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)

A previously healthy 22-year-old woman was admitted with a complaint of right upper quadrant abdominal pain for 2 weeks. Her past history was not remarkable. On admission, HBsAg and anti-HCV were negative and alpha-FP was within normal range. Abdominal sonography and CT showed a mass in liver measuring 10 x 11 cm with features of central necrosis and hemorrhage. On 6th hospital day, hemoperitoneum developed suddenly. She underwent emergency laparotomy and trisegmentectomy. Intraoperative finding revealed a hemoperitoneum with a tumor filled with liquefied necrotic tissues. Microscopically, the tumor was mostly composed of pleomorphic spindle cells with abundant anastomosing vascular channels and partly composed of tumor cells with trabecular arrangement. On immunohistochemical staining, tumor cells reacted with cytokeratin and vimentin, while CD34 and hepatocyte staining revealed negative. She died 2 months after the operation. We report a case of rapidly deteriorated primary sarcomatoid hepatocellular carcinoma in a young female without any risk factor.
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PMID:[A case of sarcomatoid hepatocellular carcinoma in a young female without risk factor]. 1680 54

Dendritic cells (DCs) are professional antigen presenting cells that are being considered as potential immunotherapeutic agents to promote host immune responses against tumor antigens. The use of such modified antigen-presenting cells for research or therapeutic have been limited by several factors, including maintaining DCs in a highly activated state, efficient transduction and expression, stable expression, identification of appropriate tumor-associated antigens, and absence of unintended functional changes or cytotoxicity. In this study, the feasibility of using CD34-DCs for tumor immunotherapy after transduction with a recombinant adenovirus containing HBsAg gene (AdVHBsAg), an HCC-associated antigen, was investigated. The gene transfer with recombinant adenovirus vectors (AdV) can obtained high levels of stable expression of HBsAg and its efficiency was increased in a multiplicity of infection (MOI)-dependent manner. Moreover, the AdVHBsAg infection had no appreciable effect on apoptosis of DCs compared with that of mock-infected DCs. The T cell lines, primed by the recombinant AdVHBsAg-infected DCs in vitro, recognized HBsAg-expressing tumor cell lines in a human leukocyte antigen (HLA) class I-restricted manner, and evoked a higher CTL response, which indicated that high potent and specific antitumor immune response could be induced by AdVHBsAg DC vaccine. It may be a promising the therapeutic modality for the treatment of HBsAg-expressing tumors, and will be a foundation for further study on DC vaccines and gene therapy for HCC.
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PMID:Dendritic cell generated from CD34+ hematopoietic progenitors can be transfected with adenovirus containing gene of HBsAg and induce antigen-specific cytotoxic T cell responses. 1687 81

Due to the development of the imaging techniques and liver surgery, pathologists are encountered more frequently with preneoplastic liver lesions. Well-defined stages of human hepatocarcinogenesis have been distinguished recently. Dysplastic foci represent the earliest stage of this process. Small-cell dysplastic foci are tumor precursors, but the large-cell form of this lesion does not progress further. The next stage is the dysplastic nodule, this larger lesion can be recognized by imaging techniques and gross examination of the specimen. Low- and high-risk forms are distinguished based on the level of cytological and structural atypia. The small hepatocellular carcinomas have a diameter of less than 2 cm by definition. The small HCC of indistinctly nodular type is equivalent of in situ carcinomas in other organs and designated sometimes as early HCC. The small HCC of the distinctly nodular type can be interpreted as advanced cancer despite its small size. The distinction between these lesions can be facilitated by ancillary techniques. The so-called capillarization of the liver sinusoids during the progression is characterized by the increased expression of endothelial markers as CD31 and CD34. Immunostaining for CD44, beta-catenin and p53 has prognostic value. Molecular biological techniques reveal gradual epigenetic and DNA changes during the process of hepatocarcinogenesis. Global gene expression profiling of hepatocellular carcinomas may result in a new classification of this tumor and can reveal new potential therapeutic targets.
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PMID:[Hepatocarcinogenesis in human liver]. 1688 73

