BRE gene encodes an mRNA of 1.7-1.9 kb, with an open reading ... Full text Link to item Cite

Suppression of antiproliferative effects of tumor necrosis factor by transfection of cells with human platelet-derived growth factor B/c-sis gene.

Journal article FEBS Lett · January 2, 1995 The growth of cells is determined by the balance between growth-stimulatory and growth-inhibitory signals. In the present study, we demonstrate that the transfection of NIH 3T3 cells with a platelet-derived growth factor (PDGF-Blc-sis) gene induces resista ... Full text Link to item Cite

Formation and repair of 1,3-bis-(2-chloroethyl)-1-nitrosourea and cisplatin induced total genomic DNA interstrand crosslinks in human glioma cells.

Journal article Cancer Biochem Biophys · January 1995 The kinetics of formation and repair of total genomic DNA interstrand crosslinks (ISCs) induced by BCNU and cis-DDP were studied in cells of 6 human malignant gliomas and related with their degree of drug resistance. DNA ISCs were formed rapidly (peak 6-12 ... Link to item Cite

Transfection of cells with transforming growth factor-alpha leads to cellular resistance to the antiproliferative effects of tumor necrosis factor.

Journal article FEBS Lett · October 31, 1994 Tumor necrosis factor (TNF) is a growth-modulatory cytokine that inhibits the growth of certain cell lines, stimulates the growth of some, and has no effect on the growth of still others. The molecular basis for this differential regulation of growth by TN ... Full text Link to item Cite

Mechanism of the anti-tumour effect of biochemotherapy in melanoma: preliminary results.

Journal article Melanoma Res · October 1994 During the conduct of a biochemotherapy trial in which cisplatin, vinblastine and dacarbazine (CVD) were administered concurrently with interleukin-2 (IL-2) plus interferon-alpha 2a (IFN-alpha 2a) (biochemotherapy) in advanced melanoma, we performed a seri ... Full text Link to item Cite

Correlation of total and interstrand DNA adducts in tumor and kidney with antitumor efficacies and differential nephrotoxicities of cis-ammine/cyclohexylamine-dichloroplatinum(II) and cisplatin.

Journal article Biochem Pharmacol · August 17, 1994 Mixed amine platinum complexes have been identified as a new class of antitumor agents with activity in some cisplatin-resistant tumor models. cis-Ammine/cyclohexylamine-dichloroplatinum(II) is one such analog that we have evaluated in vivo and found it to ... Full text Link to item Cite

Elevated DNA polymerase alpha, DNA polymerase beta, and DNA topoisomerase II in a melphalan-resistant rhabdomyosarcoma xenograft that is cross-resistant to nitrosoureas and topotecan.

Journal article Cancer Res · July 1, 1994 Previous investigations have revealed that the human TE-671 MR human rhabdomyosarcoma xenograft selected in vivo for melphalan resistance (M. C. Rosenberg, et al., Cancer Res., 49: 6917-6922, 1989) is cross-resistant to a wide variety of alkylating agents ... Link to item Cite

pp60v-src kinase overexpression leads to cellular resistance to the antiproliferative effects of tumor necrosis factor.

Journal article FEBS Lett · May 30, 1994 While some tumor cells are sensitive to the antiproliferative effects of tumor necrosis factor (TNF), others are resistant. The molecular basis for cellular resistance to TNF is not completely understood. Previously we have shown that transfection of cells ... Full text Link to item Cite

Cell density-dependent regulation of cell surface expression of two types of human tumor necrosis factor receptors and its effect on cellular response.

Journal article J Cell Biochem · April 1994 Tumor necrosis factor (TNF) is a multipotential cytokine known to regulate the growth of a wide variety of normal and tumor cells. It has been shown that the density of cells in culture can modulate the growth regulatory activities of TNF, the mechanism of ... Full text Link to item Cite

Induction of tissue-type plasminogen activator and 72-kDa type-IV collagenase by ionizing radiation in rat astrocytes.

Journal article Int J Cancer · January 15, 1994 Radiation-induced damage in the central nervous system (CNS) is believed to be targeted to glial or endothelial cells or both, although the pathophysiology of the process is still poorly understood. In this study, we irradiated rat astrocytes with single d ... Full text Link to item Cite

Role of plasminogen activator and of 92-KDa type IV collagenase in glioblastoma invasion using an in vitro matrigel model.

