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)

Examinations were made on substances that enhance or inhibit the induction of hepatoma in rats previously fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) for a brief period. The substances tested were stilbene, 4-nitrostilbene, 4,4'-dihydroxystilbene, diethylstilbestrol, 17beta-estradiol, and methyltestosterone. Male Donryu rats were fed 0.5 g of 3'-Me-DAB by being maintained on a diet containing 0.06% 3'-Me-DAB, and then they were fed 0.25 or 0.5 g of a test substance with the basal diet. Comparison of the development and yield of hepatomas indicated that 4-nitrostilbene and methyltestosterone had an activity of enhancing 3'-Me-DAB carcinogenesis, whereas diethylstilbestrol and 17beta-estradiol had an activity to retard it. Other substances showed no such activities. The enhancement by 4-nitrostilbene and inhibition by diethylstilbestrol of 3'-Me-DAB carcinogenesis was correlated with their effect on liver nucleic acid metabolism. Feeding of 4-nitrostilbene caused a selective inhibition of Mn2+-(NH4)2SO4-activated RNA polymerase activity of liver nuclei and reduced liver RNA content. The deleterious alteration of liver RNA metabolism was followed by the enhancement in the incorporation of ip-injected 3H-thymidine into DNA of liver nuclei. On the other hand, feeding of diethylstilbestrol increased tissue RNA content without effect on RNA polymerase activity of liver nuclei, and had an activity of increasing the incorporation of 3H-thymidine into DNA. The possible implication of these results with regard to the enhancement and inhibition of hepatocarcinogenesis is discussed.
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PMID:Enhancing and inhibitory effects of some stilbene and steroid compounds on induction of hepatoma in rats fed 3'-methyl-4-(dimethylamino)azobenzene. 20 6

In order to know the clinical significance of serum ribose-5-phosphate isomerase (RPI), the activity of this enzyme was determined in sera of normal subjects and patients with hepatic disorders or malignant tumors. Experimentally, the enzyme activity in sera and liver tissue was followed in rats with acute hepatic damage induced by carbon tetrachloride (CCl4) or rats with hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The following results were obtained: 1) Serum RPI activity increased markedly in rats with CCl4-induced liver damage, whereas the activity in liver tissue decreased, both being related with reciprocally. 2) In the early phase of acute hepatitis, serum RPI activity increased and gradually decreased thereafter. No significant increase was observed in other hepatic disorders. 3) Both serum and liver RPI activity increased in rats with hepatoma induced by 3'-Me-DAB. 4) An increase in serum RPI activity was seen in higher percentage in cancer patients. Higher enzyme activity and its higher incidence were observed in patients with hepatic metastasis or primary hepatoma than in patients without metastasis. From these results it is concluded that serum RPI activity as a diagnostic aid is useful in estimating clinical course of hepatic disorders and also in diagnosing malignant tumors, especially in substantiating a diagnosis of metastasis to the liver.
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PMID:[Experimental and clinical studies on ribosephosphate isomerase (author's transl)]. 52 26

Eight LF x ICIG cell hybrid clones, isolated upon fusion of normal ICIG-7 human fibroblasts with tumorigenic, non-metastatic LF Cl.2A cells derived from a DAB-induced rat hepatocarcinoma, were studied. They were all highly tumorigenic and were capable of developing spontaneous lung metastases in syngeneic animals. All the hybrids were characterized by a rapid loss of human chromosomes. However, in long-term culture, they all revealed a persistence of human genetic information as assessed by Southern blotting. In hybrid lines in which human chromosomes were still visible, the most recurrent were numbers 7 and 9. Neither chromosome 7, previously reported to bear some of the genes controlling metastasis in human X mouse T-cell hybrids, nor chromosome 9 appeared to be correlated with the metastatic potential of LF X ICIG hybrids. The same conclusion applied (1) to a human 3.3-kb EcoRI DNA fragment which was amplified (approx. 10-fold) only in metastases induced by one out of 3 metastatic hybrids tested; (2) to the transcription level of c-Ha-ras and c-Ki-ras genes which was enhanced (approx. 4-fold) in metastatic and non-metastatic lines as well. Co-transfection of LF Cl.2A cells with pHSG 272 selectable marker DNA and genomic DNA from normal ICIG-7 human cells or from a hybrid-induced metastasis, reproducibly gave rise to geneticin-resistant transfectants capable of producing spontaneous lung metastases. Neither transfectants nor transfectant-induced metastases harbored detectable human DNA sequences but all harbored pHSG 272 DNA. These results again call for caution in gene transfer studies of the metastatic process.
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PMID:Spontaneous metastatic potential of rat hepatocarcinoma cells after cell fusion or DNA transfection. 130 25

