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)

Changes of nucleotide sequences and expressions of cellular oncogenes in human hepatoma cell lines, PLC/PRF/5, HCC-M and HCC-T cells, were examined by Southern and Northern blot analyses. The probes used are DNA fragment of myc, N-, H-, K-ras, fos, fms, raf, erb-A, erb-B, and erb-B2 genes and synthetic oligonucleotides corresponding to the part of N-, H-, K-ras genes. The results are as follows. DNA amplification and rearrangement were not detected in these three human hepatoma cell lines. Point mutations at codons 12, 13, and 61 in N- and K-ras genes were not demonstrated in these cell lines. N-, H-, K-ras and myc transcripts were detected in these three cell lines. However, fos gene transcript was detected only in PLC/PRF/5 and HCC-M cells which were derived from hepatitis B related hepatocellular carcinoma and having integrated hepatitis B virus (HBV) DNA. These data showed that there are no specific proto-oncogene expression into RNA except for myc and ras genes, nor DNA rearrangement in these 3 human hepatoma cell lines with regards to at least 10 different oncogenes examined and suggest the relationship between fos gene expression and integration of HBV DNA in host cell DNA.
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PMID:Proto-oncogene expression in three human hepatoma cell lines, HCC-M, HCC-T and PLC/PRF/5. 166 47

We investigated the presence of the hepatitis C virus (HCV) genome in liver tissues of eight different patients with hepatocellular carcinoma by using the reverse transcriptase polymerase chain reaction (PCR) method. RNA was extracted separately from cancerous and peripheral noncancerous portions of the liver tissues of each patient. For reverse transcriptase PCR, we used sets of primers derived either from nonstructural region 3 (the NS3 region) or from the nucleocapsid-envelope (C/E) region of the HCV genome. The nucleotide sequences of the amplimers were directly determined without subcloning. Of 16 samples tested, cDNA of the HCV genome was detected in 2 cancerous tissues and in 4 noncancerous tissues by either pair of primers. Nucleotide sequences of HCV cDNA fragments amplified from cancerous and peripheral noncancerous tissues from the same patients were identical. However, 4.4 to 6.3% and 7.5 to 11.3% sequence variation was observed in NS3 and C/E regions, respectively, among cDNA fragments from different patients. The result indicated that the HCV genome detected in a given patient is distinguishable from that in others by a simple direct nucleotide sequencing of the reverse transcriptase PCR products.
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PMID:Discrimination of hepatitis C virus in liver tissues from different patients with hepatocellular carcinomas by direct nucleotide sequencing of amplified cDNA of the viral genome. 166 47

We studied the effects of transfection of the normal c-Ha-ras gene, rasGly-12, and its oncogenic mutant, rasVal-12, on expression of the alpha-fetoprotein (AFP) and albumin genes in a human hepatoma cell line, HuH-7. The mutant and, to a lesser extent, the normal ras gene caused reduction of the AFP mRNA but not the albumin mRNA level in transfected HuH-7 cells. Cotransfection experiments with a rasVal-12 expression plasmid and a chloramphenicol acetyltransferase reporter gene fused to AFP regulatory sequences showed that rasVal-12 suppressed the activity of enhancer and promoter regions containing A + T-rich sequences (AT motif). In contrast, rasVal-12 did not affect the promoter activity of the albumin and human hepatitis B virus pre-S1 genes even though these promoters contain homologous A + T-rich elements. ras transfection appeared to induce phosphorylation of nuclear proteins that interact with the AFP AT motif, since gel mobility analysis revealed the formation of slow-moving complexes which was reversed by phosphatase treatment. However, similar changes in complex formation were observed with the albumin and hepatitis B surface antigen pre-S1 promoters. Therefore, this effect alone cannot explain the specific down regulation of the AFP promoter and enhancer activity. ras-mediated suppression of the AFP gene may reflect the process of developmental gene regulation in which AFP gene transcription is controlled by a G-protein-linked signal transduction cascade triggered by external growth stimuli.
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PMID:c-Ha-ras down regulates the alpha-fetoprotein gene but not the albumin gene in human hepatoma cells. 169 Aug 41

To elucidate the cell biological significance of ras oncogene, the expression of ras-p21 was analyzed in 53 cases of liver tissues including 34 cases of hepatocellular carcinoma (HCC), by using immunohistochemical method. In result, 22 (65%) cases of 34 HCC and 34 (79%) cases of 43 liver cirrhosis were positive for p21, whereas all of chronic hepatitis and normal livers were negative. Especially, comparative study between the expression of p21 and clinicopathological background of HCC revealed that p21 was prominently expressed in well differentiated form, nodular type, small liver cancer, and the cases showing AFP levels below 400 ng/ml. From these results, it was indicated that ras oncogene might play an important role in malignant transformation of hepatocytes or differentiation of HCC.
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PMID:[The expression of ras p21 product in hepatocellular carcinoma]. 170 Jan 76

LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations were observed, suggesting that ras activation is not involved in spontaneous hepatocarcinogenesis in LEC rats. The expression of mRNAs for c-myc, Ha-ras, c-raf, and the protein phosphatase 2A alpha gene (PP-2A alpha) was also examined in the four HCCs by northern blot analysis. Three of the four HCCs had c-myc expression levels approximately 30-fold higher than that in the liver of control Long-Evans rats with an agouti coat color (LEA), a sibling line of LEC rats, while the remaining HCC had an expression level sevenfold higher than that of control. In contrast, the expression levels of the Ha-ras, c-raf, and PP-2A alpha genes were the same as those in the livers of control rats. Studies of c-myc expression and mitotic index in five other HCCs, two hyperplastic nodules, and two nontumorous portions of livers of HCC-bearing LEC rats that had chronic-phase hepatitis suggested that the high level of c-myc gene expression was not due only to increased cell proliferation but might possibly be more integrally involved in hepatocarcinogenesis.
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PMID:Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats. 171 40

