Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bcl-2 gene product (bcl-2 protein, BCLP) prevents apoptotic cell death. Via a 14;18 chromosomal translocation, BCLP is overexpressed in most follicular lymphomas as well as some other non-Hodgkin's lymphomas, and it has also been documented in other nonlymphomatous malignancies. To address the possible prognostic value of this marker in predefined subsets of non-small cell lung carcinoma (NSCLC), the authors studied 126 T1N0M0 cases seen between the years 1986 to 1991 at our institution. Patients were treated by lobectomy (105 cases) or wedge excision (21 cases) with negative margins; neuroendocrine carcinomas of all grades were specifically excluded. The mean follow-up period was 39 months. Immunostaining for BCLP was done using a monoclonal antibody (clone no. 124; DAKO, Carpinteria, CA), and the avidin-biotin-peroxidase complex (ABC) technique. The study cases included 73 adenocarcinomas (ACs) as well as 40 squamous cell (SCC), five adenosquamous (ASC), and eight large cell/poorly differentiated (LCC) carcinomas. As assessed with the Kaplan-Meier method, overall survival was 64% at 5 years (66% AC vs 59% SC). BCLP was detected in 47 of 126 cases (37%) including 32 AC (44%), 10 SCC 925%), two ASC (40%), and three LCC (38%). No significant difference in 5-year survival was noted in a comparison of all cases with BCLP expression (63%) and those without (59%). There was, however, a significant difference in the survival of grade 1 BCLP(+) cases, when compared with grade 2 or 3 BCLP(+) cases (P = .01). A nonstatistically significant trend toward increased survival was observed in BCLP(+) SCC cases (66% 5-year survival in BCLP[+] vs 45% in BCLP[-] [P = .11]). Proportional hazards analysis failed to disclose significant independent risk factors. These data suggest that bcl-2 protein immunoreactivity has limited prognostic value in the pathological evaluation of NSCLC.
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PMID:Expression of bcl-2 protein in stage T1N0M0 non-small cell lung carcinoma. 759 Jun 97

A series of 60 cases of oxyphilic (Hurthle cell) carcinomas (HCC) of the thyroid were reviewed to determine whether it is possible to correlate morphologic and clinical features as a means of assessing prognosis. Twenty cases showing predominant solid or trabecular patterns (as described in poorly differentiated carcinomas with a follicular pattern) were selected and the clinicopathological features were investigated. Based on cell size, two groups of solid or trabecular HCCs were identified: The first group (17 cases) was made up of typical large granular oxyphilic cells, and the second (three cases) had small oxyphilic cells. All tumors were reactive for thyroglobulin and for a mitochondrial antigen, selectively marking oxyphilic, mitochondrial-rich cells. Nuclear pleomorphism in individual cells was a common feature, but foci of anaplastic carcinoma were never found. Four cases overexpressed p53 protein and 10 expressed bcl-2 gene product. At follow-up, among the high-stage (pT3-pT4) tumors, seven patients had recurrences or metastases, six of whom were alive with disease or died of disease. In the control group of HCC with predominant follicular patterns, only one of 40 cases had a fatal outcome. The difference was statistically significant. Small-cell patterns and a p53 protein-positive/bcl-2 gene product negative phenotype were features of clinically aggressive HCC cases. We suggest that within the spectrum of oxyphilic (Hurthle cell) tumors, poorly differentiated HCC showing solid or trabecular patterns are a distinct group, based on both morphological and clinical features.
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PMID:Poorly differentiated oxyphilic (Hurthle cell) carcinomas of the thyroid. 865 47

We have demonstrated that sodium butyrate induces differentiation in human hepatoma cells; however, recent studies have shown that this agent causes apoptosis in some types of cancer cells. In this study, we examined whether sodium butyrate causes apoptosis in the human hepatoma cell lines, HCC-M and HCC-T. The growth of human hepatoma cells was dose-dependently reduced by sodium butyrate. Flow cytometric analysis showed cell-cycle arrest at the G1 phase in the sodium butyrate-treated cells. Apoptotic change was never found in treated cells at concentration levels of less than 5 mmol/L. Sodium butyrate decreased p53 expression and increased p21WAF-1 expression in HCC-T and HCC-M cells having the wild-type p53 gene. Western blot analysis showed that Bcl-2 was expressed in the HCC-T and HCC-M cells, and its expression was increased after exposure to sodium butyrate. Antisense oligodeoxynucleotide against bcl-2 easily caused apoptosis. These results indicate that sodium butyrate hardly induces apoptotic change in the human hepatoma cell lines, HCC-T and HCC-M, with the increase of Bcl-2 expression. Cell-cycle arrest in the G1 phase caused by sodium butyrate was suggested to be induced by the increase in p21WAF-1 expression, but this change did not link with the p53 increase.
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PMID:Loss of butyrate-induced apoptosis in human hepatoma cell lines HCC-M and HCC-T having substantial Bcl-2 expression. 958 76

