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)

Three cases of bile duct necrosis owing to hepatic arterial infusion chemotherapy (HAI) were reported. Regarding HAI, transcatheter hepatic arterial embolization (TAE) was applied in two cases (hepatocellular carcinoma: 1; metastasis: 1) and 5-fluorouracil (continuous) combined with leucovorin (one shot) therapy (LV + 5-FU) was given to one metastatic case. In the data of blood biochemistry, serum alkaline phosphatase, gamma-glutamyl transpeptidase, and leucine aminopeptidase values characteristically elevated without the elevation of total bilirubin value. Hepatic tumors degenerated with necrosis in all cases and no viable cells were histologically recognized. Although the destruction of bile ducts was locally detected adjacent to these tumors in TAE cases and was more widespread in the LV + 5-FU case, these lesions were very similar in each case. Therefore, we concluded that both ischemia and drug toxicity induced bile duct necrosis and the necrosis around the bile duct was the secondary change due to the leaked bile juice.
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PMID:[Bile duct necrosis and hepatic necrosis following hepatic arterial infusion chemotherapy]. 165 26

An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.
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PMID:Regulation of de novo and salvage pathways in chemotherapy. 187 99

Novel immunotherapeutic strategies for combating colon cancer are also being explored in pancreatic, hepatic, and esophageal cancers. Preliminary clinical trials in patients with pancreatic cancer suggest a therapeutic role for anti-idiotypic antibodies against tumor-specific monoclonal antibodies (MoAbs)--eg, CO17-1A, BW 494/32--but not for MoAbs when used alone. Adding low doses of interferon gamma to CO17-1A enhances in vitro antibody-dependent cellular cytotoxicity against pancreatic tumor cells; CO17-1A plus a regimen of 5-FU/doxorubicin/mitomycin has resulted in beneficial therapeutic effect. Treatments with immunotoxins, radiolabeled MoAbs, and adoptive immunotherapy are still being tested preclinically. In 105 patients with unresectable hepatocellular cancer, a 7% complete and 41% partial regression rate with 131I-labeled antiferritin has been reported. In several patients, radiolabeled antiferritin caused sufficient shrinkage of lesions to permit curative resection. Pretreatment with low-dose doxorubicin may improve the efficacy of low-dose radiolabeled antiferritin antibody therapy. Chemoembolization of primary hepatocellular carcinoma, based on the concept of regional therapy for metastatic colorectal cancer, has shown considerable palliative and survival benefit in patients with unresectable disease. Although adoptive immunotherapy has been used to treat hepatocellular carcinoma, the results have been disappointing. The development of immunotherapeutic approaches to esophageal cancer is less advanced than that for other gastrointestinal malignancies. Paralleling the successful use of 5-FU/interferon alfa-2a in colon cancer are two phase II studies that have evaluated this combination in patients with locally advanced esophageal cancer. The objective response rate (27%) was encouraging.
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PMID:Implications of current therapeutic approaches in colorectal cancer for other gastrointestinal malignancies. 199 29

Fifteen patients with advanced hepatocellular carcinoma were treated by hepatic arterial infusion (HAI). Treatment consisted of a 24-hour continuous HAI of etoposide (60 mg/day, day 1-5), CDDP (30 mg/day, day 1-5) and 5-fluorouracil (250 mg/day, day 1-26). Three patients had two series of infusions. Five patients were treated by transcatheter arterial embolization following HAI. Among 13 evaluable patients, one showed a complete remission and five patients had a partial response. We obtained a response rate of 46.2%. Toxicity included hematologic toxicity, alopecia, nausea and vomiting. The major toxicity was myelosuppression, but it was well tolerated. These results indicate that continuous HAI of etoposide, CDDP and 5-FU is effective for advanced hepatocellular carcinoma.
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PMID:[Hepatocellular carcinoma treated by continuous hepatic arterial infusion of etoposide, CDDP and 5-FU]. 215 70

A cooperative group study was carried out on the effect of Lipiodol transcatheter arterial chemo-embolization (L-TACE) for non-resectable hepatocellular carcinoma (HCC). Thirty-seven hospitals in Japan participated in this study and a total of 157 eligible patients included 138 males and 19 females with an average age of 60.3 y.o. In the chemo-embolization, Lipiodol mixed with 20-50 mg/m2 of doxorubicin (adriamycin) was given through a catheter, and this was followed by embolization with gelatin sponge. Effect of additional oral 5-FU (150-200 mg/day) was also studied as an open trial. Levels of serum alpha-feto protein decreased at 10 days after L-TACE, and this decrease lasted for 5 weeks. CR was observed in one patient, PR in 33, MR in 24, NC in 66 and PD in 16. The response rate was 24.3%. Cumulative one-year, two-year and three-year survival rates were 56.0%, 30.8% and 26.4%, respectively. It was concluded that higher survival rates after L-TACE were observed when (1) patients had better functional reserves of the liver, (2) HCC was in the less advanced stage and (3) L-TACE was carried out more than twice. A reduction of the tumor size after L-TACE did not necessarily mean a good prognosis for the patients. There was no significant difference in the survival rate between the patients taking or not taking 5-FU.
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PMID:[Lipiodol transcatheter arterial chemoembolization for non-resectable hepatocellular carcinoma--multicenter cooperative study]. 215 60

