Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.
Eur J Cancer 1992
PMID:Phase II study of tauromustine in malignant glioma. 141 89

alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme ornithine decarboxylase, inhibits the growth of brain tumor cell lines and is undergoing clinical trials as a treatment for brain tumors. Platelet-derived growth factor (PDGF) is thought to regulate the growth and development of precursors of both normal and neoplastic astrocytic cells; calcium signaling is thought to play a role in the transduction of PDGF signals. Using laser fluorescence image cytometry, flow cytometry, and spectrofluorometry, we studied the effect of DFMO on the calcium signals induced by PDGF in A172 human glioblastoma cells. Four days of treatment with 5 mM DFMO substantially shortened PDGF-induced calcium signals. The effect was reversed more than 10 h but less than 24 h after putrescine treatment, even though polyamines were repleted 4 h after putrescine and spermidine were added. DFMO did not substantially affect intracellular calcium release or the timing of the opening and closing of plasma membrane calcium channels. These findings support the notion that calcium signaling may be a target for inhibitors of polyamine metabolism.
Cancer Res 1992 Dec 15
PMID:alpha-Difluoromethylornithine alters calcium signaling in platelet-derived growth factor-stimulated A172 brain tumor cells in culture. 145 66

B cells derived from peripheral-blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from a patient with a high serum antibody titer to autologous melanoma were transformed with Epstein-Barr virus (EBV) and evaluated for reactivity against autologous tumor. B cells producing antibody reactive with autologous tumor and unreactive with normal fibroblasts were detected both in TIL and in PBL. One cell line derived from PBL and another derived from TIL sustained production of tumor-reactive antibody for 10 weeks and over 15 months respectively. The cell line derived from PBL, 2D11, produced an antibody reactive with a trypsin-resistant antigen expressed on the cell membrane of autologous and allogeneic melanoma cell lines. The cell line derived from TIL, 1F6, produced an antibody reactive with a cell-surface glycoprotein expressed by 5 autologous melanoma cell lines derived from 5 different metastases and 16/19 allogeneic melanoma cell lines. 1F6 also showed reactivity with cell lines derived from a blue nevus, a congenital nevus, an astrocytoma, and 1/4 renal-cell carcinomas; but it was not reactive with 5 foreskin melanocyte cell lines, 2 normal fibroblast lines, 5 leukemia/lymphoma lines, 8 lung-cancer lines, 8 glioblastoma lines, or lines derived from 1 ovarian carcinoma, 1 colon carcinoma, 1 vulvar carcinoma, 1 fibrosarcoma, 1 murine melanoma, or 4 murine leukemia/lymphomas. We describe here an antibody that detects a new melanoma specificity obtained by EBV transformation of tumor-infiltrating B cells.
Int J Cancer 1992 Dec 02
PMID:Analysis of two human monoclonal antibodies against melanoma. 145 38

A panel of 60 human tumor cell lines is currently being used in the U.S. National Cancer Institute's in vitro anticancer drug screen. The panel is organized into 7 subpanels; 6 leukemia/lymphoma lines comprise one subpanel, and 54 other lines are organized into subpanels representing solid tumors of the central nervous system (CNS), colon, lung, ovaries, kidneys and melanomas. In the present study, the leukemia and lymphoma cell lines were analyzed by flow cytometry for appropriate CD antigens; all but 1 line showed patterns of expression consistent with their reported derivations. The solid tumor lines were characterized individually using morphological and immunocytochemical techniques to determine their relative degrees of representativity for the subpanels within which they are currently grouped. Histological, histochemical and ultrastructural examinations were performed on cell lines grown under identical conventional culture conditions and as xenografts in nude mice. Immunocytochemistry using panels of antibodies raised against 6 types of intermediate filaments, 7 adenocarcinoma-associated antigens, 7 melanoma/neuro-ectodermal-associated antigens, 3 neuroendocrine-associated antigens, 9 urinary tract associated antigens, and 4 markers of muscle differentiation was done on cells grown in monolayer culture. Central nervous system (CNS) cell lines lacked expression of glial fibrillary acidic protein, but all had other features consistent with derivation from glioblastoma. Lines derived from adenocarcinomas of the colon, lung and ovary, for the most part, expressed adenocarcinoma-associated antigens and showed histological and/or ultrastructural evidence of gland formation and other adenomatous features. Most of these lines were poorly differentiated. Lines derived from large-cell and squamous-cell cancers also showed some characteristics consistent with their reported origins, except for one line which showed immunocytochemical and morphologic characteristics consistent with rhabdomyosarcoma. The 2 lines derived from small cell lung cancer (SCLC) lacked neurosecretory granules and 3 other SCLC markers but showed morphologic features consistent with SCLC. Most melanoma cell lines strongly expressed melanoma-associated antigens and were morphologically similar to human melanoma. Five lines produced premelanosomes, melanosomes or melanin. Most of the renal cancer cell lines showed morphologic or immunocytochemical features consistent with renal clear cell carcinoma. Collectively, these morphological and immunocytochemical analyses provide information concerning tissue of origin, tumor type, degree of differentiation and other biologic features essential to the use of these lines in a disease-oriented in vitro antitumor drug screen and to the interpretation of data derived therefrom.
 ...
PMID:Morphological and immunocytochemical characteristics of human tumor cell lines for use in a disease-oriented anticancer drug screen. 150 99

