Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-proliferative activity of human interferon (HuIFN) was enhanced by dipyridamole, 2,6-bis-(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-py rimidine, when tested against various human tumor cell lines, including KT (breast carcinoma), PLC/PRF/5 (hepatoma), MGC-I, U251-SP and T98 (glioma), HAC-2 and SHIN-3 (ovarian carcinoma), and MM-ICB (melanoma). The enhancement occurred irrespective of the kind of HuIFN used (alpha, beta or gamma) and the original degree of susceptibility of the cells to HuIFN. Even low doses down to 0.01 microM of dipyridamole that had no intrinsic anti-proliferative activity could enhance the effect of HuIFN. The enhancement of HuIFN effects seems not to be caused by induction of HuIFN production, because neither anti-viral activity nor HuIFN antigens were detected in culture medium in cells treated with dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine residue, produced little enhancement of the effects of HuIFN. Among ovarian cancer cell lines tested, the enhancement of the activity of HuIFN by dipyridamole for HAC-2 and SHIN-3 cells was equivalent to or greater than that for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin derivative). However, neither HOC-21 ovarian cancer cells nor HEC-1 endometrial adenocarcinoma cells were susceptible to any combinations. When MGC-1, U251-SP, and HAC-2 cells were injected into nude mice, the growth of tumors was more markedly inhibited by the subcutaneous administration of HuIFN in combination with oral administration of dipyridamole than by the HuIFN alone. Thus, this combination therapy seems to be worth trying for human cancer, although the enhancement of the effects of HuIFN by dipyridamole varied among the cell lines examined.
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PMID:Dipyridamole enhances an anti-proliferative effect of interferon in various types of human tumor cells. 137 1

The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu-encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples.
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PMID:Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. 220 83

The in vitro and in vivo stability and anti-tumour efficacy of the anti-EGFR/anti-CD3 bispecific monoclonal antibody (biMAb), M26.1, were analysed. The interaction of the intact biMAb with Fc receptor I (Fc gamma RI) present on human leucocytes was not observed when the antibody was used as an F(ab')2 fragment. A CD8+ T-cell clone coated with M26.1 F(ab')2 was as effective as the intact biMAb in inducing IGROV1 target cell lysis when tested in a 51Cr-release assay. Variable levels of reduction of F(ab')2 to monovalent F(ab') were observed upon incubation with human ovarian cancer ascitic fluid (OCAF) or with human glioblastoma cavity fluid (GCF), but not with mouse or human sera. Activated lymphocytes coated with F(ab')2 and incubated in vitro with GCF or OCAF for 24 and 48 h respectively maintained their targeting. Thus, the F(ab')2, when present as a soluble molecule, but not when bound to T cells, might lose some functional activity as a consequence of partial reduction to F(ab'). In normal mice, M26.1 F(ab')2 retained full cytotoxic activity in the circulation, and clearance values were similar to those obtained with parental and other MAb F(ab')2. Treatment of IGROV1 tumour-bearing mice with activated human lymphocytes coated with the M26.1 F(ab')2 significantly prolonged survival of the animals compared with tumour-bearing untreated and control mice treated with lymphocytes or F(ab')2 alone. Together, these results suggest the clinical usefulness of bispecific M26.1 F(ab')2 as a targeting agent for local treatment of tumours such as glioma and ovarian cancers that express variable levels of epidermal growth factor receptor (EGFR).
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PMID:In vitro and in vivo stability and anti-tumour efficacy of an anti-EGFR/anti-CD3 F(ab')2 bispecific monoclonal antibody. 754 42

Cyclocreatine (CY), an analogue of creatine, inhibits tumor growth in vivo and proliferation of tumor cells in vitro. The goal of this study was to probe the mechanism of CY transport and cytotoxicity in C6 rat glioma cells and OC238 human ovarian carcinoma cells (creatine kinase activities of 0.16 and 0.016 units/mg protein, respectively). In both cell lines, CY significantly inhibited cell growth with no effect on membrane integrity and on the content of nucleoside triphosphates. An intrinsic 31P-nuclear magnetic resonance (31P-NMR) signal of phosphocreatine, as well as accumulation of phosphocyclocreatine (PCY) after addition of CY, was observed for C6 glioma but not for the OC238 cells. Transport of CY in C6 glioma showed Michaelis-Menten kinetics for an active sodium-dependent component. Transport was reduced more than fivefold in low-glucose medium. The toxicity of CY to C6 glioma cells may be due to PCY accumulation and cellular swelling. Another mechanism must be invoked to explain CY effects on the human ovarian cancer cells in which no PCY accumulation could be detected and no cellular swelling was observed.
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PMID:Cyclocreatine transport and cytotoxicity in rat glioma and human ovarian carcinoma cells: 31P-NMR spectroscopy. 877 41