The objectives in administering anti-cancer therapeutics to the feeding artery of the tumor are to allow the agent to come in direct contact with the tumor cells, to lower the concentration of the agent in body circulation, to lessen the severity of side effects, and to augment efficacy of the agent. A remarkable partial regression was observed in two patients with advanced hepatocellular carcinoma, both at the stage in which surgical excision was diagnosed impossible; one was given successive and daily bolus administration of OH-1, a anti-tumor agent consisting of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon (nHulFN-alpha), and the other a successive and daily combined bolus administration of OH-1 and 5-FU. On investigating the role of the anti-cancer activity of OH-1 by analyzing the NK activity of rat liver large granular lymphocytes, we found that the NK activity was suppressed dose-dependently by nHuTNF-alpha, but not significantly. Thus, an increase in TNF dose in hepatic artery therapy seems undesirable from the standpoint of NK activity. The authors are presently carrying out investigations to elucidate the effector mechanism of the anticancer activity of OH-1.
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PMID:[Favorable response of advanced hepatocellular carcinoma to proper hepatic arterial administration of cytokines and the significance of the administration]. 245 70

Six cases of unresectable hepatic cancer in infant were treated with intra-arterial infusion therapy. The histological types were hepatoblastoma and hepatocellular carcinoma, 3 cases respectively. The clinical stages were 1 recurrent case in I, 1 in IIIA, 2 in IIIB and 2 in IV. Seldinger method and cannulation at laparotomy were employed in 4 cases and 2 cases, respectively. In the eldest case, a catheter with dual lumen reservoir developed in our department was inserted, making it possible to infuse drugs into hepatic artery and cutting off hepatic arterial blood flow temporarily. The anticancer drug used was ADM, CDDP, 5-FU, THP-ADM, and MMC; antiAFP-anticancer drug conjugate missile therapy was employed in 4 cases. According to image diagnosis, reduction or necrosis of tumor was observed in 5 cases. In all cases, AFP scores decreased. In 5 dead cases, 4 cases died of tumor enlargement (average survival time 16.3 months); 1 case died of DIC during chemotherapy. The other case could eventually undergo complete resection and is now alive. Intra-arterial infusion therapy seemed to be useful for patients of infant unresectable hepatic cancer.
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PMID:[Clinical study of intrahepatic arterial infusion of unresectable hepatoblastoma and hepatocarcinoma in children]. 247 63

Peripheral blood and tumor-infiltrating T lymphocyte subsets in BERH-2 hepatoma-bearing rats were investigated by indirect immunofluorescence stain and flow cytometry. Based on the above study, comparison of immunoregulatory action and inhibitory effect on the tumor were also done in vivo among several groups which received IFN, IL-2, 5-FU, combined immunotherapy (CI) or immunochemotherapy (IC), respectively. The results indicated that T lymphocyte subsets in hepatoma-bearing rats would undergo changes which were closely related with tumor growth and metastasis. IC had multiple phased advantages against the tumor, such as improving immunity, eliminating immunosuppression and directly killing the tumor cells. It is a valuable therapeutic regime in hepatoma.
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PMID:[Changes of T lymphocyte subsets in BERH-2 hepatoma-bearing rats and effect of different immunotherapies on the tumor]. 248 58

In a prospective clinical trial, 65 patients were studied in an investigation into the effects of the oral administration of 5-fluorouracil on resectable and non-resectable hepatocellular carcinoma. All patients had received initial treatment in the form of transcatheter arterial chemoembolization with adriamycin. No significant effect on the survival periods was demonstrated either in patients with resectable carcinoma or in those with non-resectable carcinoma, even though the survival rates were too high to reach an accurate conclusion (the lowest survival rate was 80%, 12/15, obtained in non-resectable carcinoma patients without 5-fluorouracil administration). 5-Fluorouracil administration did not significantly prolong the interval before recurrence in patients with resectable carcinoma (P = 0.139). However, its favorable effect on the interval up to disease progression was noted in patients with non-resectable carcinoma when a log-rank test was used to carry out a statistical analysis (P = 0.049), though it was not demonstrated by the Wilcoxon test (P = 0.102). Thus, adjuvant chemotherapy with 5-fluorouracil seems to have potential in the palliative effects of transcatheter arterial chemoembolization on non-resectable hepatocellular carcinoma, but further studies are necessary before a final conclusion can be reached.
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PMID:Studies on the chemotherapy with 5-fluorouracil in transcatheter arterial chemoembolization (TAE) treated patients with resectable or non-resectable hepatocellular carcinoma. Osaka Study Group on Hepatocellular Carcinoma. 253 62

In order to evaluate the combination therapy for liver and bile tract cancer, the effects of anticancer drugs and hyperthermia were observed using cultured human cancer cell lines. In the case of gall bladder cancer cell line (NOZ), combination of adriamycin and hyperthermia showed more effective inhibition for cell proliferation than MMC + hyperthermia and 5-FU + hyperthermia. Hepatocellular carcinoma cell line (JHH-4) showed remarkable inhibition of cell growth and secretion of albumin by combination treatment of adriamycin and hyperthermia. Morphologically, JHH-4 cells were enlarged and the nucleus was also enlarged with combination adriamycin and hyperthermia by phase contrast microscopy. Cytoskeleton of JHH-4 cells became irregular and intercellular borderline was unclear by plasma polymerization replica method (PPRM). The effects of BRM (OK-432 and TNF) on HCC cell lines was also investigated. OK-432 directly inhibited proliferation of JHH-4 cells. We observed internalization of OK-432 by JHH-4 cells with TEM and 16-mm movie. TNF showed various effects on human HCC cell lines. Proliferation of two cell lines was inhibited, and one tended to be enhanced after the addition of TNF to the medium. Hyperthermia influenced the effects of TNF to HCC cell lines. We think that this paper is a very significant study for improving the therapy for hepato-biliary cancers.
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PMID:[Combination therapy of hyperthermia and other methods in liver and bile tract cancers--evaluation of these methods using cancer cell lines in vitro]. 254 27


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