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)

Photodynamic therapy consists of the systemic administration of a derivative of haematoporphyrin (Photofrin II) followed 24-72 h later by exposure of malignant lesions to photoradiation. We investigated the efficacy of this treatment after direct intratumoral injection of Photofrin II. This direct treatment regimen resulted in higher rates of inhibition of mitochondrial cytochrome c oxidase (5.13% J-1 cm-2 x 10(-1) and succinate dehydrogenase (3.14% J-1 cm-2 x 10(-1] in vitro at 2 h after intratumoral injection compared to rates of inhibition obtained after intraperitoneal drug administration: 0.51 and 0.42% J-1 cm-2 x 10(-1), respectively. A significant delay in tumour growth in vivo was observed in animals that received intratumoral injections 2 h before photoradiation compared to animals injected intraperitoneally at either 2 or 24 h before photoradiation. The treatment protocols were compared with control groups, consisting of Photofrin II administration intratumorally or intraperitoneally without photoradiation, or photoradiation in the absence of Photofrin II. These data indicate that the intratumoral injection regimen with Photofrin II enhanced the efficacy of photodynamic therapy. The greater delay in tumour growth observed after intratumoral administration of Photofrin II suggests a mechanism favouring direct cell damage.
Br J Cancer 1990 Apr
PMID:Increased efficacy of photodynamic therapy of R3230AC mammary adenocarcinoma by intratumoral injection of Photofrin II. 213 78

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) was associated with the development of hepatitis, foci of altered hepatocytes and hepatocellular adenomas and carcinomas. The cytomorphological and cytochemical analysis permitted the identification of three different types of focal lesions; namely, glycogen-storage foci, mixed-cell foci and intermediate-cell foci, each showing a characteristic pattern. The cells of the glycogen-storage foci had clear to acidophilic cytoplasm, and were overloaded with glycogen. They showed a marked elevation in the activity of glucose-6-phosphate dehydrogenase (G6PDH) and malate dehydrogenase (MDH), increased activity of succinate dehydrogenase (SDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycerol-3-phosphate dehydrogenase (G3PDH), reduction in the activity of glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and adenyl cyclase (ADC), and unchanged activity of glycogen synthase (SYN) and gamma-glutamyl transferase (GGT). The mixed-cell foci mainly consisted of basophilic cells poor in glycogen, but were intermingled with cells containing glycogen. These foci were characterized by a marked decrease in activity of PHO, SYN, G6Pase, G6PDH, ATPase and ADC, and increased activity of GGT, SDH, MDH and GAPDH. The intermediate-cell foci consisted of cells with both basophilic and glycogenotic cytoplasmic compartments, and showed a similar enzyme histochemical profile to the mixed-cell foci, with slight differences in the degree of elevation or reduction of some enzymes. The phenotypic similarities and the close spatial relationship between the foci of altered hepatocytes, and the hepatocellular adenomas and carcinomas in WHV-infected woodchucks, suggest that these lesions are preneoplastic. The focal morphological and metabolic aberrations emerging during hepatocarcinogenesis in WHV-infected woodchuck, are in principle similar to those identified in the course of chemical hepatocarcinogenesis in various species. The focal metabolic aberrations apparently represent a general biological response of the liver parenchyma to oncogenic agents and are closely linked to neoplastic transformation of the hepatocytes.
J Cancer Res Clin Oncol 1990
PMID:Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus. 215 41

Merocyanine 540 (MC 540) is a photosensitizing dye that is used clinically for the purging of autologous bone marrow grafts and preclinically for the inactivation of enveloped viruses in blood products. Its mechanism of action is not yet well understood. This paper investigates the sites of MC 540-mediated photodamages in L1210 leukemia cells by examining the effects of MC 540-sensitized photoirradiation on several soluble and membrane-bound marker enzymes. When exposed to MC 540 and white light under a standard set of conditions, the activities of Na+/K(+)-ATPase, Mg2(+)-ATPase, and 5'-nucleotidase (three plasma membrane-bound enzymes) were reduced by 54, 49, and 55%, respectively. None of the intracellular enzymes included in this survey was affected by MC 540-sensitized photoirradiation as long as the plasma membrane remained intact. The two soluble enzymes, lactate dehydrogenase and malate dehydrogenase, remained refractory to MC 540-sensitized photoirradiation even after the plasma membrane had been disrupted. By contrast, the activities of the membrane-bound enzymes, NADPH-cytochrome c reductase and succinate dehydrogenase, were reduced in cell lysates by 55 and 81%, respectively. Purified NADPH-cytochrome c reductase was about 3 times less sensitive than the microsomal enzyme, suggesting that the membrane environment facilitated photoinactivation. The MC 540-sensitized photoinactivation of enzymes was accelerated in the presence of deuterium oxide and inhibited if oxygen in the medium was displaced by nitrogen or azide was added to the medium. Taken together, these data support the view that the plasma membrane is a major target of MC 540-mediated photodamages, that the inactivation of membrane-bound enzymes is an oxidative process, and that at least some photodynamic damages are mediated by type II chemistry.
Cancer Res 1990 Dec 15
PMID:Merocyanine 540-sensitized photoinactivation of soluble and membrane-bound enzymes in L1210 leukemia cells. 217 31

