Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed in vitro resistance to 4'-epidoxorubicin (Epi-A) and cis-dichlorodiammineplatinum (cis-DDP) in one rat (MH1C1) and one human hepatoma cell line (HepG2). When compared to their parental cells, the Epi-A resistant rat cells were 17 times and the resistant human cells 27 times more resistant to Epi-A in terms of GI50 in the cell growth inhibition assay. The cis-DDP resistant rat cells were 20 times and the resistant human cells 12 times more resistant to cis-DDP. Cross-resistance to cis-DDP was observed in the Epi-A resistant rat cells but not in the human cells. The multidrug resistant gene product, GP 170, was markedly expressed in both Epi-A resistant substrains compared with their parent lines, suggesting a role of this protein in the development of resistance to Epi-A. Cadmium-binding proteins of metallothionein (MT) size bound 52% of cytosolic 109cadmium in the cis-DDP resistant human cells compared with 8% in the parental cells. This may indicate that these proteins contribute to the observed cis-DDP resistance.
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PMID:Induction of in vitro resistance to 4'-epidoxorubicin and cis-dichlorodiammineplatinum in hepatoma cells. 167 81

The chemosensitivity was evaluated by the in vitro succinate dehydrogenase inhibition (SDI) test in 1,000 human tumors including 237 gastric cancers, 116 colorectal cancers, 113 hepatoma and 534 others. These tumor cells were exposed to 5 kinds of antitumor drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cis-platinum (DDP). After exposure to the antitumor drugs, cell viability was assessed with colorimetric assay, based on the ability of succinate dehydrogenase (SD) in living tumor cells to reduced a tetrazolium (MTT) to a formazan. The chemosensitivity was determined to be positive when the SD activity of drug exposed cells decreased to below 50% of that of control cells, on day 3 of exposure. The chemosensitivity varied in the tumor tissues. The chemosensitivity of metastatic lesions of lymph nodes were higher than that of the primary lesions, while metastatic liver tumors had lower sensitivity than the primary lesions. The intra-tumorous distribution of SD activity in 12 human gastric cancers were compared with normal adjacent tissues using histochemistry. Seventy-five % (9/12) of gastric cancer tissues had higher SD activity than normal adjacent tissues. The SDI test is rapid and simple method to predict the sensitivity test of various human tumors to antitumor drugs.
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PMID:[The sensitivity of 1,000 human tumors to antitumor drugs using the succinate dehydrogenase inhibition (SDI) test]. 227 70

The in vivo cross-linking of cytokeratins to DNA in intact Novikoff ascites hepatoma cells exposed to the chromium salt K2CrO4 and cis-diamminedichloroplatinum(II) (cis-DDP) was studied. Cytokeratin-DNA complexes were obtained by high-speed centrifugation of cells solubilized in buffered 4% sodium dodecyl sulfate. The cytokeratins were identified electrophoretically and immunologically by use of polyclonal and monoclonal antibodies. Time dependence experiments showed that detectable cross-linking occurred after cells were exposed to K2CrO4 for at least 4 h, and the amount of keratin-DNA complexes increased with the incubation time. Each of the three Novikoff ascites hepatoma cytokeratins (p39, p49, and p56) showed a different apparent rate of cross-link formation with DNA. Cytokeratin-DNA complexes were detectable in our system only with K2CrO4 concentrations of 200 microM or greater, and saturation in cross-linking was effected at approximately 2 mM. Higher K2CrO4 concentrations (up to 5 mM) did not produce further significant increases in the amount of cross-linked cytokeratins. Chromium and cis-DDP cross-linked the same cytokeratins at approximately the same ratios; however, both agents cross-linked the major cytokeratins selectively, since not all cytokeratins present in Novikoff hepatoma cell lysates could be cross-linked to DNA. Further evidence of DNA-cytokeratin complexes was obtained by CsCl gradient centrifugation. Our results document the ability of chromate and cis-DDP to produce DNA-cytokeratin cross-links in vivo and show that in live Novikoff hepatoma cells some, but not all, of the components of intermediate filaments are within cross-linking distance of DNA.
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PMID:Cross-linking of cytokeratins to DNA in vivo by chromium salt and cis-diamminedichloroplatinum(II). 242 Mar 55

