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)

1. After s.c. and intracerebral (i.c.) inoculation, 4 neurogenic tumors of the rat (3 malignant neurinomas, 1 polymorphcellular glioma) revealed an altogether weak response towards a monotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 1-(2-chloroethyl)-3-(4-Methylcyclohexyl)-1-nitro sourea (MeCCNU), 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (OH-ethyl-CCNU), 2-[3-(2-chloroethyl)-3-nitrosoureidol]-D-glucopyranose (chlorozotocin), 5-(3,3-dimethyl-1-triazeno)-imidazol-4-carboxamide (DTIC). Cyclophosphamide (CPA) which was investigated for comparison showed the greatest therapeutic activity; in an equitoxic dosage (less than or equal to LD10), in all 4 s.c. tumors, partial or complete regression were effected only by CPA. 2. If the passage number increases, the response of transplanted neurogenic rat tumors to monochemotherapy can both increase and decrease. 3. In the monotherapy of 3 malignant neurinomas we were unable, on the whole, to observe a higher sensitivity after s.c. inoculation as compared with an i.c. inoculation of the tumor, despite a varying effectiveness of the single substances. 4. In the monotherapy of the polymorphcellular glioma a better response of the i.c. inoculated tumor was recognizable compared to the s.c. inoculated tumor. 5. A combination chemotherapy of a malignant neurinoma after s.c. and i.c. inoculation with vincristine, CPA, OH-ethyl-CNU and MeCcNU yielded a significant increase in life-span of animals with i.c. tumor, whereas s.c. tumors showed no significant growth inhibition. y. Transplanted neurogenic tumors of the rat could serve at less sensitive models for the investigation of new nitrosoureas.
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PMID:[Chemotherapy of transplanted neurogenic tumors in the rat (author's transl)]. 626 27

The purpose of this study has been to measure the formation and repair of individual DNA alkylation products in 9L, 9L-2 and BTRC-19 cell lines after treatment with 1-(2-chloroethyl)-1-nitrosourea (CNU). The levels of seven DNA adducts N7-(2-hydroxyethyl)-guanine, N7-(2-chloroethyl)-guanine; 1,2-(diguan-7-yl)-ethane, N1-(2-hydroxyethyl)-2-deoxyguanosine, 1-(N1-2-deoxyguanosinyl), 2-(N3-2-deoxycytidyl)-ethane, O(6)-(2-hydroxyethyl)-2-deoxyguanosine and phosphotriesters were separated by HPLC and quantified by liquid scintillation counting. The levels of N7-(2-hydroxyethyl)-guanine, N7-(2-chloroethyl)-guanine; O(6)-(2-hydroxyethyl)-2-deoxyguanosine and phosphotriesters were not significantly different in the three glioma lines. Furthermore, comparison of the levels of these products in treated cells with the levels formed in purified DNA suggest that they were not actively repaired over the 6h interval. The levels of 1,2-(diguan-7-yl)-ethane and N1-(2-hydroxyethyl)-2-deoxyguanosine were reduced in 9L-2 and significantly reduced in BTRC-19 (P = 0.003) compared to 9L. Analysis of the data suggests that the reduction in the level of N1-(2-hydroxyethyl)-2-deoxyguanosine was due to repair of its precursor O(6)-ClEtdG by O(6)-alkylguanine-DNA-alkyltransferase (AGT). The level of the crosslinked product 1-(N1-2-deoxyguanosinyl), 2-(N3-2-deoxycytidyl)-ethane was significantly reduced (P < 0.001) in both 9L-2 and BTRC-19 as compared to 9L. Reduction in the level of 1-(N1-2-deoxyguanosinyl), 2-(N3-2-deoxycytidyl)-ethane in 9L-2 and BTRC-19 are consistent with repair of the precursor alkylation product O(6)-ClEtdG by AGT. This study demonstrates that there are very significant differences in the rates of removal of individual DNA adducts formed by CNU treatment of the glioma cell lines.
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PMID:Repair of DNA alkylation products formed in 9L cell lines treated with 1-(2-chloroethyl)-1-nitrosourea. 1251 14