Integrins are heterodimeric transmembrane proteins with large ectodomains and a short cytoplasmic tail inside the cell. They mediate cell adhesion to extracellular matrix proteins and to the surfaces of other cells. In many cases the sequence recognised by the integrins in the extracellular matrix proteins is the tripeptide Arg-Gly-Asp (RGD). Short synthetic peptides containing this sequence can inhibit invasion in vitro and tumour dissemination in vivo. Thus, the alpha 5 beta 1 fibronectin binding integrin appears to be the key integrin in the invasion of at least melanoma, osteosarcoma and glioblastoma cells. Modulation of the level and activities of this integrin can suppress invasion, whereas the alpha v beta 3 vitronectin binding integrin appears to be associated with increased invasiveness. There is increasing evidence that some of these effects are mediated through signals elicited by the binding of integrins to their target proteins. This possibility has generated a great deal of interest in the cytoplasmic molecules that might mediate the integrin-associated signalling.
Br J Cancer 1992 Aug
PMID:The Walter Herbert Lecture. Control of cell motility and tumour invasion by extracellular matrix interactions. 150 96

Anthracyclines are important antitumor agents used in the treatment of solid tumors, lymphomas, and acute lymphoblastic as well as myelocytic leukemias. The clinical utility of agents such as doxorubicin and daunorubicin and their well-characterized cardiotoxicity have prompted many efforts to develop analogs that retain the desired spectrum of activity but are less cardiotoxic. One such analog is idarubicin (4-demethoxydaunorubicin), which is currently under study in the treatment of adult and pediatric leukemias. The major circulating metabolite of idarubicin is the alcohol product of ketoreductase biotransformation, idarubicinol. Following the administration of idarubicin to adult or pediatric patients, systemic exposure to idarubicinol is greater than that to idarubicin. Moreover, we have also documented the presence of idarubicinol in the cerebrospinal fluid of pediatric patients who have received idarubicin. Idarubicinol has been reported to have greater cytotoxic activity than other anthracycline alcohol metabolites, which are regarded as much less active products of metabolism. We therefore evaluated the growth-inhibitory and DNA-damaging activities of idarubicin, daunorubicin, doxorubicin, epirubicin, and their alcohol metabolites against three relevant (CCRF-CEM lymphoblastic leukemia, K562 myelogenous leukemia, and U87-MG glioblastoma) human tumor cell lines. We found that whereas idarubicin was 2-5 times more potent than the other three anthracycline analogs against these tumor cell lines, idarubicinol was 16-122 times more active than the other alcohol metabolites against the same three cell lines. In addition, idarubicinol and the parent drug idarubicin were equipotent, unlike the other anthracycline alcohol metabolites, which were much less cytotoxic than the corresponding parent drugs. We also assessed the ability of the four parent drugs and their alcohol metabolites to induce DNA single-strand breaks. Idarubicin was more potent than the other three anthracycline analogs and idarubicinol was much more effective than the other alcohol metabolites in inducing DNA damage. These studies in human leukemia and human glioblastoma cell lines support the hypothesis that idarubicinol plays an important role in the antitumor activity of idarubicin and that the activities of idarubicin and idarubicinol are related to their ability to damage DNA.
Cancer Chemother Pharmacol 1992
PMID:Anthracyclines and their C-13 alcohol metabolites: growth inhibition and DNA damage following incubation with human tumor cells in culture. 158 80

