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)

The chemosensitivities of 41 poorly differentiated gastric cancer tissues were compared with that of 16 well differentiated tissues, using the in vitro succinate dehydrogenase inhibition test. These human tissues obtained at the time of surgery were exposed to six different antitumor drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was determined as positive when the succinate dehydrogenase (SD) activity of the drug exposed cells was decreased to below 50% of that of control cells, on day 3 of exposure. Decrease in SD activity was remarkable in the poorly differentiated tissues, compared to the well differentiated tissues, exposed to ADM, MMC, DDP and 5-FU. The sensitive rates were higher in the poorly differentiated tissues than in the well differentiated tissues, against all six antitumor drugs. Sixty-three per cent of the poorly differentiated tissues were sensitive to more than three antitumor drugs, in an identical tissue, but the rate was only 19% in the well differentiated tissues. The resistant rates to all drugs tested were 20% in the poorly differentiated and 31% in the well differentiated tissues. This would indicate that patients with a poorly differentiated gastric cancer will probably show a better response to antitumor drugs, compared to those with a well differentiated type.
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PMID:Poorly differentiated human gastric carcinoma is more sensitive to antitumor drugs than is well differentiated carcinoma. 303 3

The sensitivity to 1-hexylcarbamoyl-5-fluorouracil (HCFU) of 25 colorectal cancer tissues was compared with that of six antitumor drugs: carboquone (CQ), Adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP), and 5-fluorouracil (5-FU), using the in vitro succinate dehydrogenase inhibition (SDI) test. Chemosensitivity was determined to be positive when the succinate dehydrogenase (SD) activity of the drug-exposed cells, at ten times the peak plasma concentration, was decreased to below 50 percent of that of control cells on day 3 of exposure. Decrease in SD activity was remarkable in cases of exposure to HCFU, compared with six other drugs. The sensitivity rates were 32 percent for CQ, 40 percent for ADM, 24 percent for MMC, 28 percent for ACR, 32 percent for DDP, 16 percent for 5-FU, and 68 percent for HCFU. The sensitivity rate for at least one of the six drugs (CQ, ADM, MMC, ACR, DDP, and 5-FU) was 52 percent, but was 80 percent when HCFU was taken into account. Since colorectal cancer tissues are resistant to various antitumor drugs, the chemosensitivity test of HCFU should aid in determining the effects of a particular drug for an individual patient.
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PMID:Colorectal carcinoma in vitro is more sensitive to 1-hexylcarbamoyl-5-fluorouracil compared with six other antitumor drugs: carboquone, Adriamycin, mitomycin C, aclacinomycin A, cisplatin, 5-fluorouracil. 313 Feb 39

An in vitro chemosensitivity test, the succinate dehydrogenase inhibition (SDI) test, was used to examine 16 pairs of samples obtained simultaneously from primary and metastatic lesions of clinical gastric cancer. Concerning the metastases, 11 were in the lymph nodes and five in the liver. The chemosensitivities of metastatic lesions against six anti-tumour drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), and 5-fluorouracil (5-FU), differed from those in the primary lesions, and there were no correlations of chemosensitivities between the primary and the metastatic lesions against these drugs, except for DDP. The lymph nodes were more sensitive to CQ, ADM, MMC, DDP, ACR and 5-FU, while the liver was less sensitive than the primary lesions to CQ, ADM, MMC, DDP, and ACR. Our findings indicate that in patients with lymph node metastasis, there is a sensitivity to anti-tumour drugs, while in cases of liver metastasis, drug treatment may be less effective. We propose that chemosensitivity testing should be done when attempting to design anti-tumour drugs.
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PMID:Chemosensitivity differences between primary and metastatic lesions of clinical gastric cancer. 319 5

The chemosensitivity result of the succinate dehydrogenase inhibition (SDI) test was compared with that of the subrenal capsule (SRC) assay in 23 human tumor tissues exposed to adriamycin (ADM), mitomycin C (MMC), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was considered as positive when the succinate dehydrogenase (SD) activity of the drug-exposed cells was decreased to below 50% of that of control cells on day 3 in the SDI test, and the tumor size on day 6 was decreased to below -10% of that on day 0 in the SRC assay. Correlation rates between the decrease of SD activity in the SDI test and the decrease of tumor size in the SRC assay, using 23 evaluable cases in both assays, were r = 0.717 for ADM, r = 0.699 for MMC, r = 0.796 for DDP and r = 0.735 for 5-FU. The correlations of the chemosensitivity results were 73.9% for ADM, 73.9% for MMC, 82.6% for DDP and 60.9% for 5-FU. A positive correlation was noted between the in vitro and in vivo chemosensitivity results. This SDI test can serve as an effective tool for chemosensitivity testing.
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PMID:Comparison between succinate dehydrogenase inhibition test and subrenal capsule assay for chemosensitivity testing. 357 51