When Novikoff hepatoma-bearing rats were given injections of a therapeutic dose of cis-diamminedichloroplatinum(II) (cis-DDP) (7 mg/kg), DNA-protein cross-links could be detected by using antisera to dehistonized chromatin, nuclear matrix, or Novikoff hepatoma cytoskeletal preparation. The extent of cross-linking increased in time up to 24 h after the injection, after which time the DNA-protein cross-links were gradually repaired, with no cross-links detectable at 72 h. trans-DDP in equitoxic (40 mg/kg) dose was very efficient in forming DNA-protein cross-links. Although formed more rapidly, these trans-DDP-mediated cross-links were repaired faster, within 48 h after the injection. The repair of cross-links at equimolar trans-DDP dose (7 mg/kg) was even more rapid. The principal proteins cross-linked to the DNA by both cis- or trans-DDP were Novikoff hepatoma cytokeratins (Mr 39,000, 49,000, 56,000, and an additional protein band reacting with the antiserum to Novikoff hepatoma cytoskeletal preparation at Mr approximately 68,000).
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PMID:In vivo DNA-protein cross-linking by cis- and trans-diamminedichloroplatinum(II). 243 63

Ten consecutive adults with localized nonresectable hepatocellular carcinomas were selected as a nonrandom sample for an investigation into the effectiveness of cisplatin (DDP) as a single agent when administered regionally via the hepatic artery from 1981 to 1984. The dose of DDP was 50 mg/m2 (normally, 80 mg). Complete remission (CR) was observed in one patient, partial remission (PR) in three patients, and in five patients, there were no significant changes in tumor size; the disease progressed in one patient. The mean period of survival of the group was 19.7 months. All patients suffered from severe nausea and vomiting, ordinarily until the afternoon of the day after treatment. One patient died of uremia, which related to the cytostate. The authors consider cisplatin useful in the intra-arterial treatment of hepatocellular carcinoma with favorable prognostic factors in patients for whom surgical treatment is not suitable.
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PMID:Regional intra-arterial infusion of cisplatin in primary hepatocellular carcinoma. A phase II study. 302 14

There was no direct inhibition of DNA synthesis in ascites hepatoma 22A cells after intraperitoneal injection of single doses of copper (II) complexes with amino acids into tumor-bearing C3HA mice. Meanwhile cis-dichlorodiamine platinum (II) (DDP) as well as sarcolysine showed such inhibition. Copper (II) complexes with alpha-amino acids displayed as significant superoxide dismutase-like activity at concentrations corresponding to therapeutic doses of these compounds. The complexes of copper (II) combined with DDP give an additive antitumor effect in solid tumors of mice.
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PMID:[Characteristics of the mechanism of action of complex copper (II) compounds with alpha-amino acids]. 403 65

Thirty patients with metastatic malignancy of various types were treated with cis-diamminedichloroplatinum(II) (DDP) administered by continuous infusion for 120 hours. The starting dose was 20 mg/m2/day (100 mg/m2/course) and was escalated by stages to 40 mg/m2/day (200 mg/m2/course). Dose-limiting toxicity was observed at 30 mg/m2/day (150 mg/m2/course), manifested as marrow suppression and particularly thrombocytopenia in 13 of 14 patients evaluated at doses greater than or equal to 30 mg/m2/day. The gastrointestinal toxicity characteristic of bolus treatment schedules was less intense but was cumulative and dose-related. Renal toxic effects developed in five of 30 patients in spite of adequate hydration and daily diuretic therapy. Peripheral neuropathy developed in the only two patients who received four courses of continuous-infusion DDP. Antitumor effects were observed in six patients (oral cancer, two; lymphoma, one; prostatic cancer, one; hepatoma, one; and bronchogenic carcinoma, one). The recommended starting dose for continuous venous infusion therapy with DDP is 30 mg/m2/day for 5 days.
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PMID:Phase I study of cis-diamminedichloroplatinum(II) administered as a constant 5-day infusion. 625 73

