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)

alpha-Fetoproteins (AFPs) were purified from 2 hepatoma cell lines (Hep G2 and HuH-7) and a hepatoblastoma cell line (HuH-6), and the structures of pyridylaminated (PA) derivatives of their sugar chains were analyzed by HPLC. Simultaneously, the activities of alpha 1-6 fucosyltransferase (alpha 1-6FT) and N-acetylglucosaminyltransferase III (GnT-III), IV (GnT-IV) and V (GnT-V) were assayed in these cell lines. For all 3 cell lines the major sugar chain detected was a fucosylated biantennary structure. Hep G2 cells contained a high level of GnT-V, which catalyzes the formation of a tri'-antennary structure, and in fact a substantial percentage of the AFP sugar chains in these cells had the tri'-antennary structure. alpha 1-6FT was also high, and fucosylated tri' structures were detected, which suggests that high activities of transferases affect the AFP sugar chains. In HuH-6 cells, GnT-III, which catalyzes the formation of bisecting GlcNAc, was elevated. Correspondingly, a fucosylated, bisected biantennary structure was found as a major sugar chain. In the HuH-7 cell line, the contents of bisecting GlcNAc and tri' structure were low and neither GnT-III nor GnT-V was elevated. These data indicate that the sugar structures of AFP in these cell lines correlate well with the activities of alpha 1-6 FT, GnT-III and GnT-V.
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PMID:Enzymatic basis of sugar structures of alpha-fetoprotein in hepatoma and hepatoblastoma cell lines: correlation with activities of alpha 1-6 fucosyltransferase and N-acetylglucosaminyltransferases III and V. 137 6

The immunohistochemical detection of the c-erbB-2 oncopeptide (p185erbB2) has been shown to be a valid marker for over-expression of this oncogene. To evaluate the possible relevance of gene expression to the proliferation of hepatocytes and bile ducts in human disease, the authors applied a monoclonal anti-p185 antibody to formalin-fixed, paraffin-embedded tissues from 67 examples of benign proliferative and neoplastic hepatic lesions and fetal liver. Focal membrane-based reactivity for the oncopeptide was detected on tumor cells in two of eight hepatocellular carcinomas and on tumor cells and adjacent bile ducts and hepatocytes in four of six cholangiocarcinomas. Each of the latter four lesions were in patients with primary sclerosing cholangitis. No reactivity was obtained in examples of hepatoblastoma, mixed cholangiocarcinoma-hepatocellular carcinoma, bile duct adenoma, or hepatocellular adenoma. Weak staining for p185erbB2 also was seen in two of seven cases of (sub)massive hepatic necrosis and two examples of postnecrotic cirrhosis, all of which were secondary to either hepatitis B or C virus infection. No other benign proliferative lesions were labeled by the anti-p185 antibody, including cases of chronic allograft rejection, necrosis secondary to hepatic artery thrombosis, metabolic-associated and nonmetabolic-associated cirrhosis, focal nodular hyperplasia, and nodular regenerative hyperplasia. The authors' results indicate that c-erbB-2 may be amplified in specific neoplastic and hepatitis B virus and hepatitis C virus infectious lesions of liver. The authors postulate that: (1) c-erbB-2 immunoreactivity may be a marker for malignant transformation in primary sclerosing cholangitis; and 2) overproduction of p185erbB2 may be an epiphenomenon of hepatitis B virus or hepatitis C virus infection.
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PMID:Immunoreactivity for c-erbB-2 oncopeptide in benign and malignant diseases of the liver. 137 19

The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.
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PMID:Immunotargeting chemotherapy for AFP-producing pediatric liver cancer using the conjugates of anti-AFP antibody and anti-tumor agents. 138 75

