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)

Focal nodular hyperplasia of the liver is a lesion characterized by a well-circumscribed region of hyperplastic liver parenchyma and contains a stellate fibrous scar. The lesion is thought to be because of liver-cell hyperplasia that is caused by focal circulatory disturbances. We describe here a pediatric case of this lesion that provided direct histopathologic evidence of circulatory disturbances. We identified arterial and portal thrombi, as well as recanalization of arteries in the nodule. Hepatic necrosis was also seen in the lesion. We speculate that thrombosis of the hepatic artery and/or portal vein was the cause of hepatic necrosis and that reperfusion following hepatic arterial recanalization resulted in nodule formation. Although there was no stellate scar present in our case, the presence of bile ductular proliferation at the periphery of the nodule was helpful in distinguishing this lesion from adenoma and hepatocellular carcinoma. The early stage of nodular formation may explain the lack of a stellate scar in our case. The patient was treated earlier with actinomycin D and vincristine following surgical excision of Wilms' tumor. It is possible that such chemotherapy contributed to thrombosis in our case.
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PMID:Focal nodular hyperplasia of the liver: direct evidence of circulatory disturbances. 1112 13

CCN family genes, Nov, CYR61 and CTGF, are immediate-early genes expressed in fibroblasts following growth stimuli. Aberrant expression of Nov has been found in human Wilms' tumor, and suggested to be involved in tumorigenesis. The aim of our experiments is to examine the expression of CCN family genes in human hepatocellular carcinomas (HCCs) and find the correlation of these gene expressions with clinicopathological parameters. A pair of tumor and surrounding non-tumor tissues were obtained from 23 patients with HCC and six with metastatic liver tumor. Total cellular RNA isolated from tissues was analyzed for the presence of mRNA of CCN family genes by the reverse-transcription polymerase chain reaction. Nov, CYR61 and CTGF mRNA were identified in 17 (73.9%), 17 (73.9%), six (26.1%) tumors, and in nine (39.1%), 16 (69.6%), one (4.3%) surrounding non-tumor tissues of 23 patients with HCC. No significant difference was found in clinicopathological parameters between cases with HCC negative and positive for these gene expressions. The prevalence of Nov and CTGF expression in HCC is significantly higher than those in surrounding non-tumor. The same tendency was found in metastatic tumors. These results suggest that Nov and CTGF is associated with the development of tumors in the liver.
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PMID:Expression of Nov, CYR61 and CTGF genes in human hepatocellular carcinoma. 1125 12

Contents of sphingenine (sphingosine) and sphinganine were studied in sphingomyelins of transplantable mouse tumors (hepatoma-22, melanoma B16, Lewis lung carcinoma, intestine carcinoma) and rat nephroma RA. The content of sphinganine was increased in sphingomyelins of hepatoma-22 and nephroma RA compared to sphingomyelins of liver and kidneys. Significant contents of sphinganine were also found in sphingomyelins of other studied tumors. The content of sphinganine in regenerating mouse liver (30 h after hepatectomy) was normal. The data suggest that disorders should exist in biosynthesis of sphingoid bases in tumors but not in normal rapidly proliferating tissue.
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PMID:Sphinganine in sphingomyelins of tumors and mouse regenerating liver. 1140 84

AIM:To analyse cumulative loss of heterozygosity (LOH) of chromosomal regions and tumor suppressor genes in hepatocellular carcinomas (HCCs) from 20 southern African blacks.METHODS: p53,RB1, BRCA1, BRCA2, WT1 and E-cadherin genes were analysed for LOH, and p53 gene was also analysed for the codon 249 mutation, in tumor and adjacent non tumorous liver tissues using molecular techniques and 10 polymorphic microsatellite markers.RESULTS:p53 codon 249 mutation was found in 25% of the subjects,as was expected, because many patients were from Mozambique, a country with high aflatoxin B-1 exposure. LOH was found at the RB1, BRCA2 and WT1 loci in 20%(4/20) of the HCCs, supporting a possible role of these genes in HCC. No LOH was evident in any of the remaining genes. Reports of mutations of p53 and RB1 genes in combination, described in other populations, were not confirmed in this study. Change in microsatellite repeat number was noted at 9/10 microsatellite loci in different HCCs, and changes at two or more loci were detected in 15%(3/20) of subjects.CONCLUSION:We propose that microsatellite/genomic instability may play a role in the pathogenesis of a subset of HCCs in black Africans.
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PMID:Characterization of six tumor suppressor genes and microsatellite instability in hepatocellular carcinoma in southern African blacks. 1181 94

