Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bestatin, one of the biological response modifiers (BRMs), is an inhibitor of aminopeptidase B (AP-B), leucine aminopeptidase (LAP) and aminopeptidase M (AP-M). In this report, we investigated the direct effect of bestatin on the growth of cancer cells in vitro using established four choriocarcinoma cell lines. In vitro chemosensitivity was evaluated by the succinate dehydrogenase inhibition (SDI) test. Bestatin showed the growth-inhibitory effect on all the choriocarcinoma cell lines dose-dependently, especially on NaUCC-4 cells. Both an isomer of bestatin with no inhibitory activity against aminopeptidases, (2R, 3S)-AHPA-(R)-Leu, and another isomer with stronger inhibitory activity against AP-B than bestatin, (2S, 3S)-AHPA-(R)-Leu, did not show growth inhibition on NaUCC-4 cells. So it is suggested that one of the possible mechanisms responsible for the direct action of bestatin on the choriocarcinoma cells may be related to the inhibition of activity of LAP or AP-M rather than that of AP-B. Furthermore, cytotoxicity of actinomycin D on the choriocarcinoma cells was significantly enhanced by combination with bestatin. These results suggest that bestatin has not only an indirect host-mediated anti-tumor activity, but also a direct growth-inhibitory effect on some kinds of cancer cell lines.
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PMID:Growth inhibitory effect of bestatin on choriocarcinoma cell lines in vitro. 178 99

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

A major problem associated with the succinate dehydrogenase inhibition (SDI) test using tetrazolium dye (MTT) as a cancer chemosensitivity testing is the contamination of non-malignant cells in the tumour tissues. Highly purified fresh human tumour cells from 44 solid tumours and 24 malignant ascites were used for the MTT assay. The purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients. The OD570 obtained from tumour cells alone was higher than that from non-malignant cells. The chemosensitivity of tumour cells was distinct from that of non-malignant cells. Moreover, the chemosensitivity of highly purified tumour cells was also distinct from that of non-purified cells just separated from tumour tissues. 31 of the 68 patients had evaluable lesions, and received cancer chemotherapy according to the results of MTT assay using highly purified tumour cells. A clinical response was obtained in 10 of the 31 patients (response rate = 32.3%, 5 complete responses, 5 partial responses).
Eur J Cancer 1991
PMID:Chemosensitivity testing with highly purified fresh human tumour cells with the MTT colorimetric assay. 183 95

The succinic dehydrogenase inhibition (SDI) test has been widely used to evaluate the sensitivity of cancer cells to anticancer agents. Recently, the techniques for tissue culture have progressed; the ability to make formazan has improved with the use of methylthiazol tetrazolium bromide (MTT) instead of triphenyl tetrazolium chloride (TTC) in this assay. Therefore, we modified the SDI test in order to evaluate the drug response to gastrointestinal cancer and applied it in a clinical study. In this assay, the optimal concentration levels of mytomycin-C and Adriamycin for the clinical materials are 10 micrograms/ml, that is, 10 times higher than for the cancer cell line, and that of Cisplatin is 30 micrograms/ml, for Cisplatin is unstable in the culture medium. To evaluate its antitumor effect, it was found necessary to expose the cancer cells to 5-fluorouracil (5-FU) for 3 days. We applied this assay for the clinical materials; the evaluable rate of this assay is 83.3%. The peculiarity of this assay is its high evaluable rate. These results suggest that this test may be useful for clinical application.
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PMID:A feasibility study of the SDI test for the evaluation of gastrointestinal cancer sensitivity to anticancer drugs. 190 38

A number of phenotypic abnormalities of the colorectal mucosa which appears normal have been described to be biomarkers of cancer development. To improve their sensitivity and specificity, we simultaneously determined 10 morphological and histochemical parameters in biopsies from the colonoscopically normal mucosa of the descending colon, sigmoid, and rectum. The results were analysed by multivariate statistical methods. We tested the discriminating power of proliferative, morphometric, enzyme and mucin histochemical parameters from 80 patients either at average risk (controls), with an increased risk for colorectal carcinoma (high-risk), or with a manifest carcinoma. The following parameters were investigated: number of mitotic figures per crypt, crypt length, apical, medial and basal crypt diameter, crypt surface, activity of succinate dehydrogenase (EC 1.3.99.1), activity of acid beta-galactosidase (EC 3.2.1.23), sulpho- and sialomucin contents. Univariate statistical analyses revealed that crypt length, crypt diameter and crypt surface were significantly increased in the high-risk group, the carcinoma carriers having intermediate values between average-risk and high-risk patients. In a two-group discriminant analysis, high-risk or carcinoma patients could be separated from average-risk patients with a sensitivity of 92.9% and a specificity of 100%. When the analysis was repeated for three groups (carcinoma carriers separated from high-risk patients), sensitivity and specificity were 100% for each group. We conclude that identification of patients at risk for colorectal carcinoma is possible from the normal-appearing left colonic and rectal mucosa by morphometric and cytochemical analysis of biopsies.
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PMID:Identification of patients at high risk for colorectal carcinoma from biopsy studies of the apparently normal colorectal mucosa. A multivariate analysis. 190 33

Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t-test). These results indicate increased entrapment of tumour cells in the pulmonary microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex.
Br J Cancer 1991 Sep
PMID:Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved. 191 Nov 92

