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: UMLS:C0019204 (hepatocellular carcinoma)
71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 54 patients who underwent hepatic artery infusion chemotherapy for hepatic tumors at our hospital between January 1990 and December 1996, we investigated the complications of this therapy and the therapeutic techniques following its discontinuation. The arterial infusion was discontinued in 36 of the 54 patients; 13 due to death (mean survival period: 15.7 months), and 23 in whom occlusion of the reservoir, etc. made it impossible to use arterial infusion (mean period of use: 13.8 months), and the minimum duration of use was 41 days and maximum duration of use 992 days. The most common complication of the reservoir hepatic artery infusion was reservoir occlusion (14.8%). Another serious complication was reservoir deviation outside the blood vessel in two patients; deviation in to the gastric lumen in one case and intraperitoneal deviation in the other. Four hepatocellular carcinoma patients, in whom it became impossible to use the reservoir due to its occlusion, underwent re-hepatectomy. Three of them survived for more than two years following supplemental local therapy, including subarterial injection, TAE, PEIT, microwave tumor coagulation (MTC). Of four patients with colon cancer metastasizing to the liver, one could undergo re-hepatectomy, one received subarterial injection, and two have survived without relapse. Two of three patients with breast cancer underwent systemic chemotherapy and endocrine therapy successfully, while the third one underwent subarterial injection and TAE, and is still under observation. Hepatic artery infusion should sometimes be discontinued owing to complications caused by various factors. Even if it becomes impossible to use the reservoir, local therapeutic techniques, including re-hepatectomy, TAE, PEIT, MTC, etc., may be performed in some patients. These findings suggest that it is necessary to review the interdisciplinary treatment so as to be appropriate to the primary disease.
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PMID:[Complication of reservoir hepatic artery infusion chemotherapy and additional treatments]. 938 47

Zymosan, a non-specific macrophage-stimulating agent, modifies favourably tumour growth in the liver but has minor effect on renal tumours. The mechanism accounting for variation is still to be clarified. The effect of zymosan on liver cancer may be mediated by the macrophage-monocyte system. Kupffer cells are in vitro cytotoxic against colon cancer cell lines. The kidney is sparse in macrophage elements. The prostaglandin synthesis inhibitor, indomethacin, inhibits tumor growth. In Wistar-FU rats inoculated in the liver and the kidney with an adenocarcinoma cell suspension, pretreatment with zymosan (3 mg x 100 g[-1]) significantly reduced both tumour take and liver volume. This effect was attenuated by concomitant administration of indomethacin (0.2 mg x 100 g[-1]). After 2 weeks there was still reduced liver tumour volume. No significant effects on tumour take or growth were observed when the cells were inoculated into the kidney. There was no significant effect of zymosan on an hepatoma in Lister-Hooded rats. Pretreatment with indomethacin had no effect on tumor take or initial growth.
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PMID:The influence of zymosan and indomethacin on liver and kidney tumor growth. An experimental study in rats. 938 96

Port-site metastasis has been an unexpected finding after laparoscopic surgery in gastrointestinal cancer patients. No clear explanation exists for this phenomenom. The aims of this study were to evaluate the dissemination pattern in an experimental model of hepatocarcinoma in the rat and summarize current knowledge about the risks and the results of experimental studies on cancer dissemination during laparoscopic surgery. NDA-induced hepatocarcinoma was obtained in Sprague-Dawley rats. Tumors were manipulated during laparoscopy (group 1, n = 11) or laparotomy (group 2, n = 12). A Medline review of all experimental studies about the risk of cancer dissemination during laparoscopic surgery was undertaken. Both models were associated with implants in parietal wounds [1/11 in group 1 (9%) vs. 1/12 in group 2 (8%), p = NS]. Analysis of the current literature confirms that laparoscopy is associated with abdominal cell mobilization, and cells can be recovered in trocars, filtered exhaust gas, and instruments. Postoperative immunosuppression, the biologic aggressiveness of the tumor, and the gas used for laparoscopy also influence tumoral growth. Port-site metastases are secondary to multiple factors, including the technical skill of the surgeon, the biologic properties of the tumors, and local environmental aspects. Undoubtedly, laparoscopy can help disseminate aggressive tumors and should be reserved for diagnostic and staging procedures or for treatment of low-grade malignant tumors. Therapeutic resection, especially of colon cancer, should be restricted to prospective and randomized trials until there are enough hard data to rule out the clinical importance of this potentially severe complication.
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PMID:Cancer dissemination during laparoscopic surgery: tubes, gas, and cells. 1107 77