In the development of a cancer, unlimited cell proliferation has been believed to play an important role. In addition, a programmed cell death called apoptosis, which is regulated by several oncogenes and tumor suppressor genes, has been suggested to be another important different pathway of carcinogenesis. Recently, several reports on cell proliferation capacity and apoptosis in the development of human liver disease have been published, but the cell proliferation index and its relationship between the expression of the bcl-2 and p53 genes involving apoptosis has not yet been discussed in view of the clinical differences of primary and metastatic liver cancer. In this study, we investigated the cell proliferation index and expression of p53 and bcl-2 in the tumorous and non-tumorous portions of both hepatocellular carcinoma and metastatic liver cancer. The expression of p53 was observed in both hepatocellular carcinoma and metastatic liver cancer, but bcl-2 expression was observed neither in hepatocellular carcinoma nor in metastatic liver cancer. In hepatocellular carcinoma, the p53 positive group showed a higher Ki-67 score (cell proliferation index) and more tumor numbers than the p53 negative group (p < 0.05). In metastatic liver cancer, the results were the same as in hepatocellular carcinoma (p < 0.05). However, we could not correlate the p53 expression and its prognostic significance in hepatocellular carcinoma.
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PMID:Cell proliferation index and the expression of p53 and Bcl-2 in tumorous and non-tumorous lesions of hepatocellular carcinoma and metastatic liver cancer. 982 91

Expression of the Bcl-2 family members in a human hepatocellular carcinoma cell line (HCC-T) after sodium butyrate-treatment was investigated. Sodium butyrate, a histone deacetylase inhibitor, induced differentiation of the cell line into its normal counterpart without inducing apoptosis at the concentration of 2 mmol/l. Since sodium butyrate has effects on both differentiation and apoptosis, we investigated the expression profile of bcl-2 related genes in HCC-T. The expression of Bcl-2 and Mcl-1/EAT was up-regulated 4-12 h after the treatment while Bcl-XL was up-regulated 2-3 days after the stimulation. On the other hand, the expression levels of Bax protein remained unchanged during differentiation. The HCC-T cells entered a cell cycle arrest at G1 and showed neither cellular fragmentation nor apoptosis during this period, which was concomitantly associated with up-regulated expression of a cell cycle regulator, p21WAF-1. These results demonstrate that induction of anti-apoptotic bcl-2 related proteins at an early stage of differentiation is important for the maintenance of HCC-T cell differentiation by antagonizing pro-apoptotic molecules such as Bax.
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PMID:Bcl-2 related proteins are dramatically induced at the early stage of differentiation in human liver cancer cells by a histone deacetylase inhibitor projecting an anti-apoptotic role during this period. 1067 72

Chemotherapy does not have a prominent role in the treatment of hepatoma. However, an acyclic retinoid prevented tumor recurrence post-hepatectomy, and tamoxifen (TAM) induced apoptosis in tumor cells. Combination therapy of these agents on proliferation and apoptosis of hepatoma cells has not been explored. HepG2, Hep1B, Hepa1-6 and MH1C1 hepatoma cells were incubated with TAM, 9-cis- and all-trans retinoic acid (CRA, ATRA, respectively) alone or in combination. Proliferation rate was assessed and apoptosis was analyzed by flow cytometry, immunostaining, caspase activity assays and the expression of apoptosis- and/or cell cycle-related molecules. CRA and TAM, but not ATRA monotherapy were moderately effective. Apoptosis was accompanied by upregulation of caspase 3 and 8 activity, and increased p27, bax, caspase 3 expression, while the levels of p21cip/waf and bcl-2 were unchanged or decreased. Combination therapy enhanced apoptosis from a maximum of 60% after monotherapy to more than 90% after 96 h in all cell types. Pro-apoptotic effects were paralleled by inhibition of proliferation. Combination of TAM and CRA, but not ATRA, have an additive to synergistic anti-proliferative and pro-apoptotic effect on HCC cells. This justifies trials for HCC using combinations of these biological response modifiers.
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PMID:Combined in vitro anti-tumoral action of tamoxifen and retinoic acid derivatives in hepatoma cells. 1174 47

We have isolated two stable human bcl-2 transfected cell lines, HCC-T-bcl and PLC-bcl, that were derived from the transfection of two human hepatocellular carcinoma cell lines (HCC-T and PLC/PRF/5, respectively) with a plasmid vector containing recombinant bcl-2 (pCAGGS-bcl).) Cell lines transfected with the plasmid alone (pCAGGS-neo) were also established as controls (HCC-T-neo and PLC-neo). HCC-T-neo and PLC-neo were sensitive to doxorubicin-induced apoptosis, as defined by morphological observation. Although HCC-T-neo expressed endogenous Bcl-2, the sensitivity of HCC-T-neo to doxorubicin-induced cytotoxicity was similar to that of PLC-neo, which does not express endogenous Bcl-2. In contrast, both HCC-T-bcl and PLC-bcl were more resistant to doxorubicin-induced cytotoxicity. Although these bcl-2 transfectants were resistant to the drug-induced apoptosis, Bcl-2 overexpression did not affect doxorubicin-induced growth suppression. These results suggest that the overexpression of Bcl-2 renders human HCC cells resistant to doxorubicin-induced cytotoxicity.
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PMID:Bcl-2 prevents doxorubicin-induced apoptosis of human liver cancer cells. 1264 56

