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

In previous studies, we have found that combined treatment with BCNU and sodium cyanate could have a greater effect on the survival of mice bearing B16 melanoma than treatment with either agent alone. With rat hepatoma and human colon cancer cells in culture, we have obtained evidence that the inhibition of cell proliferation by sodium cyanate is greater at pH 6.6 than at pH 7.4. In the present work, the effects of combination treatments on the proliferation of cancer cells were studied with cyanate, pH, BCNU, and hyperthermia. With HT29 human colon cancer cells, the inhibitory effect of BCNU (50-100 micrograms/ml) was greater when the cells were treated at pH 6.6 than at pH 7.4. The influence of pH appeared to be absent or minimal at lower or higher concentrations of BCNU. We confirmed our previous observation that the inhibition of proliferation of LS174T human colon cancer cells is greater at pH 6.6 than at pH 7.4, and we observed an inhibitory effect of BCNU (50 or 200 micrograms/ml). However, no more than additive effects were seen with combination treatment. An inhibitory effect of hyperthermia was seen for the incorporation of [3H]-leucine into protein of rat hepatoma cells (HTC) and for that of [3H]-thymidine into DNA of human colon cancer (HT29) cells. In neither case was the effect of hyperthermia significantly enhanced by treatment with sodium cyanate beyond that seen with one of the treatments alone. The data confirmed that the inhibitory effect of sodium cyanate on cell proliferation can be enhanced by a low pH but did not provide evidence for synergistic effects in combination with BCNU or hyperthermia.
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PMID:Combined effect of pH and sodium cyanate on the inhibition of tumor cell proliferation and metabolism by BCNU and hyperthermia. 236 91

Six cell lines differing in histological origin were studied regarding the growth inhibitory effect of fluoropyrimidines in relation to their metabolism. The human colon carcinoma cell line WiDr was most sensitive to 5-fluorouracil (FUra) (50% growth inhibitory concentration, 0.7 microM) and to its analogue 5'deoxy-5-fluorouridine (5'dFUR) (50% growth inhibitory concentration, 18 microM). The murine B16 melanoma cell line was moderately sensitive to FUra but least sensitive to 5'dFUR. The 50% growth inhibitory concentration values in the human melanoma cell lines IGR3 and M5, the transformed human intestine cell line intestine 407 and the rat hepatoma cell line H35 varied for FUra between 1.7 and 5.0 microM, and for 5'dFUR between 54 and 160 microM. Several enzymes from pyrimidine metabolism responsible for FUra metabolism were measured with FUra as a substrate. The activity of uridine phosphorylase, which catalyzes the conversion of 5'dFUR to FUra, was lowest in B16 cells correlating with the low sensitivity to 5'dFUR. When adenosine 5'-triphosphate was included in the reaction mixture for uridine phosphorylase, FUra was rapidly channeled into FUra nucleotides via its nucleoside. The rate of channeling appeared to correlate with the nucleoside phosphorylase activity in the various cell lines. In several cell lines activities of nucleotide-degrading enzymes were rather high and interfered with the measurement of orotate phosphoribosyl transferase (OPRT) with FUra as substrate. Addition of the phosphatase inhibitor glycerol-2-phosphate partly prevented breakdown of the newly formed 5-fluorouridine 5'-monophosphate and enabled measurement of OPRT. The WiDr cell line had a relatively high OPRT activity which could explain its sensitivity to FUra. The activity of thymidylate synthase was measured at a suboptimal concentration of 1 microM and at the optimal concentration of 10 microM deoxyuridine 5'-phosphate. With all cell lines the ratio between the activities at 10 and 1 microM was between 2.3 and 3.6. The activity of thymidylate synthase was lowest in WiDr and IGR3 cells and 3-4 times higher in M5 and Intestine 407 cells. The inhibition of 0.01 microM 5-fluorodeoxyuridine 5'-monophosphate was 80-90% at 1 microM deoxyuridine 5'-phosphate and 50-70% at 10 microM deoxyuridine 5'-phosphate with all cell lines. At 0.1 microM 5-fluorodeoxyuridine 5'-monophosphate enzyme activity was inhibited by 95-100%. The incorporation of FUra into RNA was relatively low in IGR3 cells and 3-5 times higher in all other cell lines.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sensitivity of human, murine, and rat cells to 5-fluorouracil and 5'-deoxy-5-fluorouridine in relation to drug-metabolizing enzymes. 241 45