Tamoxifen has been used most commonly to treat breast and endometrial cancer, two malignancies in which the antiestrogenic properties of tamoxifen have substantial therapeutic benefit. However, tamoxifen has been used in the treatment of other cancers as well, some in which an antiestrogen may be effective, but others in which estrogen receptor is not expressed. In estrogen receptor-negative cancers, tamoxifen has been shown to have therapeutic activity at doses approximately fourfold to eightfold above those used for estrogen receptor inhibition. It is thought that the primary mechanism of tamoxifen in estrogen-negative tumors is inhibition of protein kinase C. Clinical trials of tamoxifen in ovarian cancer, hepatocellular carcinoma, desmoid tumors, malignant glioma, pancreatic carcinoma, melanoma, and renal cell carcinoma are reviewed.
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PMID:Tamoxifen for the treatment of malignancies other than breast and endometrial carcinoma. 904 18

Oxaliplatin is a new platinum analog of the DACH family. Recent preclinical data have confirmed its non overlapping spectrum of activity with cisplatin, including acquired and intrinsic platinum resistant cell lines (as KB-CP, A 2780, HT29, CaCo2 colon cancer). When combined with other cytotoxic agents (5FU, SN38, CDDP, carboplatin), oxaliplatin has additive and/or synergistic antitumoral effects on various in vitro and in vivo models (colon, breast, ovarian and epidermoid tumors). Phase II trials have confirmed a sensorial peripherical neuropathy as its limiting toxicity while neither ototoxicity nor renal toxicities and only limited myelotoxicity were noted. Available phase II studies have established its antitumoral activity as single agent in 5FU refractory colon carcinoma while preliminary results suggest efficacy in cisplatin resistant ovarian cancer, in non small cell lung cancer, non Hodgkin lymphoma. Antitumoral activity has been observed during phases 1 in melanoma, glioma, breast and oesophageal cancers. A high response rate (28-65%) with the triple association (FU/folinic acid/oxaliplatin) has been reported in advanced colon cancer treated in first and second line settings. The results of two randomized phase III studies (FU/folinic acid +/- oxaliplatin) are expected. The oxaliplatin/cisplatin combination as salvage regimen had produced significant antitumoral activity (response rate: 45%) in resistant/refractory ovarian cancer. Finally, recent experimental and clinical data have outlined the potential interest in the development of this new original platinum compound. New single agent phases II are expected in other tumor types as well as new oxaliplatin combinations are ongoing (phase I trials of oxaliplatin/CPT-11 and of oxaliplatin/carboplatin, phase II study of oxaliplatin-vinorelbine in lung cancer.
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PMID:[Oxaliplatin: the first DACH platinum in clinical practice]. 929 71

Gene therapy using the herpes simplex virus thymidine kinase gene (HSV-TK) is a promising new approach for the treatment of gliomas, a tumor type with a poor prognosis. To limit the toxic effects of this procedure, it is desirable to restrict expression of the HSV-TK gene to the target cells. This can be accomplished by use of the promoter of the glial fibrillary acidic protein gene, an intermediate filament protein expressed primarily in astrocytes. A plasmid containing the HSV-TK gene, driven by the human glial fibrillary acidic protein promoter gfa2, was lipofected into glioma cell lines and into an ovarian cancer cell line. Treatment with ganciclovir showed efficient killing of glioma cells, with no effect on the ovarian cells. Thus, the gfa2 promoter is a promising candidate for directing expression of toxic genes to gliomas.
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PMID:Selective killing of glioma cell lines using an astrocyte-specific expression of the herpes simplex virus-thymidine kinase gene. 978 4