The feasibility of a combined chemotherapy using dipyridamole (DP) with adriamycin (ADM) and 5-fluorouracil (5-FU) was investigated. First, the chemosensitivity of gastric cancer tissues was determined by the succinate dehydrogenase inhibition test, which showed sensitivity to ADM and 5-FU is increased by DP. Next, a clinical trial of combined therapy of DP, ADM and 5-FU, as a post-operative adjuvant chemotherapy for gastric cancer patients, was performed. DP (50 mg) was given as a 1-h i.v. infusion, and ADM (20 mg) was given as a single i.v. injection. This treatment was started on post-operative day 10, and was repeated every 2 weeks. Simultaneously with these treatments, DP (300 mg) and 5-FU (150 mg) were administered post-operatively daily. A total of 63 courses of therapy in nine patients were performed. The adverse effects related to the DP infusion were flushing, headache, nausea and upper abdominal discomfort, all of a low grade. DP did not appear to alter the toxicity of ADM and 5-FU, and no severe adverse effect was noted for this combination therapy. The pharmacokinetics of DP were also investigated in five patients. The mean plasma concentration of DP increased 4.41 micrograms/ml and remained above 0.25 microgram/ml for over 6 h. This combination chemotherapy appears to be safe and may be useful clinically in treating cancer.
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PMID:Dipyridamole combination chemotherapy can be used safely in treating gastric cancer patients. 195 58

The in vitro succinate dehydrogenase inhibition (SDI) test was adapted to be used with microtiter plates and this microtiter SDI (mSDI) test was evaluated for clinical use of chemosensitivity testing, as compared to findings with the SDI test. The optimal conditions of the mSDI test were determined: (1) 2-5 x 10(4) cells/well; (2) enzymatic disaggregation of solid tumors with the use of a mixture of 0.2% pronase, 0.25% collagenase, 0.1% DNase for 20 min at 37 degrees C; (3) addition of 10 mM sodium succinate in the colorimetric reaction; and (4) use of dimethyl sulfoxide (DMSO) as a solvent for extraction of formazan product. Good correlations were observed between the mSDI and the SDI tests when S-180 cells (r = 0.890-0.996) or 16 human fresh tumor cells (r = 0.731-0.999) were exposed to six anti-cancer drugs (carboquone, adriamycin, mitomycin C, aclacinomycin A, cisplatin, 5-fluorouracil). Thus, the mSDI test facilitates testing of a large number of drugs with minimal amounts of specimens, and is expected to replace the SDI test for chemosensitivity testing of clinical tumor cells.
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PMID:The microtiter SDI test is more advantageous than the SDI test for assessing the chemosensitivity of human tumor cells. 195 59

The activity of the mitochondrial glycerol phosphate dehydrogenase (EC 1.1.99.5), the enzyme unique to the glycerol phosphate hydrogen shuttle, was measured in normal human tissues and tumors and compared with the activity of succinate dehydrogenase, another enzyme that transfers electrons to ubiquinone at site II of the electron transport chain. Six of 7 insulinomas and 10 of 12 carcinoid tumors showed high glycerol phosphate dehydrogenase activity. The activity was also increased in 3 of 4 gastrinomas, 2 paraganglionomas, 1 of 4 thyroid nodules, and 1 parathyroid tumor. These tissues belong to the amine precursor uptake decarboxylation system. The activity of glycerol phosphate dehydrogenase was generally unremarkable in non-amine precursor uptake decarboxylation system tumors and in normal tissues studied. However, 1 of 2 breast carcinomas, 1 submandibular tumor, and 2 of 3 melanomas were enriched in glycerol phosphate dehydrogenase activity. In general, succinate dehydrogenase activity exceeded that of glycerol phosphate dehydrogenase in all tissues except some of the tissues in which glycerol phosphate dehydrogenase activity was high. Normal tissues, such as the pancreatic beta-cell, which aerobically metabolize glucose rapidly utilize the glycerol phosphate shuttle to oxidize the large amount of NADH formed from glucose metabolism in the cytosol. Whether this is the reason for the enriched activity of the glycerol phosphate dehydrogenase in certain amine precursor uptake decarboxylation system tumors is unknown.
Cancer Res 1990 Nov 15
PMID:High activity of mitochondrial glycerol phosphate dehydrogenase in insulinomas and carcinoid and other tumors of the amine precursor uptake decarboxylation system. 197 16

In order to determine the most effective anticancer agent for individual human tumor, we have performed several chemosensitivity tests, such as human tumor clonogenic assay (HTCA), succinic dehydrogenase inhibition test (SDI-T), nude mouse isotope assay (NM-IA) and subrenal capsule assay (SRCA). In this study, an novel in vitro chemosensitivity test (ATP-assay) measuring ATP amounts of cancer cells was carried out in 69 fresh gastro-intestinal tumors obtained at surgery. As the results, the evaluable rate of ATP assay was 87.0%. The positive rate of ATP assay against all tumors were 13.3% in mitomycin-C (MMC), 11.7% in adriamycin (ADM), 13.3% in 5-fluorouracil (5-FU) and 18.3% in cis-diamminedichloroplatinum (CDDP), respectively. Overall predictive accuracy rate was 82.8%. The comparative study of the survival rates of the patients with stage IV gastric cancer, receiving sensitive anticancer agents assayed by ATP assay, and those receiving negative anticancer agents revealed that the survival rate of the patients treated with sensitive drugs was longer with Kaplan-Meier analysis. From these results, it seems reasonable to conclude that ATP assay is of value in determining the chemosensitivity of gastrointestinal cancer in each patient.
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PMID:[Clinical studies of in vitro chemosensitivity test evaluated by ATP assay of gastrointestinal cancer]. 212 11


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