The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS.
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PMID:Bloom syndrome in sibs: first reports of hepatocellular carcinoma and Wilms tumor with documented anaplasia and nephrogenic rests. 1182 67

Pulmonary surgery is frequently used for the treatment of metastasis or nodules in children with various types of malignancies. However, the indications and effectiveness of pulmonary metastatectomy have not been evaluated recently. Therefore, a retrospective study was conducted to analyse the results of pulmonary metastatectomy in children. Children who underwent pulmonary metastatectomy at our department between 1990 and 2000 were reviewed. Eighteen children consisting of 11 boys and 7 girls (age range, 3 to 18 years) underwent thoracotomy for pulmonary metastasis excision. The primaries were osteosarcoma (n = 2), synovial sarcoma (n = 1), fibrosarcoma (n = 1), Ewing's sarcoma (n = 2), mesenchymal chondrosarcoma (n = 1), Wilms' tumour (n = 4), clear-cell sarcoma (n = 1), Hodgkin lymphoma (n = 3), hepatoblastoma (n = 1), hepatocellular carcinoma (n = 1) and haemangioendotheliosarcoma (n = 1). Pulmonary metastases were encountered either at the time of initial diagnosis (22 %) or occurred within 6 months to 5 years. They were frequently nodular (94 %), unilateral (94 %) and located in the right lung (70 %). The number of metastases were frequently one (56 %) or two (28 %). Excision was done by means of wedge resection (88 %), segmentectomy (6 %), and lobectomy + wedge resection (6 %). The nodules contained tumour cells in most cases (n = 14) (78 %), mature nephrogenic elements (6 %) and no tumour tissue (16 %) in the remaining cases. Histology was similar to that of the original tumour in 12 cases. However, synovial sarcoma was encountered in metastasis in one case with fibrosarcoma primary. Re-thoracotomy was performed in 22 % of cases for the recurrent lesion, which in only one case was a true local recurrence. Overall disease-free survival rate was 56 % during the follow-up period (mean, 36.4 +/- 31.8 months). Pulmonary metastatectomy may increase survival in carefully selected children, though it is unlikely to cure the patient. Therefore combined therapies such as chemotherapy and/or radiotherapy should be continued in the postoperative period.
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PMID:Pulmonary metastases in children: an analysis of surgical spectrum. 1210 95

Many studies have associated chromosomal deletions in the 16q24 region with human cancers, including hepatocellular carcinoma. A more limited region around the microsatellite D16S402 has been shown implicated in the metastatic spread of hepatocellular carcinoma, prostate cancer, and Wilms' tumors. It is likely that one or more tumor suppressor genes are located in this 16q24 area. We used SYBR Green reagents to quantify, by real-time quantitative RT-PCR, the production of mRNA for 13 genes mapping to 16q24. The locations of these genes were determined from published human genome sequencing data. We studied mRNA levels in 10 liver tumor tissues, 10 nontumor liver tissues, five hepatoma cell lines, and in isolated hepatocytes. Results were compared with those for loss of heterozygosity observed in the D16S402 region and recurrence. No down-regulation was observed in tumor tissues. Two genes were consistently overexpressed: OKL38 and CDH13. CDH13, which functions in cell-cell adhesion, seems to be involved in liver carcinogenesis. However, no relationship was observed between the expression of this gene and changes in the D16S402 microsatellite or tumor recurrence. None of the other genes tested seemed to be a good candidate for a major tumor suppressor gene in liver carcinogenesis. Our results suggest that additional unknown genes involved in carcinogenesis are located in the 16q24 area.
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PMID:Investigation in liver tissues and cell lines of the transcription of 13 genes mapping to the 16q24 region that are frequently deleted in hepatocellular carcinoma. 1237 86