Oncolytic adenovirus (rAd)-mediated E1A gene therapy of cancer has become a novel therapeutic modality. In this study, we constructed a recombinant oncolytic adenovirus (rAd-E1A) expressing the tumor suppressor E1A gene. We demonstrated that the rAd-E1A replicated in HepG2 and SMMC-7721 human hepatocellular carcinoma (HCC) cells but attenuated in the normal liver cell line HL-7702. It induced HCC cell apoptosis through upregulation of apoptosis-associated Bax, caspase-3, and Fas and downregulation of survivin and Bcl-2 in a p53-dependent pathway. It also downregulated the expression of angiogenesis- associated vascular endothelial growth factor (VEGF) and CD34 genes and reduced tumor vessel formation and angiogenesis. In mice bearing SMMC-7721 tumors, intratumoral injections of rAd- E1A significantly inhibited HCC growth. Therefore, the oncolytic adenovirus-mediated E1A gene therapy may be a useful therapeutic approach for HCC treatment.
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PMID:Oncolytic adenovirus-mediated E1A gene therapy induces tumor-cell apoptosis and reduces tumor angiogenesis leading to inhibition of hepatocellular carcinoma growth in animal model. 1691 99

Hepatocellular carcinoma (HCC) is known for its histomorphologic heterogeneity. Immunohistochemistry (IHC) can help in the comparative morphologic evaluation of HCC, its variants and their mimics. Some of these diagnostic challenges can be attributed to (i) the variety of neoplasms that can arise from the hepatic stem cell lineage; (ii) the spectrum of well-differentiated hepatocellular nodular lesions; (iii) the liver being a target for metastases with some of these histologic entities mimicking variants of HCC or actually arising in the liver; and (iv) the limitations of serum alpha-fetoprotein (AFP). The role of IHC is in the distinction of benign hepatocellular nodules from reactive hepatocytes; WD-HCC from benign hepatocellular nodules; poorly differentiated HCC from cholangiocarcinoma and metastases; and determination of histogenesis of malignant tumor; and of primary site of origin of malignant tumor. A panel of antibodies has more discriminant value. AFP expression usually indicates malignancy in a hepatocellular nodule and hepatocytic histogenesis of a malignancy. Polyclonal carcinoembryonic antigen (pCEA) and CD10 stain bile canaliculi in better-differentiated HCC. HepPar1 is generally accepted as a hepatocytic marker. However, not all HCC stain uniformly and not all HepPar1-positive tumors are of hepatocytic origin or arise in the liver. Mature hepatocytes and hepatocellular nodules stain with CAM 5.2, CK 8, and 18 but not with CK 7, 19, 20, or AE1/AE3. Biliary epithelium expresses CK 7 and 19. CD 34 highlights sinusoidal capillarization. AFP, pCEA/CD10, and CD34 are useful for ascertainment of malignancy in hepatocellular nodules; HepPar1 and cytokeratins to be included if histogenesis is the issue. IHC results should be interpreted in the larger context of the case.
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PMID:Diagnostic utility of immunohistochemistry in hepatocellular carcinoma, its variants and their mimics. 1693 16

This study evaluated the significance of circulating bone marrow-derived endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were recruited for the study, and 16 patients with liver cirrhosis and 14 healthy subjects were also included for comparison. Blood samples were taken before treatment. Total mononuclear cells were isolated from peripheral blood, preplated to eliminate mature circulating endothelial cells, and colony-forming units (CFUs) formed by circulating EPCs were counted. To validate the CFU scores, FACS quantification of EPCs using CD133, VEGFR2, and CD34 as markers was performed in 30 cases. Our study showed significantly higher mean CFU scores in patients with HCC compared to patients with cirrhosis and healthy controls (P = .001 and .009, respectively). Furthermore, the CFU scores of patients with HCC positively correlated with levels of serum alpha-fetoprotein (r = .303, P = .017), plasma VEGF (r = .242, P = .035), and plasma interleukin-8 (IL-8) (r = .258, P = .025). Patients with unresectable HCC had higher CFU scores than patients with resectable tumors (P = .027). Furthermore, for those who underwent curative surgery, higher preoperative CFU scores were observed in patients with recurrence within 1 year compared with those who were disease-free after 1 year (P = .013). In conclusion, higher circulating levels of EPCs are seen in patients with advanced unresectable HCC as compared to patients with resectable HCC or those with liver cirrhosis. Our evidence supports the potential use of circulating level of EPCs as a prognostic marker in patients with HCC.
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PMID:Significance of circulating endothelial progenitor cells in hepatocellular carcinoma. 1700 19