A murine monoclonal antibody that reacts with human colonic cancer (250-30.6) was labeled with radioactive iodine (131I) and the antibody was injected intravenously into 15 patients with known metastases originating from carcinoma of the colon (10 cases), malignant melanoma (1), breast (1), pancreas (1), hepatocellular carcinoma (1), and adenocarcinoma of unknown origin (1). Of the patients with metastatic colon carcinoma, there were 19 known deposits as judged by the techniques of clinical examination, x-rays, and scans obtained using sulpha-colloid. Of these 19 deposits, 17 (90%) were found using the 131I-labeled monoclonal antibody. In one case, the primary tumor, previously undiagnosed, was found. In only 1 of the 10 patients was tumor not found and this was due to the subsequent finding that the undifferentiated tumor did not react with antibody. Of the five patients who did not have carcinoma of the colon, three had negative scans, but two were positive. Thus, the technique of immunoscintography can readily detect both primary and metastatic tumors.
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PMID:Visualization of metastases from colon carcinoma using an iodine 131-radiolabeled monoclonal antibody. 241 93

Metastatic poorly differentiated carcinomas often represent diagnostic difficulties in surgical pathology. Therefore, the expression of cytokeratins of different molecular weights (54, 57, and 66 kd) were compared in paraffin sections of 37 primary carcinomas with their lymph node metastases by an avidin-biotin complex (ABC) method, using monoclonal antibodies. The epithelial tumors consisted of 16 squamous cell carcinomas (SCCs) and 17 adenocarcinomas with different degrees of differentiation (well, moderately, or poorly differentiated), a renal cell carcinoma, a hepatocellular carcinoma, a transitional cell carcinoma of the bladder, and a carcinoid tumor of the stomach. The primary and metastatic tumors showed the same cytokeratin profiles. All SCCs and their metastases were positive for 57-kd cytokeratin and negative for 54-kd cytokeratin. All adenocarcinomas and their metastases were positive for 54-kd cytokeratin and negative for 66-kd cytokeratin. The extent of reactions varied with the differentiation of the carcinomas, with well-differentiated tumors showing more diffuse staining. Cases of lymphoma, sarcoma, and melanoma were negative for the three types of cytokeratins. The results indicate that identification of different molecular weight cytokeratins may be used to distinguish poorly differentiated SCCs from poorly differentiated adenocarcinomas, even in metastatic tumors. In addition, demonstration of these cytokeratins is useful in substantiating presence and identity of small foci of metastases in lymph nodes.
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PMID:Comparison of cytokeratin expression in primary and metastatic carcinomas. Diagnostic application in surgical pathology. 243 26

The use of immunoperoxidase techniques was investigated in 21 fine needle aspiration (FNA) cytology smears that had been previously stained by the Papanicolaou technique. The retrospectively selected slides were destained before applying the immunostain, utilizing antisera to calcitonin, prostatic acid phosphatase (PrAP), prostate-specific antigen (PSA), alpha-lactalbumin (AL), S-100 protein (S-100), carcinoembryonic antigen (CEA), common leukocyte antigen (LA), epithelial membrane antigen (EMA) and alpha-fetoprotein (AFP). Positive results were obtained with six of nine small-cell carcinomas of the lung stained with EMA, all three colonic carcinomas stained with CEA, one of two prostatic carcinomas stained with PSA and PrAP, one of two lymphomas stained with LA and the one medullary thyroid carcinoma stained with calcitonin. Negative staining results were observed in the one melanoma stained with S-100, the two breast carcinomas stained with AL and the one hepatocellular carcinoma stained with AFP. These results indicate that immunostaining can be a helpful diagnostic tool in diagnosing some fine needle aspirates using smears previously stained with the Papanicolaou stain.
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PMID:Immunoperoxidase staining of fine needle aspiration specimens previously stained by the Papanicolaou technique. 244 Feb 15