Hepatoblastomas (HBs) represent the most frequent malignant liver tumors of childhood; yet little is known about the molecular pathogenesis and the alterations in expression patterns of these tumors. We used a suppression subtractive hybridization approach to identify new candidate genes that may play a role in HB tumorigenesis. cDNA species derived from corresponding liver and fetal liver were subtracted from HB cDNAs, and a series of interesting candidates were isolated that were differentially expressed. One of the transcripts overexpressed in HB was derived from the human Dickkopf-1 (hDkk-1) gene, which encodes a secreted protein acting as a potent inhibitor of the wingless/WNT signaling pathway. We examined the hDkk-1 expression levels in 32 HB biopsy specimens and in the corresponding liver samples, in 4 HB cell lines, and in a panel of other tumors and normal tissues using a differential PCR approach and Northern blotting. Eighty-one percent of the HBs but none of the normal pediatric or fetal liver tissues showed hDkk-1 expression. hDkk-1 transcripts were also present in 5 of 6 Wilms' tumors but only weakly detectable in 2 of 20 hepatocellular carcinoma samples and in 1 of 5 medulloblastoma cell lines; transcripts were absent in malignant gliomas and breast cancer. The central effector molecule in the WNT developmental control pathway is the beta-catenin protein. Interestingly, activating mutations of the beta-catenin gene have previously been identified in 48% of HBs, and more than 85% of HBs show accumulation of beta-catenin protein as the indicator for an activated pathway. The overexpression of the inhibitor Dkk-1 may therefore be related to uncontrolled wingless/WNT signaling and may represent a negative feedback mechanism. hDkk-1 expression represents a novel marker for HBs and Wilms' tumors.
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PMID:Overexpression of human Dickkopf-1, an antagonist of wingless/WNT signaling, in human hepatoblastomas and Wilms' tumors. 1264 43

Glypican-3 (GPC3) encodes a cell-surface heparan- sulfate proteoglycan and its expression is frequently silenced in ovarian cancer, mesotheliomas, and breast cancer cell lines and ectopic expression of GPC3 inhibited the growth of these cells, suggesting that GPC3 plays a negative role in cell proliferation. In contrast, up-regulation of GPC3 is often observed in hepatoma, neuroblastoma, and Wilms' tumor. Whether GPC3 plays the same growth inhibitory role in these tumors remains to be studied. Here we report that antisense-mediated knockdown of GPC3 in the HepG2 hepatoma cells significantly promotes the growth of hepatoma cells. In addition, we show that this growth promotion is independent of insulin-like growth factor 2 (IGF2) signaling. Our data suggest that GPC3 plays a growth-suppressing role in hepatoma and provide cell biological evidence inconsistent with the hypothesis that GPC3 acts as a growth suppressor by downregulating IGF2.
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PMID:Growth promotion of HepG2 hepatoma cells by antisense-mediated knockdown of glypican-3 is independent of insulin-like growth factor 2 signaling. 1450 64

To determine the possible role of the epigenetic mechanisms in carcinogenesis of the hepatocellular carcinoma, we methylation-profiled the promoter CpG islands of twenty four genes both in HCC tumors and the neighboring non-cancerous tissues of twenty eight patients using the methylation-specific PCR (MSP) method in conjunction with the DNA sequencing. In comparison with the normal liver tissues from the healthy donors, it was found that while remained unmethylated the ABL, CAV, EPO, GATA3, LKB1, NEP, NFL, NIS and p27KIP1 genes, varying extents of the HCC specific hypermethylation were found associated with the ABO, AR, CSPG2, cyclin a1, DBCCR1, GALR2, IRF7, MGMT, MT1A, MYOD1, OCT6, p57KIP2, p73, WT1 genes, and demethylation with the MAGEA1 gene, respectively. Judged by whether the hypermethylated occurred in HCC more frequently than in their neighboring normal tissues, the hypermethylation status of the AR, DBCCR1, IRF7, OCT6, and p73 genes was considered as the event specific to the late stage, while that the rest that lacked such a distinguished contrast, as the event specific to the early stage of HCC carcinogenesis. Among all the clinical pathological parameters tested for the association with, the hypermethylation of the cyclin a1 gene was more prevalent in the non-cirrhosis group (P=0.021) while the hypermethylated p16INK4a gene was more common in the cirrhosis group (P=0.017). The concordant methylation behaviors of nineteen genes, including the four previously studied and their association with cirrhosis has been evaluated by the best subgroup selection method. The data presented in this report would enable us to shape our understanding of the mechanisms for the HCC specific loss of the epigenetic stability of the genome, as well as the strategy of developing the novel robust methylation based diagnostic and prognostic tools.
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PMID:Methylation profiling of twenty four genes and the concordant methylation behaviours of nineteen genes that may contribute to hepatocellular carcinogenesis. 1467 55


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