We retrospectively evaluated the clinical usefulness of the succinate dehydrogenase inhibition (SDI) test as a chemosensitivity test, using 168 resected specimens of gastric cancer, with special reference to the correlation between the results of the SDI test and clinical effects of the corresponding chemotherapy. The rate of sensitivity of these tissues to DDP, CQ, ACR, MMC, ADM, and 5-FU were 63.5%, 54.2%, 47.4%, 42.9%, 31.4%, and 10.8%, respectively. Survival rates for patients with a positive chemosensitivity to MMC and postoperatively prescribed more than 20 mg of MMC were significantly better than those without sensitivity to MMC, even when treated with MMC, although no statistical differences existed in clinicopathologic factors between the two groups. We conclude that the SDI test for human gastric cancer is a rapid, reliable, and useful assay to determine the compatibility between the results of assay and the clinical effects of corresponding chemotherapy. We propose that the regimen of postoperative adjuvant chemotherapy be tailored according to results of the SDI test, using tissues resected from individual patients.
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PMID:Clinical value of SDI test for predicting effect of postoperative chemotherapy for patients with gastric cancer. 805 84

The inhibition of [14C]thymidine incorporation into DNA of tumor and normal tissues of L1210-leukemia-bearing mice by single doses of cis-diamminedichloroplatinum (II) (cisplatin, cis-DDP) and two newly synthesized platinum (II) complexes containing as ligands dimethyl aminomethylphosphine oxide (complex I) and methyl bis(aminomethyl)phosphine oxide (complex II) was studied and used as an indication of drug toxicity. All three complexes caused selective inhibition of precursor incorporation in L1210 cells as compared to host tissue cells. cis-DDP caused a complete block of incorporated thymidine in tumor cells during more than 48 h, whereas in intestinal mucosa and bone marrow reverse inhibition was observed. In spleen, liver and kidney the inhibition was about 50% and endured up to 96 h without reversal. Complex I treatment of L1210 cells resulted in an earlier recovery of thymidine incorporation into DNA in comparison with cis-DDP. Towards all other normal tissues compound I was less toxic than cis-DDP. Unlike cis-DDP and complex I, complex II was less active against L1210 cells and most toxic against bone marrow and kidney.
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PMID:Inhibition of DNA synthesis in different tissues of L1210-leukemia-bearing mice by new platinum (II) complexes. 844 64

The results of two types of in vitro chemosensitivity tests, namely, the human tumor clonogenic assay (HTCA) and the succinic dehydrogenase inhibition assay (SDIA), for solid tumors, including stomach, colorectal and lung cancers, were analyzed and their correlation with clinical effects evaluated. The anticancer agents employed were mitomycin C (MMC), 5-fluorouracil (5-FU), adriamycin (ADM) and cisplatin (DDP). The evaluability rates of the assays were 54.5% for HTCA and 89.0% for SDIA. Among the 29 cases with evaluable lesions subjected to HTCA, there were 4 true positives, 9 false positives, and 16 true negatives, whereas among the 32 cases subjected to SDIA, the corresponding numbers were 2, 6, and 24, respectively. There were no false negatives for either assay, the accuracy of prediction for HTCA being 69.0% and for SDIA, 81.3%. The true positives of both assays included one complete response (CR) and five partial responses (PR), although the eventual outcome was cancer death in all cases. Interestingly, in five out of the six true positive cases, the agent involved was either ADM or DDP, both the which are usually regarded as "second line" anticancer agents for gastrointestinal carcinomas.
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PMID:The predictability of clinical antitumor effects using two distinctive in vitro chemosensitivity tests: an analysis of true positive cases. 846 69

A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric cancer cell line, OCUM-2M/DDP, was established by chronic exposure of cells of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP at progressively increasing concentrations. The OCUM-2M/DDP cell line had an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromosome number and DNA index, suggesting that some alterations of the DNA in the CDDP-resistant cells had occurred. Neither the parent nor resistant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, the intracellular platinum content of OCUM-2M cells was significantly higher than that of OCUM-2M/DDP cells (51.9 +/- 1.8 vs 16.4 plus 1.0 ng/mg protein, mean +/- SD, respectively). The GSH levels in OCUM-2M cells and OCUM-2M/DDP cells were 3.5 +/- 1.0 micrograms/mg protein and 16.8 +/- 1.2 micrograms/mg protein, respectively. These levels were also significantly different. These findings suggest that the possible mechanisms of acquired resistance to CDDP in OCUM-2M/DDP cells may be a decrease in intracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/DDP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.
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PMID:Establishment of a cisplatin-resistant gastric carcinoma cell line OCUM-2M/DDP. 913 37


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