Glioblastoma multiforme is the most severe form of brain cancer. First line therapy includes the methylating agent temozolomide and/or the chloroethylating nitrosoureas [1-(2-chloroethyl)-1-nitrosourea; CNU] nimustine [1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea; ACNU], carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], or lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU]. The mechanism of cell death after CNU treatment is largely unknown. Here we show that ACNU and BCNU induce apoptosis in U87MG [p53 wild-type (p53wt)] and U138MG [p53 mutant (p53mt)] glioma cells. However, contrary to what we observed previously for temozolomide, chloroethylating drugs are more toxic for p53-mutated glioma cells and induce both apoptosis and necrosis. Inactivation of p53 by pifithrin-alpha or siRNA down-regulation sensitized p53wt but not p53mt glioma cells to ACNU and BCNU. ACNU and BCNU provoke the formation of DNA double-strand breaks (DSB) in glioma cells that precede the onset of apoptosis and necrosis. Although these DSBs are repaired in p53wt cells, they accumulate in p53mt cells. Therefore, functional p53 seems to stimulate the repair of CNU-induced cross-links and/or DSBs generated from CNU-induced lesions. Expression analysis revealed an up-regulation of xpc and ddb2 mRNA in response to ACNU in U87MG but not U138MG cells, indicating p53 regulates a pathway that involves these DNA repair proteins. ACNU-induced apoptosis in p53wt glioma cells is executed via both the extrinsic and intrinsic apoptotic pathway, whereas in p53mt glioma cells, the mitochondrial pathway becomes activated. The data suggest that p53 has opposing effects in gliomas treated with methylating or chloroethylating agents and, therefore, the p53 status should be taken into account when deciding which therapeutic drug to use.
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PMID:Differential sensitivity of malignant glioma cells to methylating and chloroethylating anticancer drugs: p53 determines the switch by regulating xpc, ddb2, and DNA double-strand breaks. 1808 19

This study has investigated if individual DNA adducts formed in human glioma cells treated with (3)H-1-(2-chloroethyl)-1-nitrosourea ((3)H-CNU) could be used as molecular dosimeters of response after CENU treatment. The levels of individual DNA alkylation products were compared with the induction of cytotoxicity in six human glioma cell lines after treatment with (3)H-CNU. The levels of seven DNA adducts N7-(2-hydroxyethyl)guanine, (N7-HOEtG); N7-(2-chloroethyl)guanine, (N7-ClEtG); 1,2-[diguan-7-yl]-ethane, (N7-bis-G); N1-(2-hydroxyethyl)-2-deoxyguanosine, N1-HOEtdG; 1-[N1-2-deoxyguanosinyl], 2-[N3-2-deoxycytidyl]-ethane, dG-dC; O(6)-(2-hydroxyethyl)-2-deoxyguanosine, O(6)-HOEtdG and phosphotriesters (PTE), were quantified in each of the cell lines following treatment with (3)H-CNU. The levels of N7-HOEtG, N7-ClEtG; O(6)-HOEtdG and PTE were not significantly different in the glioma lines and their levels were not associated with the induction of cytotoxicity by CNU treatment. The levels of N7-bis-G, N1-HOEtdG and dG-dC crosslink were significantly lower in both SF-188 and SF-763 cell lines compared to their levels in U87MG, U251MG and SF-126. There was a significant correlation between CNU LD(10) values and with the levels of levels of N7-bis-G and N1-HOEtdG (R = -0.91, P = 0.01) and dG-dC crosslink (R = -0.94, P = 0.005) in the glioma cell lines. Pretreatment of SF-188 cells with varying concentrations of MNU prior to CNU treatment resulted in no change in the levels of N7-HOEtG, N7-ClEtG; O(6)-HOEtdG and PTE and a dose dependent increase in the levels of N7-bis-G, N1-HOEtdG and dG-dC crosslink. Taken together, these results suggest that the levels of the N7-bis-G, N1-HOEtdG and dG-dC crosslink could be used as molecular dosimeters of therapeutic response following treatment with BCNU or related CENU.
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PMID:DNA alkylation products formed by 1-(2-chloroethyl)-1-nitrosourea as molecular dosimeters of therapeutic response. 1897 9