After a pilot phase in 1988 the liver tumour study HB-89 of the German Society of Pediatric Oncology and Hematology (GPOH) was started on January 1st 1989. It comprises the malignant epithelial liver tumours of childhood--hepatoblastoma and hepatocellular carcinoma. The objectives of the study are 1. to reduce surgical complications and incomplete tumour resections by restricting the primary operation to a lobectomy of the liver in case of small tumours or to a biopsy in case of extended disease, and 2. to reduce the size of large tumours by means of chemotherapy for subsequent resection. The tumourreductive and adjuvant chemotherapy consists of the combinations of ifosfamide, cisplatinum, adriamycin (IPA) and cisplatinum plus adriamycin as continuous infusion (PA-cont). Up to December 31st 1991 a total of 78 pediatric liver tumours were registered, 51 of those hepatoblastomas and 10 hepatocellular carcinomas. 19 (37%) hepatoblastomas were resected at primary operation (stage I and II). After chemotherapy 24 (83%) of 29 primarily inoperable hepatoblastomas (stage III and IV) became resectable, one child received a liver transplant. At the time all hepatoblastoma patients of stages I and II and 20 (69%) of stages III and IV are in remission, the overall remission rate is 81% (39/48). Seven patients with multifocal hepatoblastoma had an unfavourable outcome, only two are free of tumour. Of 10 patients with a hepatocellular carcinoma only three with a primary complete tumour resection are disease free. The IPA and PA-cont therapies were highly effective on hepatoblastomas (96%), but not on hepatocellular carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapy of malignant liver tumors in childhood. An intermediate report of the HB-89 multicenter study of the GPOH]. 138 54

After completion of a pilot phase in 1988, the liver tumour study HB89 of the German Society of Paediatric Oncology started on January 1st, 1989. Up to the end of 1990, 54 children with a primary tumour of the liver where enrolled into the study. Thirty-six of them suffered from hepatoblastoma, 8 from hepatocarcinoma. Thirteen of the hepatoblastomas could be resected primarily, 17 were removed following preoperative chemotherapy. One patient with a stage III hepatoblastoma underwent successfully liver transplantation. At the end of 1990, 28 patients were in first remission (78%), two were still under chemotherapy, and six had died after tumour progression or relapse. Out of eight patients with hepatocarcinoma, only two with a primarily resected tumour are still in first remission. Chemotherapy with ifosfamide, cis-platinum, and adriamycin (IPA) or with continuous infusion of cis-platinum and adriamycin (PAcont) was effective in hepatoblastomas but not in hepatocarcinomas. Because of the problems of preoperative differential diagnosis and judgement of resectability, a primary laparotomy with an open tumour biopsy is necessary. Following the HB89 study protocol with its strategy of graded surgical treatment, the rate of resection was high, the perioperative morbidity low, and no death due to surgery was observed.
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PMID:[HB89: the liver tumor study of the Society for Paediatric Oncology. An interim report]. 155 1

The histological and ultrastructural features of oncogene transformed rat liver epithelial (RLE) cells in culture and spontaneously transformed RLE cells were studied. The tumours produced in nude mice by all the transformed cells were either moderately well differentiated carcinomas or sarcomatous tumours. Epithelial tumours were produced in the RLE cells after transduction of both v-raf and v-myc oncogenes whereas sarcomatous tumours were produced after transduction of v-raf alone. These data suggested that transformation of RLE cells with a single oncogene, v-raf, produced malignant tumours which were consistent with sarcomas while a combination of two oncogenes, v-raf and v-myc, produced an epithelial tumour, consistent with a carcinoma. The effects of these oncogenes on RLE cells indicate that they were able to differentiate and were capable of producing two morphologically distinct tumour types. The possible role of v-myc in switching the sarcomatous lineage to an epithelial tumour lineage is considered to be significant and worthy of further studies. The epithelial tumour produced in RLE cells by combination of v-raf and v-myc is consistent with an embryonal type of hepatoblastoma. The trabecular type of liver cell carcinoma which resulted from spontaneous transformation of RLE cells illustrates the inherent potential of the RLE cell to undergo malignant change and strongly suggests that the RLE cells may be the precursor cells in the development of hepatocellular carcinoma in the rat.
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PMID:Pathology of spontaneous and oncogene transformed rat liver epithelial cells and derived tumours in nude mice. 157 82