The aim of this work was to study the effect of arsenic trioxide (As2O3) on rat hepatocellular carcinoma (HCC), and investgate on the mechanisms of its antitumor effect. HCC was induced by chemocarcinogen diethylnitrosamine (DEN) in Wistar rats, that were then treated with As2O3 intraperitoneally in three different concentrations once a day for two weeks, and twice a week for another two weeks. The histological and ultrastructural changes in liver tissue were observed under microscope and electronic microscope on the 7th, 14th and 28th day after drug administration. The apoptosis and cellular dynamic parameters of tumor cells were observed by flow cytometry. The expression of bcl-2, bax, and proliferation cell nuclear antigen (PCNA) of rat liver cancer cells on the 7th day after drug administration was determined by using immunohistochemical technique. Treatment with As2O3 caused HCC cells death via both apoptotic and non-apoptotic mechanisms when the dose was high (5 mg.kg(-1)), while necrosis was rare and apoptosis was common when the dose was appropriate (1 mg.kg(-1)). This effect was obviously accompanied with accumulation of cells in G2/M phases (G2/M restriction). Many apoptotic cells were also found in G2/M phases. The expression intensity of bcl-2 or bax varied depending on the dose administrated. Downregulation of bcl-2/bax was observed, accompanied with upregulation of apoptosis. However, the ratio of bcl-2/bax and the percentage of apoptosis were not the utmost when the dose administered was the highest. In conclusion, these data demonstrate that As2O3 induces apoptosis of rat HCC cells, and it is closely associated with G2/M restriction when apoptosis reaches the top. Apoptosis can be observed in all three phases of cell cycle, but it is more common in G2/M phase when the dose is appropriate. It is suggested that arsenic trioxide may be an atypical cell cycle specific agent. Apoptosis of tumor cells is closely associated with down-regulation of the ratio of bcl-2/bax, but that may not be the only dominant factor.
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PMID:Arsenic trioxide induces apoptosis of rat hepatocellular carcinoma cells in vivo. 1272 24

Sodium butyrate is a short-chain fatty acid produced by fermentation in the gastrointestinal tract. It induces differentiation of several kinds of cancer by inhibiting histone deacetylase activity. We have reported that butyrate stimulates hepatocellular carcinoma cells into their normal phenotype. Since sodium butyrate affects both differentiation and apoptosis, we investigated expression of bcl-2-related genes in a human hepatocellular carcinoma cell line HCC-T. The expression of anti-apoptotic Bcl-2 and Mcl-1/EAT was up-regulated 4 h after the treatment, while pro-apoptotic Bax expression did not change. Gene expressions in the early stage of butyrate-stimulation were investigated by the differential display assay and the cDNA expression array. Laminin and keratin 18 were increased 6 h after the stimulation with sodium butyrate. The results of cDNA expression array revealed up-regulation of cell cycle inhibitory genes such as cyclin-dependent kinase 4 inhibitor, and interferon-related genes such as STAT2 and 3, while down-regulation of cyclin-dependent kinase 2 and cyclin E. Up-regulated production of p21WAF-1 and Mcl-1/EAT was also confirmed by Western blotting. The cytoskeletal change indicated by up-regulation of laminin and keratin 18 may be an important factor in the decrease in malignant phenotype of cancer cells. Up-regulation of interferon-related genes indicated that butyrate-treatment might induce a similar phenotypic change to that induced by type 1 interferons. This study suggests several target genes for the future gene therapy of cancer or genes preventing cancer development from pre-malignant tissues.
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PMID:Gene expression associated with the decrease in malignant phenotype of human liver cancer cells following stimulation with a histone deacetylase inhibitor. 1558 45

The effect of targeted magnetic nanoparticles on hepatoma and the underlying mechanism were examined. Nude mice transplanted with a human hepatoma cell line (HepG2 cells) were randomized into 5 groups, including: (1) group A, receiving normal saline, (2) group B, receiving 5-fluorouracil (5-Fu), (3) group C, receiving magnetic nanoparticles containing 5-Fu, (4) group D, consisting of treatment with magnetic nanoparticles containing 5-Fu and inside magnetic field and (5) group E, receiving pure magnetic nanoparticles and inside magnetic field. Morphological features of transplanted tumors in mice in each group were observed under transmission electron microscope (TEM). The expression of bcl-2/bax protein was immunohistochemically detected by SABC method. The results showed that a large number of apoptotic tumor cells were found in group B and group D under TEM. The expression of bcl-2 protein was significantly decreased and the expression of bax protein increased significantly in both group B and D as compared with those in group A, C and E (P<0.01 for all). The decrease in bcl-2 and the increase in bax were more in group D as compared with group B (P<0.01). It is concluded that the targeted magnetic nanoparticles containing 5-Fu can improve the chemotherapeutic effect of 5-Fu by decreasing bcl-2 expression, increasing bax expression and inducing apoptosis of the liver cancer cells.
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PMID:The effect of targeted magnetic nanopaticles on hepatoma and the expression of bcl-2/bax protein. 1870 8


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