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

A report is given of the clinical and autopsy findings of two men who died from malignant liver neoplasm following occupational exposure to vinyl chloride. The first patient was a 44-year-old man with an hemangiosarcoma of the liver, the second patient a 67-year-old man with an hepatocellular carcinoma. So far an hepatocellular carcinoma due to vinyl chloride has not yet been observed in man. Its occurrence, however, has been suggested from the results of animal experiments. The connection of hepatocellular carcinoma with exposure to vinyl chloride is discussed.
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PMID:Hemangiosarcoma and hepatocellular carcinoma of the liver following vinyl chloride exposure. A report of two cases. 18 89

This report deals with a 51 years-old man who, for 23 years and 4 months of his working life, had been exposed to vinyl chloride vapors. Autopsy revealed a hepatoma associated with an angiosarcoma of the liver. The case is the first ever to be reported in the medical literature. This case raises doubts about the theory which suggests that the carcinogenic effect of vinyl chloride in man elicit a tumor of vascular nature.
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PMID:[Association of angiosarcoma of the liver and hepatoma in vinyl chloride worker]. 21 80

Trichloroethylene (TCE), a structural analog of vinyl chloride, is known to induce hepatocellular carcinoma and other tumors in C57BL/6 X C3H/He F1 (hereafter known as B6C3F1) hybrid mice. TCE epoxide, a possible metabolite, is expected to be highly reactive toward cellular nucleophiles, e.g., proteins and nucleic acids. Hence, the microsomal metabolism of TCE and its covalent binding to microsomal protein were examined. Rat liver microsomes were incubated in vitro with [14C]TCE. The results showed that TCE binds covalently to microsomal protein since extensive organic extractions and Pronase digestion do not dissociate the TCE-protein complex. The binding was decreased by 7,8-benzoflavone, blocked by SKF-525A, and enhanced by i.p. administration of phenobarbital. The possibility that TCE epoxide, once formed, could be converted to water-soluble products through enzymatic hydrolysis by epoxide hydrase was also investigated. Addition of 3,3,3-trichloropropene oxide, a potent inhibitor of epoxide hydrase, to the incubation system markedly enhanced the binding of TCE. These observations support the view that, in order to bind to protein, it is necessary for TCE to be metabolized to its epoxide, a reactive intermediate that is most likely involved in TCE carcinogenesis and toxicity.
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PMID:Covalent interaction of metabolites of the carcinogen trichloroethylene in rat hepatic microsomes. 127 48

An FMN-dependent NADH-quinone reductase is induced in Escherichia coli by growing the cells in the presence of menadione (2-methyl-1,4-naphthoquinone). Since the properties of induced enzyme are very similar to those of NAD(P)H: (quinone-acceptor) oxidoreductase (EC 1.6.99.2), known as DT-diaphorase, from animal cells, structural requirements of quinone derivatives as an inducer of NADH-quinone reductase in E. coli were examined. Among quinone derivatives examined, it was found that 2-alkyl-1,4-quinone structure with C-3 unsubstituted or substituted with Br is critical as a common inductive signal. Michael reaction acceptors which have been reported to be strong inducers of DT-diaphorase in mouse hepatoma cells were not always effective inducers in E. coli. However, several compounds, such as 2-methylene-4-butyrolactone, methylacrylate and methyl vinyl ketone, showed a slight inductive activity. The efficient inducers of NADH-quinone reductase in E. coli contain 1,4-quinone structure as a part of the inductive signal. These compounds belong to Michael acceptors and are likely to conjugate with thiol compounds such as glutathione.
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PMID:Chemical structures critical for the induction of FMN-dependent NADH-quinone reductase in Escherichia coli. 154 1

The possible association in humans between nonangiosarcoma primary liver tumors (PLC-non-A), particularly hepatocellular carcinoma (HCC), and exposure to vinyl chloride monomer (VCM) is supported by both experimental and human data. This article presents a review of the information regarding 253 deaths that occurred in seven plants manufacturing VCM/PVC and one plant extruding PVC. The retrieval of clinical and pathological data, in addition to the information from death certificate, is referred to as "best evidence" (BE). BE has been carried out for 63 deaths. A total of 14 primary liver cancer (PLC) were detected: seven were angiosarcoma (PLC-A), and two of the remaining seven were hepatocellular carcinoma (HCC). In our series of 14 PLC cases, there was no significant difference between PLC-A and PLC-non-A as to length of exposure and latency. There was no noticeable difference in terms of job title between ASL and non-ASL cases. The list of longest held jobs shows the presence of various job titles, different from autoclave cleaner, for primary liver cancer, PLC-A and PLC-non-A. In conclusion, our observations show that VCM may have a broader carcinogenicity action on the liver and that exposure lower than that occurring in autoclave cleaning can cause primary liver cancer, both angiosarcoma and nonangiosarcoma.
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PMID:Mortality from liver disease among Italian vinyl chloride monomer/polyvinyl chloride manufacturers. 215 96

With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogues of protoporphyrin, in which the vinyl group(s) were replaced by difluorovinyl group(s), were synthesized by the reaction of the formylporphyrins with sodium chlorodifluoroacetate in the presence of triphenylphosphine. Some improvements in the reported procedures for the synthesis of formylporphyrins are also described. Preliminary results of biological tests of the products showed that 8(2),8(2)-difluoroprotoporphyrin accumulates to gastric cancer more selectively than other fluorine analogues and that 3(2),3(2),8(2),8(2)-tetrafluoroprotoporphyrin is taken up by rat hepatoma cells more readily than the others.
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PMID:Synthesis of fluorine analogues of protoporphyrin potentially useful for diagnosis and therapy of tumors. 227 79