Journal article J Neurooncol · 1994 The invasive nature of human gliomas represents a major factor in preventing their total resection. The exact nature of the underlying mechanisms of tumor cell invasion are still unclear. In this study, we have quantitatively assayed a glioblastoma cell li ... Full text Link to item Cite

Enhanced repair of a cisplatin-damaged reporter chloramphenicol-O-acetyltransferase gene and altered activities of DNA polymerases alpha and beta, and DNA ligase in cells of a human malignant glioma following in vivo cisplatin therapy.

Journal article J Cell Biochem · January 1994 Current evidence suggest an important role for increased repair of drug-induced DNA damage as one of the major mechanisms involved in tumor cell resistance to cis-DDP. In this study, we examined the DNA repair capacity and the activities of three DNA repai ... Full text Link to item Cite

Topoisomerase II inhibition and altered kinetics of formation and repair of nitrosourea and cisplatin-induced DNA interstrand cross-links and cytotoxicity in human glioblastoma cells.

Journal article Cancer Res · December 1, 1993 By altering the accessibility of DNA sequences for alkylation or platination, and/or for subsequent repair, topoisomerase II can potentially affect the level of DNA interstrand cross-links induced in cells by bifunctional agents. In this study, we investig ... Link to item Cite

Glutathione-associated cis-diamminedichloroplatinum(II) metabolism and ATP-dependent efflux from leukemia cells. Molecular characterization of glutathione-platinum complex and its biological significance.

Journal article J Biol Chem · September 25, 1993 Accumulating evidence suggests a critical role of intracellular glutathione in tumor cell resistance to alkylating agents. The present study provides evidence for the direct interaction between cis-diamminedichloroplatinum(II) (cisplatin) and glutathione ( ... Link to item Cite

Modulation of in vitro invasion of human glioblastoma cells by urokinase-type plasminogen activator receptor antibody.

Journal article Cancer Res · September 15, 1993 Four human glioblastoma cell lines (U251, UWR1, UWR2, and UWR3) were tested for the expression of the cell surface receptor for urokinase-type plasminogen activator (uPA). To our knowledge there have been no previous reports about the uPA receptors (uPARs) ... Link to item Cite

Purification and biochemical characterization of gamma-glutamylcysteine synthetase from a human malignant astrocytoma cell line.

Journal article Biochem Mol Biol Int · August 1993 gamma-Glutamylcysteine synthetase (EC 6.3.2.2.) the key regulatory enzyme in glutathione biosynthesis was purified from a human malignant astrocytoma cell line using a combination of ammonium sulfate fractionation, DE-52 cellulose chromatography and ATP-ag ... Link to item Cite

Pituitary oncocytomas: clinical features, characteristics in cell culture, and treatment recommendations.

Journal article J Neurooncol · April 1993 To determine whether there are significant differences between oncocytomas and pituitary adenomas, we evaluated clinical features, treatment regimens and outcome in 23 males and 9 females (average age 64 years, range 43-81 years) with the histologic diagno ... Full text Link to item Cite

Development of lipophilic anticancer agents for the treatment of brain tumors by the esterification of water-soluble chlorambucil.

Journal article Clin Exp Metastasis · March 1993 The lipophilic derivatives of the anticancer alkylating agent chlorambucil, chlorambucil-methyl, -isopropyl and -tertiary butyl esters, were synthesized and administered i.v. to anesthetized rats. Plasma and brain concentrations of these agents and of thei ... Full text Link to item Cite

Phase II evaluation of high-dose intravenous cisplatin for treatment of adult malignant gliomas recurrent after chloroethylnitrosourea failure.

Journal article J Neurooncol · February 1992 Twenty-one patients with recurrent malignant glioma who had failed prior chemotherapy with nitrosoureas were treated with high-dose intravenous cisplatin on days 1 and 8 of successive 4 week cycles. Fourteen patients were evaluable for response. Four patie ... Full text Link to item Cite

Induction of transformational changes in normal endothelial cells by cultured human astrocytoma cells.

Journal article J Neurosurg · October 1991 Endothelial cell proliferation is a significant biological feature of malignant astrocytomas. The ability of the cells of these tumors to elaborate mitogenic angiogenesis factors has been well documented. However, less is known about the transformational e ... Full text Link to item Cite

Isolation and characterization of microvessels from normal brain and brain tumors.

Journal article J Neurooncol · August 1991 We describe a new technique for isolating microvessels from both brain and brain tumors. This method is relatively quick and provides a microvessel preparation free of contamination by other brain tissue. Using this method, structurally intact microvessels ... Full text Link to item Cite

Glutathione content and glutathione-S-transferase expression in 1,3-bis(2-chloroethyl)-1-nitrosourea-resistant human malignant astrocytoma cell lines.