The triarylmethane derivative Victoria Blue-BO (VB-BO) and the chalcogenapyrylium (CP) dyes have potential for use in photochemotherapy, because they are taken up by the mitochondria of malignant cells and cause cell death. To clarify the mechanism of cell killing we examined the phototoxic effects of VB-BO and a series of three CP dyes on bioenergetic function in isolated rat liver mitochondria. Without photoirradiation, and irrespective of the respiratory substrate used, each of the compounds tested induced some uncoupling of oxidative phosphorylation. Visible irradiation of VB-BO produced an inhibition of mitochondrial respiration when glutamate plus malate, but not succinate, was used as the respiratory substrate. With photoirradiation VB-BO was also shown to inhibit rotenone-sensitive NADH-cytochrome c reductase activity, but it had no effect on succinate-cytochrome c reductase activity. These data indicate that photoactivation of VB-BO produces selective inhibition of mitochondrial respiratory complex I. Photoirradiation of the CP dyes inhibited both complex I and complex II initiated respiratory activity. With photoirradiation, the CP dyes also inhibited both NADH- and succinate-cytochrome c reductase activities, as well as other membrane-bound enzymes, cytochrome c oxidase and succinate dehydrogenase, but not the mitochondrial matrix enzyme, citrate synthetase, or the cytosolic enzyme, lactate dehydrogenase. alpha-Tocopherol protected bioenergetic activities against CP dye photodamage. These results suggest that mitochondrial photosensitization by CP compounds is mediated by the production of membrane-damaging singlet oxygen which causes nonspecific damage to membranes and membrane-bound enzymes.
Cancer Res 1990 Dec 15
PMID:Mitochondrial toxicity of cationic photosensitizers for photochemotherapy. 217 36

The chemosensitivities of 42 human head and neck squamous cell carcinomas were examined using the in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at surgery or biopsy were exposed to five different antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5-fluorouracil (5-FU), and 1-hexylcarbamoyl-5-fluorouracil (HCFU). The results were analyzed according to the histopathologic degree of differentiation of well, moderately, and poorly differentiated squamous cell carcinoma. The average decrease in succinate dehydrogenase activity was 43.2 +/- 24.9 for ADM, 29.0 +/- 14.2 for CDDP, 32.9 +/- 17.6 for CQ, 64.2 +/- 20.6 for 5-FU, and 26.8 +/- 16.9 for HCFU. There was a statistically significant difference in the decrease of succinate dehydrogenase activity between well and poorly differentiated squamous cell carcinomas. These data suggest that, for patients with a poorly differentiated squamous cell carcinoma, the response to anti-cancer drugs may be more satisfactory than in those with a well-differentiated squamous cell carcinoma.
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PMID:Histologic differentiation and chemosensitivity of human head and neck squamous cell carcinomas. 221 Nov 1

The cancer chemotherapeutic efficacy of 3,4-dihydroxybenzylamine (DHBA), a dopamine analog with reduced neurotoxic effects, was evaluated in strain A mice bearing transplantable Ehrlich's ascites carcinoma. The analog was administered intraperitoneally on day 1 post-transplantation at dose schedules of 50, 100 and 200 mg/kg/day for 7 consecutive days. The results demonstrated a significant inhibition of tumor growth and prolongation of the survival time of EAC tumor bearing mice following DHBA treatment. Diminished activity of the growth-related respiratory enzyme succinate dehydrogenase along with the stimulated activity of the lysosomal enzyme beta-glucuronidase in the DHBA-treated tumor cells indicated inhibition of tumor growth as well as active lysis of the tumor cells. Tumor inhibition was accompanied by marked improvements in hemoglobin concentration. RBC count and bone marrow cellularity. The results demonstrated that DHBA did not adversely affect hematological profile of the host while it inhibited the growth of Ehrlich's ascites carcinoma.
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PMID:Tumor inhibition and hematological improvements by dopamine analog 3,4-dihydroxybenzylamine in mice bearing transplantable carcinoma. 223

In vitro chemosensitivity was evaluated in 28 patients with head and neck squamous cell carcinomas (12 pharyngeal cancers, 7 oral cavity cancers, 4 laryngeal cancers, 4 maxillary sinus cancers and 1 esophageal cancer) and 19 patients with thyroid cancer. Tumor fragments obtained at biopsy or surgery were exposed to anticancer drugs and assayed for succinate dehydrogenase (SD) activity. The average of SD activity in squamous cell carcinomas was 63.2% for 5-FU, 24.6% for HCFU, 26.1% for CDDP, 41.0% for ADM, 28.4% for THP-ADM, 27.1% for ACR, 27.4% for CQ and 45.3% for VLB. In thyroid cancers, the average SD activity was 73.9% for 5-FU, 16.7% for HCFU, 32.6% for CDDP, 48.3% for ADM, 38.3% for THP-ADM, 57.3% for ACR, 39.0% for CQ and 75.3% for VLB. The SD activity inhibition rate by anticancer drugs was larger in cases of head and neck squamous cell carcinomas than in cases of thyroid cancers except for HCFU. Higher sensitivity to each antitumor drug detected in cancer tissues from metastatic lymph-nodes than in tissues from primary lesions needs further investigation.
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PMID:[Chemosensitivity testing of anticancer agents in head and neck tumors. I: Comparison between head and neck squamous cell cancers and thyroid cancers]. 229 40