The dynamic changes of fibronectin (FN) content and nuclear features (DNA content, morphological parameters) during the development of hepatoma induced by 3'-Me-DAB were studied via computer-assisted image analysis. The results showed that the amount of FN decreased progressively and even disappeared completely during hepatocarcinogenesis. The difference between distinctive foci or nodules was highly significant (P less than 0.0001) and the DNA content was also increased coincidently during the same process.
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PMID:[Dynamic changes of fibronectin, DNA and morphology of the nuclei of experimental hepatoma in rats]. 149 77

The mechanism of glucose transported (GT) expression on the plasma membranes of hepatoma cells in rats induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) was studied. Cytochalasin B binding to plasma membrane fractions from control and 3'-MeDAB group in the absence of cold cytochalasin B showed 9,825 +/- 925 and 30,165 +/- 625 dpm/mg membrane protein. Scatchard plot analysis showed that the GTs present on the plasma membrane fractions in control and 3'-Me DAB groups were 5.0 and 16.0 pmol/mg membrane protein and their Kd values were 151 and 157 nM, respectively. These results suggest that the numbers of GTs in plasma membrane were increased in the 3'-Me DAB group compared to the control group. In contrast, the amounts of GTs in low density microsomal (LDM) fractions measured by a photoaffinity labeling technique using [3H]-cytochalasin B were 31,207 and 11,702 dpm/mg protein in the control and 3'-Me DAB group, respectively. These results suggest that GTs were translocated from LDM to plasma membranes during carcinogenesis. To confirm these results by an independent method 10% SDS-polyacrylamide gel electrophoresis was carried out. Gel slice No. 13 corresponding to MW of 45 kDa from plasma membrane fractions showed increased radioactivities in the 3'-Me DAB group compared to the control group. However, LDM fractions of the 3'-Me DAB group showed decreased radioactivities compared to the control group. Western blot analysis using anti-human RBC GT antibody present in the plasma membranes and LDM fractions from control and 3'-Me DAB groups did not show any significant difference, indicating low cross-reactivity between them. These results indicate that increased glucose transport seems to be more likely due to reciprocal redistribution of GTs between plasma membrane and LDM fractions.
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PMID:A study on the regulation of translocation of glucose transporters during hepatocarcinogenesis induced by 3'-Me DAB. 207 56

In a DAB-hepatoma organic tumor, Ga-67 accumulated markedly in the hepatocellular carcinoma with scant stroma but not in the cholangioma that was rich in connective tissue. No granulation tissue was formed around the tumor. In transplanted tumors (Ehrlich's tumor and Sarcoma 180), Ga-67 accumulated in the granulation tissue within the fibroblasts, leukocytes and capillaries surrounding the tumor, rather than in the tumor. In inflammatory lesions, Ga-67 uptake was similar in granulation tissue with large numbers of phagocytes, such as leukocytes and histiocytes, and capillaries. There was a very good correlation between the degree of Ga-67 uptake and of cellular infiltration and the proliferation of capillaries. Ga-67 uptake, both in inflammatory lesions and in transplanted tumors, was observed in the granulation tissue. This result implies that the mechanisms of Ga-67 uptake in tumor and inflammatory tissues are not the same, because Ga-67 accumulated in the DAB-hepatoma that had no inflammatory granulation tissue. This study indicates that a non-transplanted tumor is required to study Ga-67 accumulation in tumors, as different results may occur in tumors with and without inflammatory granulation tissue.
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PMID:Gallium-67 citrate uptake in experimental tumors and inflammatory lesions--an histo-autoradiographic correlation. 225 80

