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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlordecone (Kepone) has been extensively studied for its toxicity in male production workers who were exposed to large quantities of this organochlorine pesticide. Concern that these workers might be at an increased risk of developing liver cancer prompted us to test chlordecone in a two-stage rat model of hepatocarcinogenesis. Chlordecone acted largely as a liver tumor promoter rather than as a complete hepatic carcinogen in both male and female Sprague-Dawley rats. Dose-response experiments showed that the hepatocarcinogenic effects of long-term chlordecone administration became undetectable at concentrations in non-initiated rat liver in the same range as those measured in human biopsies taken from exposed workers who exhibited no liver effects. Although the toxicity of chlordecone in women has never been studied, we found a dramatic sex difference in the incidence of malignant liver tumors caused by chlordecone promotion in rats. Frank hepatocellular carcinomas were observed in up to 63% of female rats whose livers were previously 'initiated' with a subcarcinogenic dose of diethylnitrosamine given 24 h after partial hepatectomy, and then 'promoted' by 27 weeks of chlordecone administration. In contrast, none of comparably treated males had malignant liver tumors, even after 44 weeks of 'promotion' with chlordecone. Females in the diethylnitrosamine-initiated/chlordecone-promotion groups also contained gamma-glutamyltranspeptidase-positive 'preneoplastic' hepatocellular foci that were more abundant and larger than those observed in comparably-treated males. Moreover, because similar levels of chlordecone were measured in the livers of both sexes at the end of the experimental period, the development of hepatocellular carcinomas in the diethylnitrosamine-initiated female rats appeared to be due to their increased sensitivity to the promotion treatment.
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PMID:Evaluation of chlordecone in a two-stage model of hepatocarcinogenesis: a significant sex difference in the hepatocellular carcinoma incidence. 247 May 27

In 98 patients affected by colorectal cancer (43 patients with colon cancer, 55 patients with rectosigmoid cancer) the specificity of some tumor markers (CEA, GICA, TPA, alpha-FP, FpA, gamma-GT) has been tested in evidencing the coexistence of liver metastases and the site of the primary tumor, i.e. the rectosigmoid region (rectum + 15 cm of the adjacent sigmoid colon) vs the rest of the colon. Liver metastases, present in 19 patients with colon cancer and in 24 with recto-sigmoid cancer, were previously ascertained by various instrumental investigations. Unlike previous studies which indicated CEA or alpha-FP as the most reliable markers to suggest the coexistence of liver metastases in such patients, the reported results allow the following sequence, in decreasing order of sensitivity, to be proposed: gamma-GT; FpA; CEA and GICA to a similar degree; TPA, which increases only when liver metastases from colon cancer are present; lastly, alpha-FP, which rises only in very few cases of massive hepatic involvement.
Med Oncol Tumor Pharmacother 1989
PMID:Specificity of tumor markers (CEA, GICA, TPA, alpha-FP, FpA, gamma-GT) for the diagnosis of hepatic metastases from large bowel cancers. 247 62

Murine papilloma cell lines 308 and SP-1 have been used as recipients for transfected oncogenes to investigate malignant conversion. These cell lines express an activated c-rasHa gene with a codon 61 mutation and produce squamous papillomas when transplanted as skin grafts onto nude mice. They are not tumorigenic by subcutaneous injection. Both papilloma cell lines were stably transfected with plasmid DNA containing either a rearranged murine plasmacytoma-derived c-myc (minus exon 1), adenovirus 5 E1A, FBJ v-fos or a human c-fos/FBJ v-fos chimera, using cotransfection with the neomycin resistance gene contained in pSV2neo to select for transformants. Southern and northern blotting analysis confirmed the uptake and expression of exogenous DNA in both G418-selected cell lines and in the derived tumors. Unlike the E1A- and myc-containing plasmids, both fos constructs caused malignant conversion in either cell line, as defined by the squamous cell carcinoma histology of tumors from grafted cells and the development of carcinomas after subcutaneous injection into athymic nude mice. Immunofluorescence analysis for specific keratin gene expression indicated that tumors derived by introduction of either of the fos oncogenes were devoid of staining for K1, a 67 kDa epidermal keratin that is expressed in papillomas but not in squamous carcinomas. Tumors from E1A, myc, or pSV2neo transfectants expressed K1, although in a focal distribution. The malignant phenotype induced by the fos oncogene constructs was not associated with the ability to form agar colonies in vitro or to express gamma-glutamyl transpeptidase in the tumors. Since both 308 and SP-1 were sensitive to the fos oncogene for malignant conversion and insensitive to E1A or myc, it is possible that fos may cooperate with the endogenous-activated c-rasHa gene to convert these cells to malignancy. However, since gamma-glutamyl transpeptidase activity is found in the majority of chemically induced mouse skin carcinomas that possess an activated c-rasHa gene, fos activation may not be a common pathway for spontaneous malignant conversion.
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PMID:Malignant conversion of murine squamous papilloma cell lines by transfection with the fos oncogene. 247 37