The sensitivity to heat and radiation of 22 rectal cancer tissues obtained at biopsy was studied using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase activity of tissue fragments was assayed after exposure at 43 degrees C (hyperthermia) for 20 hours, to radiation of 6 Gy, and to both heat (43 degrees C) and radiation (6 Gy). The sensitivity to each treatment was estimated by the percentage of succinate dehydrogenase activity of the treated cells compared with that of control cells. The mean plus or minus standard deviation of succinate dehydrogenase activity after exposure to radiation, heat, and both heat and radiation, was 84.7 +/- 12.6 percent, 52.9 +/- 20.7 percent, and 46.8 +/- 20.7 percent, respectively. The succinate dehydrogenase activities of heat-treated cells and both heat- and radiation-treated cells were significantly lower than that of the radiation-treated cells (P less than 0.01). The succinate dehydrogenase activities of heat plus radiation treated cells were the lowest in tissues from cancer lesions. Although the number was small, there was a correlation between this test and clinical outcome in seven of nine cases. Thus, preoperative therapy of hyperthermia plus radiotherapy is expected to be effective for treating patients with rectal cancer.
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PMID:Sensitivity to heat and radiation of human rectal malignant tissues in vitro. 236 27

The sensitivity to 5-fluorouracil (5-FU) was examined in 40 well differentiated and 50 poorly differentiated gastric cancer tissues and 15 normal tissues, using the in vitro succinate dehydrogenase inhibition (SDI) test. The tissue phosphorylating and degrading activities of 5-FU were compared in each type of tumor and in the normal tissues. Decreases in succinate dehydrogenase (SD) activity were more apparent in the poorly differentiated cancer tissues than in the well differentiated cancer tissues (p less than 0.005), and than in the normal tissues (p less than 0.001), exposed to 5-FU. The rate of sensitivity to 5-FU was higher in the poorly differentiated than in the well differentiated tissues and than in the normal tissues. The phosphorylating activities of 5-FU, in pathways involving uridine (Urd) phosphorylase and Urd Kinase, and thymidine (dThd) phosphorylase and dThd Kinase, were 1.7 fold higher in the poorly differentiated than in the well differentiated tissues and several fold higher than in the normal tissues (p less than 0.05-p less than 0.001). The degrading activity of 5-FU was similar in both types of tumor and in the normal tissues. Our findings show that 5-FU is actively metabolized to 5-FU-nucleotides in poorly differentiated tissues after incorporation into the tumor cells. 5-FU seems to have an increased susceptibility in cases of poorly differentiated gastric carcinoma.
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PMID:5-Fluorouracil is converted to F-nucleotides more extensively and is more cytotoxic in poorly differentiated than in well differentiated human gastric carcinoma. 238 81

Chronic administration of the estrogen 17 beta-estradiol induces kidney tumors in male Syrian hamsters within 6 months of initial exposure. Although these tumors have previously been studied histologically and histochemically and have been postulated to be derived from proximal tubular and/or interstitial cells, there exists no unambiguous evidence for an epithelial or mesenchymal origin. To elucidate the histogenesis of these neoplasms, kidney sections of hamsters treated with estradiol for 4, 5, and 6 months and age-matched untreated controls were investigated histologically and histochemically. Proliferating foci were observed in kidneys exposed to estradiol for 5 and 6 months. They consisted of clusters of spindle-shaped cells forming solid blocks, cords, or branches located between tubules. These foci were judged to be precursors of larger tumors identified in the latter treatment group. The histological and histochemical profile of foci and tumors matched closely. These lesions were marked by very high activities of alkaline phosphatase, adenyl cyclase, and glucose 6-phosphate dehydrogenase. In contrast, glycogen content and activities of glucose 6-phosphatase, succinate dehydrogenase, and gamma-glutamyl transpeptidase were low or absent. Immunofluorescence of the intermediate filaments revealed that foci and tumors solely expressed vimentin and desmin but not cytokeratin. The morphology, enzyme histochemical pattern, and immunofluorescence strongly support a mesenchymal origin of the estradiol-induced hamster kidney tumors studied. The neoplasms were probably derived from vascular smooth muscle cells of a cell subtype particularly sensitive to hormonal stimulation and transformation.
Cancer Res 1988 Feb 15
PMID:Histochemical analysis of the development of estradiol-induced kidney tumors in male Syrian hamsters. 244 29


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