Unstimulated and interferon (IFN)-stimulated natural killer cell (NK) activity was investigated in patients with malignant melanoma prior to the removal of the primary melanoma (stage I disease) or in patients with melanoma metastases. Unstimulated as well as IFN-stimulated NK activities, directed against the primarily NK-sensitive K562 cell line, were found not to differ significantly from the NK activity of healthy control subjects. In contrast, IFN-stimulated NK activity directed against the primarily NK-insensitive Chang hepatoma and JY cell lines was significantly lower in patients with metastatic melanoma than in patients with non-metastatic disease (Chang hepatoma cell line: P less than 0.02; JY cell line: P less than 0.0017) and - in experiments using the JY cell line - than in healthy controls (P less than 0.01). Stage I melanoma patients did not differ in their IFN-induced NK activity from healthy control subjects using Chang hepatoma and JY cell lines. Finally, the IFN-induced increase in NK activity directed against primarily NK-insensitive target cell lines was significant in stage I melanoma patients and in healthy controls (P less than 0.01, respectively), but not in patients with metastatic melanoma (P greater than 0.5). We thus conclude that patients with metastatic malignant melanoma exhibited a defect in IFN-augmented NK activity directed against primarily NK-insensitive targets.
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PMID:Defective interferon-augmented natural killer cell activity in patients with metastatic malignant melanoma. 247 50

An experimental study using human melanoma (NEL-MI), rat hepatoma (Fu5-5), and human kidney (293-31) cell lines was undertaken in order to evaluate the antitumor activity of 4-hydroxyanisole (4-OHA) in vitro. Prior reports have indicated highly specific antitumor activity of 4-OHA against melanoma cells in vitro. This specific antitumor activity has been proposed to be due to the oxidation of 4-OHA by tyrosinase to cytotoxic oxidation products. Dose-dependent cytotoxicity was observed when cells were cultured for 72 h in the presence of 4-OHA. At 100 microM, 4-OHA produced growth inhibition of 62%, 32%, and 55% in melanoma, hepatoma, and kidney cell lines, respectively. No effect was seen at 10 microM 4-OHA. 1,000 microM 4-OHA produced 100% kill. Tyrosinase activity was detected only in melanoma cells. The effect of 100 microM 4-OHA on the incorporation of 3H DNA precursors in melanoma, hepatoma, and kidney cells was also studied. Thymidine incorporation was inhibited in all three cell lines at the lowest cell density tested, with the greatest inhibition seen on melanoma cells. As cell density increased, the effect of 4-OHA on thymidine incorporation decreased. With respect to RNA synthesis, 4-OHA significantly reduced the incorporation of uridine in all three cell lines, with the greatest effect in melanoma cells. Cell density also affected the inhibition of uridine incorporation, but to a lesser extent than that observed on thymidine incorporation. The effect of 4-OHA on leucine incorporation was modest and uninfluenced by cell density. Thus, cytotoxicity of 4-OHA may involve two different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specificity of growth inhibition of melanoma by 4-hydroxyanisole. 249 44