CD4 and one of the G-protein-coupled receptors (GPCRs) on the cell surface function as a receptor and a coreceptor, respectively, in infection of cells with human and simian immunodeficiency viruses (HIV/SIV). To determine which GPCRs can be coreceptors for HIV (HIV-1 and HIV-2) or SIV infection, several cell lines, including human osteosarcoma HOS-T4 cells and human glioma U87/CD4 cells, have been used. However, these cells often show susceptibilities to some HIV or SIV strains before transduction of GPCRs. The results of this study showed that a CD4-transduced human glioma cell line, NP-2/CD4, a human erythroleukemia cell line, K562/CD4, and a human ovarian cancer cell line, TYK/CD4, were completely resistant to the HIV-1 and HIV-2 strains tested. After transduction of several GPCRs into NP-2/CD4, K562/CD4, or TYK/CD4 cells, NP-2/CD4 cells but not K562/CD4 or TYK/CD4 cells mostly showed expected susceptibilities to several HIV strains. Therefore, an NP-2 cell system would be useful to determine the coreceptor usage of HIV isolates, to find a new coreceptor for HIV/SIV, and to analyze the early stages of HIV/SIV infection.
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PMID:Establishment of a new system for determination of coreceptor usages of HIV based on the human glioma NP-2 cell line. 1032 84

We have previously reported on mRNA expression of ERCC1, XPA and XPD in human ovarian cancer cells and tissues. Several factors can influence mRNA expression for any given gene. Alterations in gene copy number for ERCC1 and/or XPD have been reported to occur in malignant glioma specimens. Human ovarian cancer cell lines and tissues were therefore examined for evidence of altered gene copy number in selected genes within the nucleotide excision repair (NER) pathway. Six ovarian cancer cell lines were studied: A2780, A2780/CP70, SKOV3, MCAS, QvCar3 and Caov4. Cellular sensitivity to cisplatin varies by more than 1 log between some of these cells. In each of these cell lines, the genes examined included ERCC1, XPA, XPB, XPD, XPG, CSB and p53. Genomic DNA was also extracted from ovarian cancer specimens taken from 22 patients and assessed for evidence of allelic loss and/or allelic gain for ERCC1 and XPD. Twelve of the clinical specimens were from patients with platinum-sensitive tumors and ten were from patients with platinum-resistant tumors. In no case could we demonstrate a reproducible variation in gene copy number in any cell line. Among the human tissues studied, there was one case of allelic gain out of 22 specimens. We therefore conclude that alterations in gene copy number is not a common event in human ovarian cancer. Other mechanisms must be invoked to explain differences in mRNA expression for these genes.
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PMID:Absence of evidence for allelic loss or allelic gain for ERCC1 or for XPD in human ovarian cancer cells and tissues. 1073 6

Taxol has activity in the treatment of high grade gliomas but estramustine phosphate (EMP) has not been used in this setting. In vitro data demonstrates that EMP is cytotoxic to glioma cell lines and estramustine binding proteins are expressed by glioma cells. The combination of Taxol and EMP is reported to be active in the treatment of hormone-refractory prostate cancer and in taxane-resistant breast and ovarian cancer. We therefore performed a phase II study to assess the activity and toxicity of this combination in high grade gliomas. Taxol was given at a dose of 225 mg/m2 intravenously over three hours on day 1 and EMP was given at a dose of 900 mg/m2 orally on days 1 through 3. Cycles were repeated every three weeks. Twenty patients with recurrent glioblastoma multiforme (GBM) were enrolled: 11 male, median age 45 years. All patients received anti-epileptic medications and 17 (80%) had received prior chemotherapy. Of 18 evaluable patients, two had partial responses (11) and six had stable disease (33%) for a minimum of eight weeks. Treatment was well tolerated with grade 3 neutropenia occurring in only three patients. There were no other grade 3 or 4 toxicities. The median time to progression for the cohort was only six weeks (range 3-60+ weeks). The median overall survival was 12 weeks (range 3-60+ weeks). In conclusion, the combination of Taxol and EMP is well tolerated and has modest activity in the treatment of recurrent GBM.
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PMID:Phase II study of combination taxol and estramustine phosphate in the treatment of recurrent glioblastoma multiforme. 1093 Jan 1


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