A rat liver gap junction (GJ) cDNA probe that detects mRNA encoding the 32 Kd GJ-protein (connexin 32) was employed to study GJ-protein gene expression in rat liver tumors induced by a single exposure to diethylnitrosamine (DEN) followed by exposure to 2-acetylaminofluorene (AAF)/CCl4/AAF or induced by systemic administration of N-ethyl-N-hydroxyethylnitrosamine (EHEN). All carcinomas generated by these carcinogens showed markedly reduced levels of GJ-protein mRNA. This may indicate that GJ-protein levels and gap-junctional intercellular communication (GJIC) capacity are also severely compromised. Moreover, all hyperplastic nodules also showed a reduced level of GJ-protein mRNA. Taken together with our earlier finding that the liver tumor promoter phenobarbital inhibits GJ-protein gene expression, these results suggest that deranged GJIC is a relatively early event in liver multistage carcinogenesis. A range of other cDNA probes was also used to characterize gene expression in the DEN-induced tumors. Induction of expression was seen for glutathione S-transferase (placental form) (GST-P), gamma-glutamyltranspeptidase (GGT), and c-raf but not for c-Ha-ras or c-myc.
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PMID:Changes in gap junction protein (connexin 32) gene expression during rat liver carcinogenesis. 255 87

The reversible stage of tumor promotion, which follows the stage of initiation and precedes that of progression in multistage carcinogenesis, is a unique example of reversible toxicity in biological systems. In order to study the molecular mechanisms involved in the action of promoting agents during this stage, the regulation of the expression of genes for two enzymes of glutathione metabolism, gamma-glutamyl transpeptidase (GGT) and the placental isozyme of glutathione S-transferase (GST-P), was studied under several different conditions of promotion during multistage hepatocarcinogenesis in the rat. Promotion by phenobarbital caused an increased expression of both of these genes in altered hepatic focal lesions, although this was somewhat more variable in the case of the GGT gene. C.I. Solvent Yellow 14, an industrial dye, served as an effective promoting agent. Feeding this dye resulted in a dramatic increase in the expression of GST-P, but not that of GGT in altered hepatic foci. Factors in crude, cereal-based diets inhibited the stage of promotion by diethylnitrosamine, but enhanced promotion by phenobarbital in a synergistic manner. In contrast, at least one purified diet had the converse effect during this stage. The mRNA levels of GST-P were uniformly elevated dramatically in reversible nodules and neoplasms of rat liver that had been induced by diethylnitrosamine and phenobarbital promotion. In contrast, the level of GGT mRNA was somewhat variable, with an occasional neoplasm exhibiting almost a background level of expression of this gene. Therefore, the altered regulation of multiple genes in hepatocytes during the stage of promotion can vary with the promoting agent itself; this process may be related to the heterogeneous gene expression seen in hepatic neoplasms. A possible role for specific DNA sequences in the 5' flanking regions of such genes is considered. In addition, a cDNA clone to the mRNA of human liver GGT was isolated and sequenced. The homology of the coding sequence of the human liver GGT mRNA to that of rat kidney GGT mRNA was striking.
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PMID:Regulation of the expression of some genes for enzymes of glutathione metabolism in hepatotoxicity and hepatocarcinogenesis. 256 99

A fluorescent method developed for visualizing gamma-glutamyltranspeptidase (GGT) in intact liver cells was adapted to leukocytes and used in a multiparameter flow cytometric study of blood and bone marrow cells from rats with subcutaneous implants of mammary carcinoma 5A. The severe granulocytosis caused by this non-metastatic tumor was preceded by a progressive rise in the percentage of leukocytes with high GGT fluorescence. Both granulocytes and small, immature cells of bone marrow showed increased GGT expression, whereas in blood this increase was attributable entirely to mature granulocytes. At 28 days (but not yet at 14 days) after carcinoma implantation, 20-30% of blood or bone marrow granulocytes constituted a distinct subpopulation in that their GGT fluorescence intensity range was much higher and did not overlap with the range for the rest of the population. The results indicate that fluorescent GGT assay of intact leukocytes provides a useful probe for flow cytometric analysis of population heterogeneity in leukoproliferative disorders.
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PMID:gamma-Glutamyltranspeptidase activity in intact leukocytes: flow cytometric analysis and sorting. 256 47