Despite several years of experimental observations, the clinical application of the neuroimmunomodulation is still at the beginning. The pineal gland plays a main role in mediating the link between psychoneuroendocrine and immune systems. Melatonin (MLT), which is the main pineal hormone produced during the night, has appeared to amplify IL-2 anticancer activity. Other pineal hormones, however, would have immunomodulatory activity, in particular 5-methoxytryptophol (5-MTT), which is mainly produced during the light phase of the day. Previous clinical studies have shown that low-dose IL-2 plus MLT may have therapeutic efficacy in advanced cancer patients with neoplasms generally resistant to IL-2 alone, with a tumor regression rate generally less than 20% and an acceptable toxicity. The present study was carried out to evaluate the efficacy of low-dose IL-2 in association with both MLT and 5-MTT. The study included 14 untreatable advanced solid tumor patients (lung cancer: 4; gastric cancer: 3; mesothelioma: 2; hepatocarcinoma: 2; pancreatic cancer: 1; melanoma: 1; colon cancer: 1). IL-2 was injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, by repeating a second cycle after a 21- day rest period. Both MLT and 5-MTT were given orally at 40 mg/day in the evening and at 1 mg/day at noon. The clinical results, as evaluated by WHO criteria after each cycle, consisted of partial response (PR) in 4/14 (29%) (lung cancer: 2; hepatocarcinoma: 1; mesothelioma: 1), stable disease (SD) in 6 and progressive disease in the last 4 patients. The treatment was extremely well tolerated in all patients, and in particular no fever greater than 38 degrees C occurred. These preliminary results show that the neuroimmunotherapy with low-dose IL-2 plus two pineal hormones, MLT and 5-MTT, is a well tolerated and potentially effective cancer therapy of untreatable advanced solid tumor patients, with results apparently superior with respect to those previously described with IL-2 plus MLT alone.
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PMID:Anticancer neuroimmunomodulation by pineal hormones other than melatonin: preliminary phase II study of the pineal indole 5-methoxytryptophol in association with low-dose IL-2 and melatonin. 949 62

Chemotherapeutic drugs cause DNA damage and kill cancer cells mainly by apoptosis. p53 mediates apoptosis after DNA damage. To explore the pathway of p53-dependent cell death, we investigated if p53-dependent apoptosis after DNA damage is mediated by the CD95 (APO-1/Fas) receptor/ligand system. We investigated hepatoma, gastric cancer, colon cancer, and breast cancer cell lines upon treatment with different anticancer agents known to act via p53 accumulation. Cisplatin, mitomycin, methotrexate, mitoxantrone, doxorubicin, and bleomycin at concentrations present in the sera of patients during therapy led to an upregulation of both CD95 receptor and CD95 ligand. Induction of the CD95 ligand occurred in p53 wild-type (wt), p53 mutant (mt), and p53 deficient (p53(-/-)) cell lines and at wt and mt conformation of temperature-sensitive p53 mutants. In contrast, upregulation of the CD95 receptor was observed only in cells with wt p53, not in cells with mt or without any p53. Restitution of inducible wt p53 function restored the ability of p53(-/-) Hep3B cells to upregulate the CD95 receptor in response to anticancer drugs. This rendered the cells sensitive to CD95-mediated apoptosis. In an attempt to understand how CD95 expression is regulated by p53, we identified a p53-responsive element within the first intron of the CD95 gene, as well as three putative elements within the promoter. The intronic element conferred transcriptional activation by p53 and cooperated with p53-responsive elements in the promoter of the CD95 gene. wt p53 bound to and transactivated the CD95 gene, whereas mt p53 failed to induce apoptosis via activation of the CD95 gene. These observations provide a mechanistic explanation for the ability of p53 to contribute to tumor progression and to resistance of cancer cells to chemotherapy.
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PMID:p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. 984 17

Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel oral fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FU) selectively in tumours through a cascade of three enzymes. The present study investigated tissue localisation of the three enzymes in humans, which was helpful for us to design the compound. Carboxylesterase was almost exclusively located in the liver and hepatoma, but not in other tumours and normal tissue adjacent to the tumours. Cytidine (Cyd) deaminase was located in high concentrations in the liver and various types of solid tumours. Finally, thymidine phosphorylase (dThdPase) was also more concentrated in various types of tumour tissues than in normal tissues. These unique tissue localisation patterns enabled us to design capecitabine. Oral capecitabine would pass intact through the intestinal tract, but would be converted first by carboxylesterase to 5'-deoxy-5-fluorocytidine (5'-dFCyd) in the liver, then by Cyd deaminase to 5'-deoxy-5-fluorouridine (5'-dFUrd) in the liver and tumour tissues and finally by dThdPase to 5-FU in tumours. In cultures of human cancer cell lines, the highest level of cytotoxicity was shown by 5-FU itself, followed by 5'-dFUrd. Capecitabine and 5'-dFCyd had weak cytotoxic activity only at high concentrations. The cytotoxicity of the intermediate metabolites 5'-dFCyd and 5'-dFCyd was suppressed by inhibitors of Cyd deaminase and dThdPase, respectively, indicating that these metabolites become effective only after their conversion to 5-FU. Capecitabine, which is finally converted to 5-FU by dThdPase in tumours, should be much safer and more effective than 5-FU, and this was indeed the case in the HCT116 human colon cancer and the MX-1 breast cancer xenograft models.
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PMID:Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. 984 91

A thymidylate synthase (TS)-ribonucleoprotein (RNP) complex composed of TS protein and the mRNA of the tumor suppressor gene p53 was isolated from cultured human colon cancer cells. RNA gel shift assays confirmed a specific interaction between TS protein and the protein-coding region of p53 mRNA, and in vitro translation studies demonstrated that this interaction resulted in the specific repression of p53 mRNA translation. To demonstrate the potential biological role of the TS protein-p53 mRNA interaction, Western immunoblot analysis revealed nearly undetectable levels of p53 protein in TS-overexpressing human colon cancer H630-R10 and rat hepatoma H35(F/F) cell lines compared to the levels in their respective parent H630 and H35 cell lines. Polysome analysis revealed that the p53 mRNA was associated with higher-molecular-weight polysomes in H35 cells compared to H35(F/F) cells. While the level of p53 mRNA expression was identical in parent and TS-overexpressing cell lines, the level of p53 RNA bound to TS in the form of RNP complexes was significantly higher in TS-overexpressing cells. The effect of TS on p53 expression was also investigated with human colon cancer RKO cells by use of a tetracycline-inducible system. Treatment of RKO cells with a tetracycline derivative, doxycycline, resulted in 15-fold-induced expression of TS protein and nearly complete suppression of p53 protein expression. However, p53 mRNA levels were identical in transfected RKO cells in the absence and presence of doxycycline. Taken together, these findings suggest that TS regulates the expression of p53 at the translational level. This study identifies a novel pathway for regulating p53 gene expression and expands current understanding of the potential role of TS as a regulator of cellular gene expression.
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PMID:Thymidylate synthase protein and p53 mRNA form an in vivo ribonucleoprotein complex. 989 Oct 91

