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)

One must know tumor cell kinetics in order to devise a rational drug regimen for gliomas. With tritiated thymidine, the Labelling Index of astrocytomas is less than 1 per 100; of glioblastomas from 5-10 per 100. The duration of S phase is fairly constant, ranging from 7 to 10 hours. Double radioautography reveals a cell cycle time of 2 to 3 days and a Growth Fraction of 10 to 30 per 100 in glioblastomas. Calculations based on volume of tumor at recurrence after a gross total resection, analysis of primer dependent D.N.A. polymerase (P.D.P.), and analysis of cells by Flow Microfluorometer, all confirm these approximate figures. Thus most of the cells of a glioma are not sensitive to a cell-cycle phase specific drug. Such an agent, if given, should be administered over a 2 to 3 day period, in order to affect as many cells as possible. The most important part of a drug regimen should be an agent which attacks non-proliferating as well as proliferating cells, such as an alkylating agent. The effects of various drugs and schedules can be examined by animal models with the technqiue of colony forming efficiency.
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PMID:Current status of population kinetics in gliomas. 19 96

In an effort to optimize immunocytochemical methods to evaluate cell kinetics in brain tumors, we studied two newly-developed antibodies which react with formalin resistant epitopes of Proliferating Cellular Nuclear Antigen (PCNA) and Ki-67. These results were compared with standard flow cytometric cell cycle data from the same tumor specimens to determine if these methods correlate with each other, and whether retrospective analysis using these antibodies is feasible for cell kinetic analysis of brain tumors. Thirty-one specimens of glial tumors submitted for flow cytometry during 1992 were also reacted with antibodies to PCNA (PC-10) and Ki-67 (MIB-1). Flow cytometry scores for S-phase Fraction were compared with immunocytochemical scores for both antibodies, using an arbitrary rating of 1 (low, < 4%), 2 (intermediate, 4-6%), 3 (high, > 6%), and 1 (< 25% positive), 2 (26-75% positive), 3 (> 75% positive), respectively. MIB-1 results were found to correlate significantly with the S-phase fraction as determined by flow cytometry. The MIB-1 data showed a trend toward underestimating, i.e., lower scores, the proliferative index compared with flow cytometry. There was less of a correlation between PC-10 antibody scores and flow cytometry S-phase fraction, as PC-10 immunostaining typically overestimated the proliferative rate of brain tumors when compared with flow cytometry. There was an exact correlation between PC-10 and MIB-1 in only 4 cases, whereas in the remaining specimens, PC-10 results were always higher than MIB-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of proliferative grade in glial neoplasms using antibodies to the Ki-67 defined antigen and PCNA in formalin fixed, deparaffinized tissues. 756 3

We have examined the formation of DNA in rat glioma cells. Cytotoxicity was induced in the cells using BCNU (1,3-bis(2-chloroethyl)-1-nitroso-urea) in the presence or absence of CPZ (chlorpromazine). There was impaired formation of DNA in cells treated with BCNU. This was further enhanced in cells treated with both BCNU and CPZ. In the latter case we did not find any intact high molecular weight DNA.
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PMID:Reduced formation of high molecular weight DNA in murine gliomas treated with nitrosourea and chlorpromazine. 807 63

2-Chloro-10-[3(-dimethylamino)propyl]phenothiazine mono hydrochloride (chlorpromazine; CPZ) is an antipsychotic agent that was originally developed to control psychotic disorders. The cytotoxic properties of the CPZ are well known, but its mechanism of action is poorly understood. In this study, we investigated the role of apoptosis and autophagy in CPZ-induced cytotoxicity in U-87MG glioma cells. CPZ treatment inhibited cell proliferation and long-term clonogenic survival. Additionally, CPZ triggered autophagy, as indicated by electron microscopy and accumulation of the membrane form of microtubule-associated protein 1 light chain 3 (LC3-II); however, CPZ did not induce apoptosis. Inhibition of autophagy by expression of Beclin 1 small interfering RNA (siRNA) in U-87MG cells attenuated CPZ-induced LC3-II formation. Furthermore, U-87MG cells expressing Beclin 1 siRNA attenuated CPZ-induced cell death. CPZ inhibited phosphatidylinositol 3-kinase (PI3K)/AKT/ mTOR pathway in U-87MG cells. Treatment with LY294002, a PI3K inhibitor, alone increased the accumulation of LC3-II and potentiated the effect of CPZ. In contrast, exogenous expression of AKT partially inhibited CPZ-induced LC3-II formation. When U-87MG cells were implanted into the brain of athymic nude mouse, CPZ triggered autophagy and inhibited xenograft tumor growth. These results provided the first evidence that CPZ-induced cytotoxicity is mediated through autophagic cell death in PTEN (phosphatase and tensin homolog deleted on chromosome 10)-null U-87MG glioma cells by inhibiting PI3K/AKT/mTOR pathway.
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PMID:The antipsychotic agent chlorpromazine induces autophagic cell death by inhibiting the Akt/mTOR pathway in human U-87MG glioma cells. 2368 52