Primary tumors of the liver that are of clinical significance are rare. Ninety-five percent of such lesions when encountered will be malignant and only 5% will be benign. Malignant primary hepatic lesions represent 2% to 3% of primary cancers encountered in the United States. Hepatocellular carcinoma constitutes 90% of malignant liver primaries in the adult. Seventy-five percent of cases are associated with cirrhosis of the liver and patients with hepatitis B infection have a 33- to 200-fold excess risk for this malignancy. Cholangiocarcinoma represents 5% to 10% of hepatic primary malignancies while hepatoblastoma is distinctly uncommon in adults. Treatment is primarily surgical, and resectability is limited by the presence of cirrhosis and spread of the tumor within and outside of the liver. Of the benign liver tumors, the liver cell adenoma seem to be associated with oral contraception and have a proclivity for intraperitoneal hemorrhage, especially during pregnancy. Focal nodular hyperplasia is a tumor-like condition that also may be associated with oral contraception. This article describes five cases, two of which had quite unique presentations.
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PMID:Primary tumors of the liver. 160 11

Cytogenetic analysis of eight human hepatoma-derived cell lines and one primary hepatocellular carcinoma biopsy revealed multiple chromosome abnormalities; however, only chromosome 1 was consistently affected by rearrangements. Pseudopolysomy 1 as well as chromosome 1 deletions and/or translocations that resulted in loss of the distal 1p region from at least one copy of chromosome 1 were observed in all but one of the cell lines analysed. Molecular analyses of tumor-derived and normal genomic DNA from six cases of hepatocellular carcinoma and from two of hepatoblastoma, using a panel of chromosome 1p-specific DNA probes indicated allelic loss in the distal 1p region in five of the six hepatocellular carcinomas but not in either hepatoblastoma. These results suggest the location of a gene in the distal 1p region whose functional loss may be involved in hepatocellular carcinogenesis.
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PMID:Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas. 164 86

NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein which catalyzes the two-electron reduction of quinones and azo-dyes and thus prevents the formation of free radicals and toxic oxygen metabolites that may be generated by the one-electron reductions catalyzed by cytochrome P450 reductase. Analysis of RNA indicated 20- to 50-fold higher levels of NQO1 gene expression in the liver tumors and in the tissue surrounding the tumors of patients with hepatocarcinoma than in normal individuals. An approximately 50-fold higher level of NQO1 mRNA was also observed in human hepatoblastoma (Hep-G2) cells than in normal liver. By deletion mutagenesis in the human NQO1 gene promoter and subsequent transfection into hepatic and nonhepatic cell lines, a 1.42 kb DNA segment has been identified to contain cis-acting elements responsible for high levels of expression of the NQO1 gene in tumor cells.
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PMID:High levels of expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene in tumor cells compared to normal cells of the same origin. 165 29

The mechanisms which control the production of erythropoietin (Epo) remain enigmatic. Recent data suggest that the half-time of Epo messenger RNA (mRNA) is increased by hypoxia in Hep 3B cells, a human hepatoma line. The post-transcriptional regulation of other rapidly degraded mRNAs is mediated by sequence-specific mRNA binding proteins. In order to determine if Epo mRNA specific binding proteins exist, we probed cytosolic lysates from Hep 3B cells and mouse tissues with radiolabeled Epo RNA. A cytosolic protein that binds specifically to Epo RNA was identified in the Epo-producing, hepatoblastoma Hep 3B cell line by gel mobility shift assay. This protein was identified in both normoxic and hypoxic cells and bound specifically to a 120-base fragment of the 3'-untranslated region (3'-UTR) of Epo mRNA. Binding was completed with unlabeled Epo RNA, but not with granulocyte-macrophage colony-stimulating factor RNA. Ultraviolet light cross-linked Epo RNA-protein complexes migrated as two bands of 70 and 135-140 kD on sodium dodecyl sulfate-polyacrylamide gels. Binding activity was markedly increased in brain and spleen lysates from mice subjected to 24 h of hypoxia. Therefore, the post-transcriptional regulation of Epo expression in response to hypoxia may in part be due to the interaction of Epo RNA with its specific binding protein.
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PMID:Hypoxia up-regulates the activity of a novel erythropoietin mRNA binding protein. 165 42


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