To determine the role of the Wilms' tumor gene WT1 in tumorigenesis of solid tumors, expression of the WT1 gene was examined in 34 solid tumor cell lines (four gastric cancer cell lines, five colon cancer cell lines, 15 lung cancer cell lines, four breast cancer cell lines, one germ cell tumor cell line, two ovarian cancer cell lines, one uterine cancer cell line, one thyroid cancer cell line, and one hepatocellular carcinoma cell line) by means of quantitative reverse transcriptase-polymerase chain reaction. WT1 gene expression was detected in three of the four gastric cancer cell lines, all of the five colon cancer cell lines, 12 of the 15 lung cancer cell lines, two of the four breast cancer cell lines, the germ cell tumor cell line, the two ovarian cancer cell lines, the uterine cancer cell line, the thyroid cancer cell line, and the hepatocellular carcinoma cell line. Therefore, of the 34 solid tumor cell lines examined, 28 (82%) expressed WT1. Three cell lines expressing WT1 (gastric cancer cell line AZ-521, lung cancer cell line OS3, and ovarian cancer cell line TYK-nu) were further analyzed for mutations and/or deletions in the WT1 gene by means of single-strand conformation polymorphism analysis. However, no mutations or deletions were detected in the region of the WT1 gene ranging from the 3' end of exon 1 to exon 10 (the WT1 gene consists of 10 exons) in these three cell lines. Furthermore, when AZ-521, OS3, and TYK-nu cells were treated with WT1 antisense oligomers, the growth of these cells was significantly inhibited in association with a reduction in WT1 protein levels. Furthermore, constitute expression of the transfected WT1 gene in cancer cells inhibited the antisense effect of WT1 antisense oligomer on cell growth. These results indicated that the WT1 gene plays an essential role in the growth of solid tumors and performs an oncogenic rather than a tumor-suppressor gene function.
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PMID:Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. 1018 90

We have established monoclonal antibodies from mice immunized with the human hepatocellular carcinoma cell line, hu-H2. One of the antibodies, designated 523(KY-3), was reactive with this hepatocellular carcinoma cell line as well as with the human pancreatic cancer cell line, MIA. Another monoclonal antibody, 512(KY-2), only reacted with the hepato-cellular carcinoma cell lines. Neither antibody reacted with the colon cancer cell line CW3. Pretreatment of peripheral blood mononuclear cells with 523 resulted in enhancement of their natural cytotoxicity to hu-H2 (9.0 vs 18.4% in subject 1, 3.5 vs 14.7% in subject 2, and 14.2 vs 31.0% in subject 3). In contrast, such antibody mediated enhanced natural cytotoxicity was not found by pretreatment of the same peripheral blood mononuclear cell with 512. With the similarity in reactivity of 523, this antibody dependent enhancement was found in natural cytotoxicity to hu-H2 and MIA but not to CW3. Based on the facts that 523 did not have a direct cytopathic effect on these tumours and that this 523-mediated enhanced natural cytotoxicity was inhibited by anti-FcgammaRIII antibody, we concluded that the 523-mediated enhanced cytotoxicity reflects its activity to induce antibody dependent cytotoxic cells. Thus, these results demonstrate that several distinct tumour-specific antigens exist in hepatocellular carcinoma (HCC) and that one of them represents a potentially useful target for immunotherapy of human hepatocellular carcinoma.
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PMID:Antibody dependent cell-mediated cytotoxicity using hepatocellular carcinoma reactive monoclonal antibody. 1022 14

Proteases belonging to the caspase family play a crucial role in apoptotic processes. Identification of protein cleavage specific to apoptosis may therefore provide further information about the mechanisms of apoptosis. In this study, apoptosis and necrosis were induced in cells of the human colon cancer cell lines, WiDr and DLD-1, and the resulting protein cleavage patterns investigated for beta-catenin. beta-Catenin was detected as a 92 kDa protein in control viable cells, while 65-72 kDa beta-catenin cleavage fragments were characteristically observed in apoptotic cells. These fragments were not observed in necrotic cell death. Similar apoptosis-specific beta-catenin cleavage was also demonstrated in the rat hepatoma cell line McA-RH7777, suggesting that the beta-catenin cleavage is a common event in apoptosis in various cell types. The formation of 65-72 kDa beta-catenin cleavage fragments was completely prevented by a caspase-1 inhibitor Z-VAD-CH2F and a caspase-3 inhibitor Z-DEVD-CH2F, indicating that the cleavage is associated with caspase-dependent process. Since beta-catenin is implicated in cell adhesion and signal transduction, these findings may suggest various possible roles of beta-catenin degradation in the dramatic cytoskeletal and morphological changes, as well as signaling events that accompany apoptosis.
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PMID:Apoptosis-associated cleavage of beta-catenin in human colon cancer and rat hepatoma cells. 1022 75


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