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 soft agar technique for culturing human clonogenic tumor cells has been usefully applied for predicting individual clinical responses to chemotherapy, for screening of new antineoplastic drugs, and in basic biological research. The counting of colonies formed by clonogenic cells is, however, a rather time consuming and inaccurate procedure. We here report a method to combine the easy and precise registration of DNA-synthesis by 3H-thymidine incorporation with the ability of soft agar to permit proliferation of clonogenic cells and inhibit proliferation of non-neoplastic cells. The glioma cell lines U 251 MG and T-MG 1, the benignant glia cells T-BG 1, T-BG 2, T-BG 3 and fibroblasts were cultured in Furcellaran gel. Twenty hours before harvesting 3H-thymidine was added. The Furcellaran gel was resolved by 50 mM LiI. The cells were trapped on glass fiber filters and incorporated radioactivity was measured. 3H-thymidine incorporation in malignant cells increased exponentially with time, while 3H-thymidine incorporation in the benignant glia cells and fibroblasts was inhibited. The correlation between number of colonies counted after 16 days and 3H-thymidine incorporation registered after different culture times was very good. The correlation was best when the cultures were harvested after 8 days (r = 0.95), indicating that it is possible to reduce the assay time. The five glioma biopsies tested grew well with a mean plating efficiency of 0.4% (range 0.02-1.8%). The most intense proliferation seemed to take place during the first week in culture. The good correlation between 3H-thymidine incorporation on day 7 and colony number on day 14 (r = 0.93), indicate that reduction of assay time is possible also for the glioma biopsies.
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PMID:A new technique to register proliferation of clonogenic cells from brain tumors. 405 50

The in vitro cytotoxicity of 8-carbamoyl-3-methylimidazo [5,1-d]-1,2,3,5-tetrazine-4(3H)-one (temozolomide) with concurrent X-irradiation was examined in a human glioblastoma cell line (U373MG) as a potential radio-chemotherapeutic treatment for malignant glioma. The combination was also examined in a human colorectal adenocarcinoma (Mawi) which had 100-fold greater O6-alkylguanine-DNA alkyltransferase (AGT) activity, a DNA-repair protein which confers resistance to temozolomide. A comparison of IC50 values indicated U373MG to be over 32-fold more sensitive to temozolomide than Mawi, but slightly more resistant to X-irradiation (p < 0.035; unpaired two-tailed t-test). Temozolomide and X-irradiation proved largely additive in U373MG by isobologram analysis (50% iso-effect) and the addition of 10 microM temozolomide to 1-2 Gy of X-irradiation increased cell kill by 2.5- to 3.0-fold. However, the combination was antagonistic in Mawi: an effect attributed to AGT induction by X-irradiation as the antagonism was removed by co-incubation with the AGT inhibitor O6-benzylguanine (O6-BG 1 microM; 24 h). O6-BG did not affect the radiation dose-response curve, but significantly increased temozolomide cytotoxicity (p < 0.015). In conclusion, the combination of temozolomide with radiation is at best additive, but could nonetheless by of considerable therapeutic benefit in glioma, particularly if administered for prolonged periods. If AGT induction compromises the efficacy of this therapy, it may be circumvented with an appropriate inhibitor such as O6-BG.
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PMID:In vitro evaluation of temozolomide combined with X-irradiation. 914 18