Journal article Cancer Res · November 1, 1990 gamma-L-glutamyl-L-cysteinylglycine (GSH) has been shown to inactivate 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and quench DNA crosslink precursors of BCNU. Because of the central role of 2-chloroethyl-nitrosoureas in brain tumor chemotherapy, we invest ... Link to item Cite

Stimulation and inhibition of 1,3-bis(2-chloroethyl)-1-nitrosourea-induced strand breaks and interstrand cross-linking in Col E1 plasmid deoxyribonucleic acid by polyamines and inorganic cations.

Journal article Biochem Pharmacol · August 1, 1990 The influence of various polyamines and metallic cations on 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced DNA single-strand breaks and DNA interstrand cross-linking was in Col E1 plasmid using electrophoretic techniques. Spermidine and spermine (0.4 ... Full text Link to item Cite

S1-nuclease enhancement of the ethidium bromide binding assay of drug-induced DNA interstrand crosslinking in human brain tumor cells.

Journal article Anal Biochem · June 1990 A modification, using S1-nuclease, of a simple and sensitive fluorometric assay with ethidium bromide was developed for the measurement of cellular DNA interstrand crosslinking induced by bifunctional alkylators. Cells are lysed and treated with proteinase ... Full text Link to item Cite

DNA interstrand crosslinking and strand break repair in human glioma cell lines of varying [1,3-bis(2-chloroethyl)-1-nitrosourea] resistance.

Journal article Anticancer Res · 1990 The production of DNA interstrand crosslinks (ISC) by BCNU and other bifunctional alkylators and the effects of these drugs on the repair of radiation-induced DNA-single strand breaks (SSB) were studied in two human glioblastoma used to assess both DNA-ISC ... Link to item Cite

Extracellular potassium influences DNA and protein syntheses and glial fibrillary acidic protein expression in cultured glial cells.

Journal article Glia · 1990 Previous reports of increases in glial cell number and expression of glial fibrillary acidic protein (GFAP) in stimulated brain regions or epileptic tissue have implicated a role for increases in extracellular potassium concentration ([K+]o) in glial react ... Full text Link to item Cite

Decreased DNA interstrand cross-linking and cytotoxicity induced in human brain tumor cells by 1,3-bis(2-chloroethyl)-1-nitrosourea after in vitro reaction with glutathione.

Journal article Cancer Res · November 1, 1989 Although both direct and glutathione S-transferase (GST)-catalyzed interactions between many electrophiles and GSH generally result in inactivation of the former, there are several reports of compounds whose electrophilic, alkylating, and cytotoxic activit ... Link to item Cite

Quenching of DNA cross-link precursors of chloroethylnitrosoureas and attenuation of DNA interstrand cross-linking by glutathione.

Journal article Cancer Res · October 1, 1989 Interstrand DNA cross-linking is essential for the antitumor activity of chloroethylnitrosoureas (CENUs). The critical cross-links have been proposed to involve a rapid O6-guanine chloroethylation on one DNA strand, followed by a rearrangement of the O6-(2 ... Link to item Cite

Optimization and characterization of the capillary human tumor clonogenic cell assay.

Journal article Cancer Res · February 1, 1988 The capillary human tumor clonogenic cell assay (HTCA) has been shown to have important advantages over conventional HTCAs. In the present report, this promising novel HTCA was further optimized and characterized using 46 primary human tumor specimens, 6 h ... Link to item Cite

Application of in vivo and in vitro pharmacokinetics for physiologically relevant drug exposure in a human tumor clonogenic cell assay.

Journal article Cancer Res · July 15, 1987 The biological half-lives and decay rate constants under the conditions of a human brain tumor clonogenic cell assay were determined for six clinically used anticancer agents. The agents studied were: 1,3-bis(2-chloroethyl)-1-nitrosourea; 3-(2-chloroethyl- ... Link to item Cite

Rapid method for permanent slide preparation of colonies in soft agar cultures.

Journal article Int J Cell Cloning · September 1986 A method is presented for preparing permanent microscopic slides from colony-bearing agar layers in soft agar cultures. The main advantages of this technique are its simplicity, rapidity and accurate colony preservation. This method could have broad applic ... Full text Link to item Cite

Relationship between histopathology and in vitro clonogenicity in breast cancer.