Hepatic metastases represent a common site of dissemination for a number of primary malignancies related in part to the dual blood supply, large blood flow, and receptive environment of the hepatic parenchyma. Although this review focuses on regional therapy, we have included sections on systemic therapy to better interpret the results with intrahepatic therapy. We will also discuss the efficiency of hepatic arterial ligation, embolization, and radiotherapy of hepatic metastases. Primary gastrointestinal neoplasms are particularly prone to produce hepatic metastases. Because colorectal carcinoma metastasizes to the liver in up to 70% of patients with advanced disease, the treatment of hepatic metastases is a relevant topic. We will discuss the systemic and regional therapy of colorectal, gastric, and gallbladder cancers. Breast carcinoma and malignant melanoma frequently metastasize to the liver, and we have described systemic and regional treatments of these diseases. Because sarcomas are often treated by regional therapy, we have included a section on the treatment of hepatic sarcomas. Neuroendocrine tumors (carcinoid and islet cell), although often slow growing, frequently metastasize to the liver and then cause symptomatic problems. Much of the work done with embolization and hepatic ligation in the treatment of hepatic metastases has been performed in neuroendocrine tumors, and these studies, as well as the systemic and regional chemotherapy of hepatic metastases, will be described. The last section concerns the treatment of hepatocellular carcinoma. We have outlined the staging systems used. We then detail the results of systemic and intrahepatic therapy, embolization, and hepatic ligation in the treatment of hepatocellular carcinoma. Because hepatic metastases are a frequent problem, many patients are available for clinical investigation. It is hoped that newer strategies for the treatment of liver metastases will lead to higher response rates and perhaps control of local disease. These therapeutic approaches may also give us leads to the treatment of systemic disease.
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PMID:Regional treatment of hepatic metastases and hepatocellular carcinoma. 254 12

A panel of seven murine monoclonal antibodies reactive with human hepatocellular carcinoma (HCC) cell line, SK- HEP-1, resulted in the definition of four distinct antigen systems, designated HB4, HB5, HB1 and HJ2. HB4 antigen was found to be expressed specifically on HCC cell lines and fresh HCC specimens but not on normal liver. Immunoprecipitation tests suggest that the HB4 epitope may be a heat-stable carbohydrate determinant on a high molecular mass molecule. HB5 antigen was found to have less-restricted expression on a panel of normal adult tissues and on melanoma, astrocytoma, sarcoma, neuroblastoma and epithelial cancer cell lines. In fetal and adult liver, HB5 antigen localized to bile canaliculi and ducts. Under reducing conditions, three mAbs detected a Mr 140,000 glycoprotein using lysates of [125-I], [3-H]-glucosamine and [35-S]-methionine labeled SK-HEP-1 cells. Under non-reducing conditions an additional component of greater than Mr 200,000 was also detected. HB1 antigen was found on almost all monolayer cell lines and not on most cultured suspension cells. This antigen was also detected on cultured HCC cells inoculated into nu/nu mice. Immunoprecipitation experiments revealed that the HB1 antigen is a bimolecular complex with an Mr 170,000 alpha chain and Mr 130,000 beta chain under non-reducing conditions, and three subunits of Mr 140,000, Mr 30,000 and Mr 130,000 under reducing conditions. Two antibodies reacted with epitopes on the alpha chain. HJ2 antigenic determinant is a heat-stable component which could not be immunoprecipitated. This most widely expressed antigen was found in secreted form in many of the cells and tissues examined. These antibodies introduce new antigens which may serve as useful markers for the diagnosis, classification and investigation of HCC and other liver diseases.
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PMID:Serological analysis and biochemical characterization of monoclonal antibodies defining antigens of human hepatocellular carcinoma. 255 3

Three inhibitors of S-adenosylmethionine-mediated transmethylation, 5'-methylthioadenosine (MTA), 2'-deoxyadenosine and sinefungin, inhibited in vitro invasion by a highly invasive clone (Cl-30) of rat ascites hepatoma cells, AH 130 (AH cells). Difluoromethylthioadenosine (DFMTA), a non-metabolizable derivative of MTA, also caused strong inhibition of invasion at concentrations that did not suppress the growth of the tumor cells. Cl-30 cells precultured in methionine-depleted medium showed decreased invasiveness. DFMTA was also effective on the invasion by fibrosarcoma, B16 melanoma and human lung carcinoma cell lines.
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PMID:Inhibition of in vitro tumor cell invasion by transmethylation inhibitors. 255 19


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