We investigated alpha-fetoprotein (AFP)-positive cells in 3'-Me-DAB hepatocarcinogenesis. In the early stage of 3'-Me-DAB hepatocarcinogenesis immunoreaction of AFP was detected in proliferating cholangiolar "oval" cells and in the late stage, AFP-positive cells, differing from oval cells, were detected in clusters in rat liver with hyperplastic nodules. The clusters of AFP-positive cells were morphologically classified into two different types of foci and one type of nodule. The combined techniques of immunocytochemistry and ratioautography revealed that AFP-positive foci and nodule had more 3H-thymidine labeling index than did areas without AFP-positive cells in liver with hyperplastic nodules; also one type of AFP-positive foci had a higher labeling index than the other type and in AFP-positive nodules there was active cell proliferation; but AFP-positive foci or nodules had less 3H-thymidine labeling than AFP-positive hepatoma cells. These findings suggested that AFP-positive foci and nodule had different biological significance in development of hepatocellular carcinoma and that AFP-positive foci with higher labeling index and AFP-positive nodule should be surveyed as preneoplastic population.
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PMID:Biological significance of AFP-positive cells in rat livers with hyperplastic nodules induced by 3'-Me-DAB; combined immunocytochemical and radioautographical studies. 243 6

Aldolase A, B, and C were determined in rat liver and serum by radioimmunoassay (RIA) in order to evaluate the alteration of these isozymes in the process of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), and the immunohistochemical technique was also used for the analysis of localization of aldolase isozymes. Aldolase A was increased in cancer tissues of 3'-Me-DAB induced hepatoma, whereas aldolase B was decreased in the same tissues according to both RIA and the immunohistochemical technique. During the promotion stage of hepatocarcinogenesis, the cells in hyperplastic nodules, which are known as preneoplastic lesions, were stained for aldolase A. Aldolase C was slightly increased in cancer tissues by RIA, suggesting the increase of A-C hybrid like A3C which was demonstrated by the electrophoretic method. Serum aldolase A levels were not significantly elevated in rats with liver cancer in comparison to rats with non-cancer.
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PMID:[Biochemical and immunohistochemical studies on alteration of aldolase isozymes in rat liver in the process of hepatocarcinogenesis by administration of a diet containing 3'-methyl-4-dimethylaminoazobenzene]. 251 Nov 29

To determine whether or not the cytotoxic effects of hyperthermia are directed primarily to malignant cells, we examined changes in thermosensitivity during hepatocarcinogenesis in rats, as induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The findings were compared with those in livers of rats fed a commercial diet. The cell viability was determined using the succinate dehydrogenase inhibition (SDI) test. The succinate dehydrogenase (SD) activity of liver cells, when exposed to heat (43 degrees C) for 2, 5, or 10 hr, decreased in a time-dependent manner, in each tissue. The decrease in SD activity was evident in 3'-Me-DAB liver for 5 hr of heat treatment on day 57, compared with findings in the normal liver. Significant differences were present for 2, 5, and 10 hr on days 93 and 136. Thus a chemically induced hepatoma is more sensitive to heat than are the normal cells. As this thermosensitivity gradually increased during the hepatocarcinogenesis, the malignant cells are particularly vulnerable to hyperthermia.
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PMID:Azo-dye-induced primary hepatoma and a gradual increase in thermosensitivity. 279 54

Immunohistochemical localization of gamma-glutamyl transpeptidase (gamma-GTP) in rat liver during 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) hepatocarcinogenesis was investigated and compared with sites of gamma-GTP activity. Immunohistochemically, gamma-GTP was stained in the apical border of proliferating oval cells during the early stages of azo-dye carcinogen feeding. After 7 weeks, multiple hyperplastic nodules appeared in which gamma-GTP was localized in the bile canaliculi. In hepatoma tissues, positive staining for gamma-GTP was observed in the bile canaliculi-like spaces, on the cell membrane, and sometimes in the cytoplasm of malignant cells. Enzyme histochemical staining showed gamma-GTP activity to be present in almost the same areas as the immunoreactive gamma-GTP. However, some areas adjacent to hepatoma tissue showed immunohistochemically reactive protein but no enzyme activity. Immunoreactive gamma-GTP was present in all locations at which enzyme activity was seen. The present data suggest that an altered form of gamma-GTP might be present in tissues during 3'-Me-DAB hepatocarcinogenesis.
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PMID:gamma-Glutamyl transpeptidase in rat liver during 3'-Me-DAB hepatocarcinogenesis: immunohistochemical and enzyme histochemical study. 287 49


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