Journal article Breast Cancer Res Treat · 1986 The human tumor clonogenic assay was used to culture 268 primary and metastatic breast cancer samples. Cultures of 181 specimens were prepared in the double-layer agar system and 87 in a modified system utilizing a liquid upper layer. Successful growth (gr ... Full text Link to item Cite

Chemical structure of carbamoylating groups and their relationship to bone marrow toxicity and antiglioma activity of bifunctionally alkylating and carbamoylating nitrosoureas.

Journal article Cancer Res · September 1985 Although the antitumor effects of chloroethylnitrosoureas have been shown to be due primarily to DNA-DNA cross-linking by the alkylating moieties of these agents, the basis of the often accompanying bone marrow toxicity has been more controversial. We repo ... Link to item Cite

Potential antiglioma activity of 9-hydroxy-2-N-methylellipticine as determined by pharmacological and human tumor clonogenic cell studies.

Journal article Cancer Res · July 1985 The antiglioma activity of elliptinium (HME) was investigated in a human glioma clonogenic cell assay. Early passage cells of three human glioma cell lines (SF126, SF375, and SF407) were exposed to HME at the clinically achievable dose of 3 microM for 3 h. ... Link to item Cite

In vitro and in vivo investigations for the development of cytostatic methylhydrazones.

Journal article J Cancer Res Clin Oncol · 1985 In in vitro short-term (3 h) assays, the beta-chloroethyl-methyl-hydrazones B 1 and B 2 inhibit the uptake of 3H-thymidine by EAC and L 1210 leukemia cells, B 2 being 5 to 10 times more effective than B 1. The growth inhibitory effect of both compounds was ... Full text Link to item Cite

Reculturing of cells from primary CFU-C colonies.

Journal article Z Naturforsch C Biosci · 1985 This study was aimed at investigating whether cells of CFU-C derived colonies could form secondary colonies. Bone marrow cultures of volumes of agar medium between 25 microliter and 75 microliter contained in glass capillaries were stimulated with mouse lu ... Link to item Cite

In vitro bone marrow cytotoxicity of nitrosoureas: Possible role for carbamoylation

Journal article Proceedings of the American Association for Cancer Research · January 1, 1985 Cite

Use of quinones in brain-tumor therapy: preliminary results of preclinical laboratory investigations.

Journal article J Toxicol Environ Health · 1985 Failure of current chemotherapeutic agents to effectively treat human brain tumors has prompted the search for alternative regimens based on the inherent metabolic pathways of target cells. One way to accomplish this goal would be to design drugs in an ina ... Full text Link to item Cite

Cytoprotection by somatostatin of normal and malignant clonogenic cells against the in vitro cytotoxicity of bischloroethylnitrosourea (BCNU).

Journal article Arzneimittelforschung · 1984 The various pharmacological effects of somatostatin may be explained by the hypothesis that the paracrine peptide, by "stabilizing" cell membranes, inhibits the secretion of hormones as well as protects other cells (vascular endothelium, parenchyma) from d ... Link to item Cite

Correlation of intralesional in vivo chemotherapy of line 10 hepatoma with in vitro drug sensitivity.

Journal article Int J Cell Cloning · June 1983 The effects of intralesional chemotherapy with 7 different drugs on line 10 hepatoma grown in strain 2 guinea pigs were compared with the sensitivity of line 10 tumor cells in vitro, using a micro modification of the tumor stem assay with capillary tubes. ... Full text Link to item Cite

Stimulation of clonal tumor cell growth in vitro by inhibiting the serum polyamine oxidase activity.

Journal article J Cancer Res Clin Oncol · 1983 Several tumors are characterized by elevated levels of polyamines involved in vital cell proliferation processes. Polyamine oxidases (PAO), present in ruminant and particularily in fetal calf serum (FCS), degrade polyamines to polyaminoaldehydes and other ... Full text Link to item Cite

Two different types of granulocyte colony-stimulating factor produced by bovine lung tissue.

Journal article Blut · January 1982 Bovine lung tissue produces two different types of granulocyte colony-stimulating factor (CSF). The high molecular weight (MW) type (CSF-F) of 70,000 d by Sephadex G-100 gel filtration is only found in conditioned medium of homogenized tissue incubated in ... Full text Link to item Cite

Comparison of cytostatic sensitivities of L 1210 cells and human stimulated lymphocytes in three cell proliferation assays.

Journal article J Cancer Res Clin Oncol · 1980 Three methods of measuring cell proliferation, viz., cellular H-thymidine uptake, counting of cells in suspension, and counting of colonies of cells grown in agar contained in glass capillaries, were compared by studying cell growth kinetics using the L 12 ... Full text Link to item Cite