The presence of interleukin-8 (IL-8), a leukocyte chemotactic factor, was examined in primary and metastatic central nervous system tumors and in nonneoplastic acute meningoencephalitides. In vitro: (a) 11 of 12 glioblastoma cell lines constitutively expressed IL-8 mRNA; (b) 5 of 6 of these cell lines secreted IL-8 protein as detected by enzyme-linked immunosorbent assay and a glucosaminidase release bioassay; and (c) IL-1 beta or tumor necrosis factor was able to augment both IL-8 mRNA steady state levels and protein secretion of all cell lines tested except IN-319. IL-8 was also found in vivo. (a) IL-8 poly A+ mRNA was detected in 2 of 2 low grade astrocytomas, 1 of 2 anaplastic astrocytomas, and 6 of 6 glioblastomas. (b) IL-8 protein was present in the cyst fluid of 1 of 4 low grade astrocytomas, 1 anaplastic astrocytoma, 2 of 2 glioblastomas, 1 oligodendroglioma grade III, and one central nervous system cervical carcinoma metastasis. (c) The cerebrospinal fluid of 3 of 4 metastatic lymphomas, 2 of 16 glioblastomas, 1 of 2 low grade astrocytomas, but none of 3 anaplastic astrocytomas and none of 9 meningiomas contained IL-8. The presence of IL-8 was not restricted to central nervous system tumors as 2 of 2 bacterial meningitis and 5 of 5 acute viral meningitis patients contained considerable IL-8 levels in the cerebrospinal fluid. (d) Immunohistochemical analysis showed IL-8 immunoreactivity in perivascular tumor cells in 11 of 15 glioblastoma sections. These data suggest that IL-8 secretion could be a key factor involved in the determination of the lymphoid infiltrates observed in brain tumors and the development of cerebrospinal fluid pleocytosis in meningoencephalitides.
Cancer Res 1992 Aug 15
PMID:Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system. 164 27

The proportion of ganglioside GD3 increases in glioma tissue and GD3 content is correlated with malignancy of gliomas. This ganglioside can be detected in the sera of patients with glioma by thin-layer chromatographic analysis. Ganglioside GD3 was not detected in the sera of healthy donors and astrocytoma grade 2 patients. However, serum GD3 was detected in one of three astrocytoma grade 3 patients and seven of nine glioblastoma patients. These results show that shedding of GD3 increases in proportion to the degree of malignancy of gliomas. Nevertheless, all of the glioblastoma patients in this study were advanced cases. Considering the high reliability of radiological diagnostic techniques in the neurosurgical field, further study will be necessary to clarify the relationships between the GD3 level in serum and the properties of tumours.
 ...
PMID:Ganglioside GD3 shedding by human gliomas. 164 61

The methods of quantitative immunoelectrophoresis and indirect immunofluorescence were used study the content of glial fibrillary acid protein in 10 serially reinoculated rat gliomas induced primarily by ethylnitrosourea (a total of 135 tumors). It was found that the GFAP content reduced with increase of malignancy. However, wide scattering of the GFAP content in some of the tumors was characteristic of all strains. In the group of slowly growing glial tumors (2 malignant astrocytomas and one malignant oligoastrocytoma) the GFAP content ranged from 50 to 600% and exceeded the normal content two-to threefold on the average. In the group of highly malignant gliomas (4 malignant ependymomas, 2 malignant gliomas, and one glioblastoma) the GFAP content was within the limits of 65-120%. In most cases the GFAP level was below normal or could not be determined at all. At the same time, tumors with a high GFAP content were encountered. The GFAP-positive cells were unevenly distributed in the gliomas: separately, in foci, and around the vessels. Their number increased in the direction of the periphery of the tumor. Intensive fluorescence was noted on the tumor--brain borderline. The content of protein S-100 in the experimental gliomas was always below normal.
 ...
PMID:[The distribution of glial fibrillary acidic protein and protein S-100 in experimental brain tumors in rats]. 164 19

We report here that a neutralizing mouse monoclonal antibody against basic FGF inhibited both anchorage-dependent and anchorage-independent growth of U-87MG and T98G human glioblastoma cells and HeLa cells, all of which express both the basic FGF and the FGF receptor genes. In addition, the subcutaneous administration of this antibody significantly suppressed the tumor development of these tumor cells in nude mice. Therefore, basic FGF plays an important role in neoplastic growth of these cells. The neutralization of basic FGF will be effective in controlling the growth of tumors, such as glioblastoma and other cancer cells which bear basic FGF and FGF receptors.
 ...
PMID:Inhibition of cell growth and tumorigenesis of human glioblastoma cells by a neutralizing antibody against human basic fibroblast growth factor. 165 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>