Three clones of the pig kidney cell line LLC-PK1 were isolated and characterized with regard to morphology, growth, proximal tubule enzyme activity, sugar uptake capacity, and hormone and drug responsiveness in a defined medium. Clone N4 was similar in morphology to the wild type (WT), whereas clone F8 showed loose attachment to the substrate, formed large, sweeping domes, and had an elongated desmosome junction between cells. The third clone, F2, did not form domes and showed a marked reduction in growth rate. Cultures of WT, N4, and F8 had higher specific activities of the enzyme alkaline phosphatase and gamma-glutamyl transpeptidase at confluence relative to growing cells; however, there was no evidence of an increase in activity of either enzyme at confluence in F2. Phlorizin-sensitive alpha-methyl-D-glucoside uptake and cytochalasin B-sensitive 2-deoxy-D-glucose uptake were measured in confluent cultures grown on porous filter supports. None of the clones lacked either of the hexose transport systems, although quantitative differences were evident. N4 cells grown in a defined medium in 96-well culture plates were tested in situ for their enzyme responses to differentiation inducers, tumor promoters, and hormones. Alkaline phosphatase activity was significantly increased at confluence by serum, parathyroid hormone (PTH), and vasopressin (AVP), and was decreased by tetradecanoylphorbol acetate (TPA) and epinephrine (EPI). Glutamyl transpeptidase activity was decreased at confluence by serum, TPA, and EPI. Similar tests on alpha-methyl-D-glucoside uptake showed that serum, TPA, PTH, and AVP had no significant effect on phlorizin-sensitive uptake; however, calcitonin increased uptake by 84% (n = 18). It was concluded that LLC-PK1 clones maintained in a defined medium are useful models for studying renal cell function.
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PMID:Growth, enzyme activity, sugar transport, and hormone supplement responses in cells cloned from a pig kidney cell line LLC-PK1. 256 38

The effect of feeding a choline deficient (CD) diet, an efficient liver tumor promoting regimen, on the prostaglandin metabolism in the liver of male Sprague-Dawley rats was investigated. The possible biological significance of the alteration was examined using hypolipidemic peroxisome proliferators and modifiers of prostaglandin metabolism such as indomethacin and menhaden oil in the short term assay of the induction of enzyme altered foci in the liver. A CD diet, when fed for 10-30 days, induced 2-2.5 times increases in the levels of prostaglandin E2 (PGE2) in the liver, while the hypolipidemic peroxisome proliferators, 4-chloro-6(2,3-xylidino) pyrimidinylthio(N-hydroxyethyl)-acetamide (BR931) and di(2-ethylhexyl)-phthalate (DEHP), markedly reduced the levels of this metabolite. The addition of BR931 or indomethacin to a CD diet suppressed the diet-induced elevations of PGE2 and a substitution of fats in a CD diet with menhaden oil had the same effect. Furthermore, both indomethacin and menhaden oil added to a CD diet suppressed the induction of gamma-glutamyltranspeptidase positive hepatocyte foci in the liver of rats initiated with a single dose of diethylnitrosamine after 8 weeks of the dietary promotion. The results suggest that altered prostaglandin metabolism may be involved in the liver tumor promoting effect of a CD diet.
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PMID:Elevated levels of prostaglandin E2 in the liver of rats fed a choline deficient diet: possible involvement in liver tumor promotion. 256 85

Immunoreactive gamma-glutamyl transpeptidase in human serum and liver tissue was measured by a solid phase enzyme-linked immunosorbent assay. The immunoreactive gamma-glutamyl transpeptidase was significantly elevated in the sera of patient with hepatocellular carcinoma. On the other hand, in sera of patients with non-neoplastic diseases, including chronic hepatitis, acute hepatitis, fatty liver and hemangioma, the immunoreactive gamma-glutamyl transpeptidase was not elevated. In hepatocellular carcinoma and metastatic liver tumor tissues, the immunoreactive gamma-glutamyl transpeptidase content was also elevated, showing good correlation with the enzyme protein content in sera. However, no correlation was found between the activity of gamma-glutamyl transpeptidase determined by an enzymatic assay and the content determined by an enzyme-linked immunosorbent assay. On immunohistochemical examination, the immunoreactive enzyme protein without enzymatic activity was detected only in the cytoplasm of cancer cells. This suggested that there is an increased level of the immunologically active but enzymatically inactive form of gamma-glutamyl transpeptidase in hepatoma tissues.
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PMID:Measurement of immunoreactive gamma-glutamyl transpeptidase in human sera and liver tissues of patients with various liver diseases. 257 Jul 27

Contents of 22 amino acids in hepatoma with surrounding and distant liver parenchyma resected from 10 pathologically proven patients were determined using high performance liquid chromatography. Analysis of the results showed that the contents of total amino acids and essential amino acids in hepatoma tissues were much higher than those in the surrounding and distant liver parenchyma. The contents of 11 amino acids, including glutamic acid, asparagine, glutamine, serine, histidine, arginine, tryptophan, methionine, leucine, isoleucine and lysine were higher than those in the surrounding and/or distant liver parenchyma. There was no statistically significant difference of amino acid contents between the surrounding and distant liver parenchyma. Most amino acid contents which increased in hepatoma tissues were positively correlated with tumor volume and/or serum gamma-glutamyl transpeptidase activity. These results suggested that hepatoma tissues can selectively take up the necessary amino acids which fail to be produced by the cancer tissues as raw material for synthesis of protein. The faster the hepatoma grows, the greater the need for amino acidosis. This study may be helpful to the application of imbalanced amino acid for correction of metabolic disturbances in hepatoma patients.
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PMID:[Changes in amino acid contents in hepatocellular carcinoma tissues]. 257 11


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