Pathological diagnosis of hepatic tumors is sometimes difficult when performed with only routine examinations such as Hematoxylin and Eosin (H.E.) stain. The diagnostic usefulness of KM01 was compared to that of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9 and ras p21 in this immunohistochemical study. AFP was positive in about half of the cases of hepatocellular carcinoma and hepatoblastoma, and AFP-positive cells were frequently found at the periphery of acini in both diseases. Absorbed CEA stain was mostly negative in hepatocellular carcinoma, but was positive in the cells of mixed hepatocellular and cholangiocellular carcinoma (MHCC) and metastatic liver cancer, especially in their cytoplasm. CA19-9 immunostaining was completely negative, and was only 3% positive in hepatocellular carcinoma. KM01 stain was positive in about half of the cases of hepatocellular carcinoma, hepatoblastoma and MHCC. It was positive in proliferated bile ducts around the capsule in the former two diseases but positive in the tumor cell of both parts of the cytoplasm in the latter. The histological positivity of ras p21 was high in all tumor cells of these three types of tumors. Negative absorbed CEA and KM01 in pseudoglandular hepatocellular carcinoma differentiated from MHCC and metastatic liver cancer. However these tumor markers were occasionally positive and nonspecific in cancer-like lesions, implying no advantage for differential diagnosis between hepatocellular carcinoma and apparent cancer-like lesions. The above results demonstrate that AFP, CEA and KM01 are effective for differentiating hepatocellular carcinoma among various hepatic tumors.
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PMID:Immunohistochemical study on hepatic tumors--KM01 stains compared with AFP, CEA, CA19-9 and RAS P21. 171 40

A detection system was developed to distinguish the four different HCV genomes [HCV-J, HCV-US, HCV-K2 and group II HCV (HCV-GII)], involving reverse transcription followed by a nested polymerase chain reaction using specific primers for each HCV type. The putative non-structural (NS) 5 regions of HCV-J, HCV-US and HCV-K2 and the putative NS3 region of HCV-GII were amplified. Of 95 specimens from patients with acute hepatitis, chronic hepatitis, liver cirrhosis or hepatocellular carcinoma, 67 specimens were positive for HCV-J, 2 for HCV-US, 23 for HCV-K2 and 11 for HCV-GII. About half the specimens that were positive for HCV-K2 or HCV-GII were coinfected with HCV-J and all those that were positive for HCV-GII were also positive for HCV-K2. Nucleotide sequence analysis of several amplified cDNA products revealed that HCV-K2 and HCV-GII could each be classified into two groups, and the pattern of classification of HCV-K2 was identical with that of HCV-GII. Therefore, our results strongly suggest that HCV-K2 is the same as HCV-GII.
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PMID:Distribution of plural HCV types in Japan. 172 Mar 9

An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.
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PMID:Regulation of de novo and salvage pathways in chemotherapy. 187 99

The male hybrid B6C3F1 mouse exhibits a 30% spontaneous hepatoma incidence, whereas the paternal C3H/He strain and the maternal C57BL/6 strain exhibit a 60% and a negligible incidence, respectively. In addition, both male and female B6C3F1 mice are extremely sensitive to chemical induction of hepatocarcinogenesis. The Ha-ras, Ki-ras, and myc oncogenes have been implicated in a variety of solid tumors. Specifically, Ha- and, less frequently, Ki-ras have been reported to be activated in B6C3F1 mouse liver tumors. The objective of this study was to examine a possible point of transcriptional control of Ha-ras, Ki-ras, and myc in all three mouse strains, our hypothesis being that these oncogenes may be primed for expression in the nascent liver of those strains exhibiting a high spontaneous hepatoma incidence. A positive correlation has been established between gene expression and the presence of DNase I hypersensitive sites. DNase I hypersensitive sites were observed in the Ha-ras and myc oncogenes in the three mouse strains. However, Ha-ras appears to possess an additional site in B6C3F1 and C3H/He as compared to C57BL/6. Similarly, the Ki-ras oncogene exhibited a DNase I hypersensitive site only in B6C3F1 and C3H/He mouse liver. These results indicate that the hepatoma-prone strains (B6C3F1 and C3H/He) may have a greater potential for Ha- and Ki-ras expression than does the non-hepatoma-prone strain (C57BL/6).
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PMID:Differential DNase I hypersensitivity of ras oncogenes in B6C3F1, C3H/He, and C57BL/6 mouse liver. 194 24

With dot blot and cytoplasmic hybridization techniques we found that the c-Ha-ras, c-Ki-ras, c-N-ras, c-myc and c-fos oncogenes were over-expressed in human hepatocellular carcinoma cell line BEL 7402 cells. The mRNA expression of c-Ha-ras, c-Ki-ras, c-N-ras and c-myc oncogenes could be inhibited by 2 mmol/L sodium butyrate treatment, but this had no effect on the expression of c-fos. However, the mRNA expression of c-Ha-ras, c-N-Ras and c-myc oncogenes was enhanced by 4 mmol/L sodium butyrate treatment, while the expression of c-Ki-ras and c-fos remained unchanged. No significant effect on the expression of carbamyl phosphate synthetase I, a tissue-specific enzyme associated with the differentiation of liver cells, was observed by 2 mmol/L or 4 mmol/L sodium butyrate treatment of the hepatoma cells.
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PMID:[Expression of cellular oncogenes in human hepatocellular carcinoma cell line BEL 7402 and the effect of sodium butyrate on the expression of cellular oncogenes]. 196 12


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