Patients with unresectable liver cancer (primary and metastatic) were treated with a newly-devised arterial infusion chemotherapy using Cis-DDP and its antidote Sodium thiosulfate (STS). The patients consisted of 4 with primary hepatoma and 1 with metastatic liver cancer originated from intestinal cancer. For the purpose of reducing unfavourable side effects without changing anticancer effect, Cis-DDP was infused into hepatic artery through the catheter while STS being administered systemically. According to Koyama and Saito's criteria, 2 of 5 patients showed partial response (PR) and the others showed no change (NC). The median survival time after onset of therapy was 6.6 months ranging from 2 to 11 months in all the patients. The myelosuppression and renal toxicity, which were considered to be the most serious side effects of Cis-DDP, were not found and liver function was not affected in all the patients. However, all the patients complained of nausea and vomiting. Thus, our experience has indicated that this newly devised infusion chemotherapy is a promising method for treating unresectable liver cancer, although further efforts are necessary for reducing the gastrointestinal toxicity.
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PMID:[Intra-arterial infusion through 2 routes in liver (primary and metastatic cancer]. 668 85

We studied the effects of combination chemotherapy of an antitumor drug cis-diamminedichloroplatinum (II) (DDP) and its potent antidote, sodium thiosulfate (STS) in rat liver tumor systems. This therapy was given to female WKA rats with metastatic liver tumors 13 days after inoculation of syngeneic hepatoma cells through the mesenteric vein. DDP and STS were administered via two different routes, hepatic artery and femoral vein, respectively (we call this treatment "two route infusion chemotherapy"). The antitumor effects were evaluated 21 days after the treatment by calculating the tumor weight from the total weight of the liver. Tumor weights of rats treated with 20 mg/kg of intra-arterial DDP plus 1,054 mg/kg of systemic STS (group A), 5 mg/kg of intra-arterial DDP alone (group B), and 5 mg/kg of systemic DDP alone (group C) were, about one fifth, two fifths and three fifths of the tumor weights in the untreated controls, respectively. In group A, no rats died despite administration of a 4-fold higher DDP dose than in the latter two groups B and C in which 14-18 per cent of the rats died, due to DDP-induced toxicity. The patterns of body weight gain in the three groups after the chemotherapy were much the same. Our results clearly indicate that the antitumor effect of DDP on metastatic liver tumors in rats can remarkably be enhanced by the "two route infusion chemotherapy" of DDP and STS.
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PMID:"Two route infusion chemotherapy" using cis-Diamminedichloroplatinum (II) and its antidote, sodium thiosulfate, for metastatic liver tumors in rats. 689 49

The antimetastatic effects of two drugs, cis-diamminedichloroplatinum(II) (DDP) and hydrocortisone (liposome-incorporated or free), were studied. The experimental models were regional and distant metastases of hepatoma A and pulmonary adenocarcinoma, which were transplanted into the footpads of A/He mice. Liposomes were prepared from phosphatidylcholine by sonic dispersion. DDP and hydrocortisone were injected sc into the region of the plantar aponeurosis of the foot with the primary tumor. This administration route was considered to be equivalent to the intralymphatic route. Evidence indicated that only liposome-incorporated DDP and hydrocortisone decreased significantly the frequency and growth rate of tumor metastases in the regional lymph nodes. The effect observed was not due to the direct action of the drugs on the primary tumors. When nonencapsulated, these drugs were ineffective. Both liposome-encapsulated and free DDP did not affect distant metastases of pulmonary adenocarcinoma. The intralymphatic administration of liposome-encapsulated antitumor agents is suggested as a method for the prophylactic treatment of tumor metastases in the lymph nodes.
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PMID:Intralymphatic administration of liposome-encapsulated drugs to mice: possibility for suppression of the growth of tumor metastases in the lymph nodes. 693 32


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