The antitumor and immunoadjuvant action of water-soluble N-vinylpyrrolidone co(ter)polymers of different chemical structure is studied. It is established that terpolymer N-vinyl-pyrrolidone (VP)--crotonic acid (CA)--n-crotonoylaminophenol inhibiting the growth of hepatoma 22a by 50-60% possesses an antitumoral action, while copolymer VP-CA has an immunoadjuvant action. These properties of co(ter)polymers are due to their chemical structure and molecular weight, but they do not always correlate between themselves.
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PMID:[Antineoplastic and immunostimulating effects of several N-vinylpyrrolidone co(ter)polymers in C3HA strain mice with hepatoma 22a]. 234 26

N6,N6-Dibenzoyl-2',3'-O-isopropylideneadenosine, which is readily synthesized by one-pot 5'-O-trimethylsilylation, N6-benzoylation, and desilylation, was converted to the corresponding 5'-aldehyde. This was treated with CH2 = CHMgBr to afford, after debenzoylation, a 1:3 mixture of the 5'S and 5'R epimers, respectively, of 5'-C-vinyl-2',3'-O-isopropylideneadenosine. The configurations were established by single-crystal X-ray diffraction analysis of the 5'R epimer. Hydroboration of the 5'-O-tetrahydropyranyl derivative of the mixed epimeric 5'-C-vinyl nucleosides readily furnished 5'(S,R)-C-(2-hydroxyethyl)-2',3'-O-isopropylideneadenosine. Treatment of the 5'(S,R)-C-(2-O-tosyl) derivative of this with disodium L-homocysteinate permitted facile introduction of the L-ethionine system. By means of methods developed earlier in the synthesis of homologous methionine-ATP adducts, the alpha-amino acid group was protected, a beta,gamma-imidotriphosphoryl group was introduced at O5', and blocking groups were removed to give the title adduct as a 2:3 mixture of its two 5' epimers. It was a powerful inhibitor [KM(ATP)/Ki = 520 and 340] of the M-2 (normal tissue) and M-T (hepatoma tissue) forms, respectively, of the title enzyme and displayed predominantly competitive kinetics with the two substrates L-methionine and MgATP. It inhibited M-2 and M-T slightly less effectively than its homologue possessing one less CH2 between sulfur and C5' and gave kinetic evidence of an increased tendency to form L-methionine-enzyme-adduct and MgATP-enzyme-adduct complexes.
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PMID:Approaches to isozyme-specific inhibitors. 16. A novel methyl-C5' covalent adduct of L-ethionine and beta,gamma-imido-ATP as a potent multisubstrate inhibitor of rat methionine adenosyltransferases. 278 35

On the occasion of a hitherto unique observation of three hepatocellular carcinomas in workers of the same industrial plant within 7 years following long-term exposure to vinylchloride, the characteristics are discussed of a chemical carcinogenesis leading to two different malignant tumours: haemangiosarcoma and hepatocellular carcinoma. This carcinogenic sequence has been predicted by animal studies. It is not known why the transformation of hepatocytes into carcinoma is far rarer than of sinusoidal cells into sarcoma. Whereas the hepatocellular carcinoma predominantly develops in association with cirrhosis, vinyl chloride is able to cause cancer directly without other known co-carcinogenic agents. This hepatic carcinogenicity is dose-dependent. After the introduction of industrial prevention measures, a new initiation of the tumour is improbable. Nevertheless, because of its long latency period, estimated between 5 and 20 years, clinical manifestations are still possible. An early diagnosis by sonography and computertomography, possibly combined with puncture, in exposed persons or those formerly at high risk is conceivable, while laboratory data, even tumour markers are unreliable. Its fulminant course does not differ from that of other hepatocellular carcinomas and has until now hindered successful treatment.
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PMID:[Vinyl chloride induced hepatocellular carcinoma]. 298 2

Hepatocarcinogenesis in rats treated with several chemicals is associated with changes in aldehyde dehydrogenase (AlDH) activity, particularly heterogeneous expression of a "tumor specific" phenotype that is very active with aromatic aldehydes, e.g., benzaldehyde (Bz). Objectives of this study were first, to determine if liver cancers in vinyl chloride-treated rats also expressed this AlDH phenotype, and second, to quantitate the NAD- and NADP-dependent AlDH activity for the substrates Bz and acetaldehyde (Ac) in the cancers and surrounding tissue. Small cubes of tissue containing well-differentiated hepatocellular carcinoma were obtained from five Sprague-Dawley rats exposed to 2500 ppm vinyl chloride for 55 weeks. An optimized procedure was developed for AlDH histochemistry. Frozen sections were preincubated in nitroblue tetrazolium/acetone and then incubated at 20 degrees C in viscous polyvinyl alcohol media containing buffer, phenazine methosulfate, sodium azide, substrate, coenzyme, and nitroblue tetrazolium. Background activity was evaluated by omission of substrate. Activity was quantitated by computer-assisted microscopic photometry. All five carcinomas had heterogeneous staining of NADP- and NAD-dependent BzDH and AcDH activity, with clusters of very high-activity cells. The magnitude of staining in the high-activity neoplastic cells was at least tenfold greater for BzDH-NADP and about twofold greater for BzDH-NAD, AcDH-NADP, and AcDH-NAD than the staining in other liver cells. More neoplastic cells had high BzDH than high AcDH activity. Only BzDH-NADP was localized predominantly to the carcinoma.
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PMID:Quantitative histochemistry of benzaldehyde dehydrogenase in hepatocellular carcinomas of vinyl chloride-treated rats. 300 81


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