Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vitro chemosensitivity study of both biopsy specimens and surgically resected tumors of advanced gastric cancer from 12 patients was evaluated using the succinate dehydrogenase inhibition (SDI) test. A decrease in succinate dehydrogenase (SD) activity as an indicator of chemosensitivity was determined using cisplatin (CDDP), etoposide (VP-16), and mitomycin C (MMC). In this study, 29 of a total 36 experiments were evaluable (80.6%) and significant correlations were found in all three of the antitumor drugs (P < 0.03). This finding suggests that the SDI test using biopsy specimens may prove valuable for assessing the preoperative chemosensitivity of advanced gastric cancer.
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PMID:The succinate dehydrogenase inhibition test for evaluating biopsy specimens and resected tumors of advanced gastric cancer. 147 90

The purpose of this study is to assess effects of fibroblasts in the vitro chemosensitivity testing on human lung cancer cells and to remove them. Fourteen lung cancer cell lines and 14 fibroblasts derived from resected specimens of lung cancers were used, whose S.D (succinate dehydrogenase) activities were measured with MTT colorimetric assay. The chemosensitivity of a lung cancer cell alone was compared with that of mixed cancer cell and fibroblast. As results, S.D activities of fibroblasts were less 2-4 fold than those of lung cancer cells. Fibroblasts were as sensitive to CDDP, MMC and 5-FU as lung cancer cells, but more sensitive to ADM and VP-16 than them. When sensitivity testings were performed on mixed cancer cells and fibroblasts, or mixed cancer cells and conditioned media of fibroblasts to CDDP with 3 day's incubation times, the sensitivity was affected in 61%, or 10% of all the pairs, respectively. However, when these tests were done without any incubation times, the sensitivity was not affected. Therefore, it was suggested that anticancer drugs had to be simultaneously added when single cell suspensions were plated if resected specimens were used in a anticancer drug sensitivity test.
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PMID:[A study of fibroblasts in the chemosensitivity testing on human lung cancer cell lines]. 180 80

The mechanism of action of 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside) (VP-16), an important antitumor agent, is unclear. There is evidence that DNA may be the target of action because VP-16 causes single-strand and double-strand breaks in DNA and produces cytotoxicity over a similar dose range. We have hypothesized that an enzyme system, such as dehydrogenase, catalyzes an oxidation-reduction reaction involving the pendant phenolic group which forms an active metabolite that causes the DNA damage and cytotoxicity. To test our hypothesis, we investigated the effect of disulfiram, an aldehyde dehydrogenase inhibitor, and its metabolite, diethyldithiocarbamate, on VP-16-induced DNA damage in L1210 cells. Using the alkaline elution technique to assay DNA damage, we found that disulfiram and diethyldithiocerbamate inhibited VP-16-induced single-strand breaks. Both compounds were also capable of significantly reducing VP-16-induced cytotoxicity. Oxalic acid, pyrophosphate, and malonic acid, competitive inhibitors of succinate dehydrogenase, and the naturally occurring dehydrogenase substrates, succinic acid, beta-glycerophosphate, and isocitric acid, also blocked the effects of VP-16. Free-radical scavengers were also studied. While sodium benzoate was particularly effective in preventing drug-induced DNA damage and cytotoxicity, a number of other scavengers were not. Our data are consistent with the hypothesis that VP-16 is activated by an enzyme such as a dehydrogenase which transforms it into an active intermediate resulting in DNA damage and, consequently, cell death.
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PMID:Inhibition of etoposide-induced DNA damage and cytotoxicity in L1210 cells by dehydrogenase inhibitors and other agents. 631 74