Both Secreted Protein Acidic and Rich in Cysteine (SPARC) and Hevin are multifunctional matricellular glycoproteins. Recent experimental studies suggested that Hevin and SPARC together diminish angiogenesis, but their significance in hepatocellular carcinoma (HCC) remains unclear. This study aimed to correlate SPARC and Hevin expression with angiogenesis and clinicopathological features in HCC. SPARC and Hevin protein and mRNA expression in HCC specimens were assessed by immunostaining, immunoblotting, and quantitative reverse transcriptase-polymerase chain reaction. Tumour microvessel density (MVD) was assessed by CD34 immunostaining. The role of SPARC and Hevin in HCC was further assessed in an in vivo nude mice xenograft model. Both SPARC and Hevin mRNA levels were significantly higher in tumours than in non-tumourous livers. A significant correlation between tumour SPARC and Hevin mRNA levels was found. Moreover, SPARC protein localized in the tumour sinusoidal area correlated significantly with Hevin protein localized in HCC cells. Truncated forms of SPARC and Hevin proteins were detected in clinical samples. Truncated SPARC protein localized in the tumour sinusoidal area correlated significantly with tumour MVD. On the other hand, overexpression of full-length SPARC in tumour xenografts in athymic nude mice significantly delayed tumour growth, and this delay was related to a decrease in tumour angiogenesis. Expression of Hevin protein within HCC cells was related to the presence of tumour encapsulation and the absence of hepatitis B surface antigen in clinical samples. Overexpression of Hevin in tumour xenografts also significantly delayed tumour growth. In conclusion, this study has shown that SPARC and Hevin are upregulated in HCC compared with non-tumourous liver, and that they are inter-related at both mRNA and protein levels. Moreover, both SPARC and Hevin were related to HCC angiogenesis and tumour progression.
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PMID:SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma. 1702 19

The human interleukin-17F(hIL-17F) gene was amplified by RT-PCR from PHA-activated human peripheral blood mononuclear cells (PBMCs). It was then subcloned into the retrovirus vector pSIV-1. The pSIV-1/hIL-17F together with its two-helper virus vectors pHIT456 and pHIT60 cotransfected into the package cell 293T by lipofectin to produce mature recombinant retrovirus, which was then used to infect SMMC-7721 hepatocarcinoma cells (HCCs), and the cells were selected in the presence of G418. The integration, transcription, expression of hIL-17F gene in SMMC-7721 cells was identified by PCR, RT-PCR and Western blot respectively. MTT and FCM showed that hIL-17F couldn't alter the proliferation and cell cycle of SMMC-7721 cells, but ELISA showed that it could down-regulate IL-6, IL-8 and VEGF expression. The effect of rhIL-17F supernatant on growth suppressing of ECV304 cells was observed by MTT. The experiment of human hepatocarcinoma xenograft tumor in nude mice showed that the formation and growth rates of hIL-17F-transgenic SMMC-7721 showed an obvious decline, and VEGF and CD34 expression and angiogenesis of the transgenic neoplasms was also evidently defined. hIL-17F can markedly inhibit the growth of human hepatocarcinoma xenograft tumor in nude mice by antiangiogenesis. This study provided an experimental evidence for further conducting tumor gene therapy by targeting vascularity and exploiting antiangiogenic novel medicine related to hIL-17F.
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PMID:[The effect of human IL-17F on growth of human hepatocarcinoma xenograft tumor in nude mice]. 1703

The aim of the present study was to detect the correlation between the expression of vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang2), ephrinB2 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and carcinogenesis or portal vein tumor thrombus (PVTT) formation in human hepatocellular carcinoma (HCC). The expression of VEGF, Ang2, ephrinB2 and EG-VEGF was detected by RT-PCR in 54 cases HCC without PVTT (group A), 9 cases HCC with PVTT (group B), 10 normal liver tissues (group D) and 10 cirrhosis tissues (group C). The samples were also stained with CD34 by immunohistochemistry. Quantitation of microvessel density (MVD) and semi-quantitation of VEGF, Ang2, ephrinB2 and EG-VEGF expression were analyzed to find the relations. The MVD was 146.69 +/- 77.79, 214.07 +/- 54.41, 32.85 +/- 8.49 and 34.83 +/- 8.29 in group A-D respectively with significant difference (F = 19.77, P = 0.000). The MVD in group A was higher than that in group C P = 0.006, but lower than that in group B P < or = 0.05 or 0.01. The expression levels of VEGF165, VEGF189, Ang2 and EG-VEGF mRNA were significantly different among the groups. The expression levels of VEGF165, Ang2 and EG-VEGF mRNA in group A were all higher than those in group C, but lower than those in group B P < 0.05 or 0.01. The MVD was significantly correlated with VEGF165, VEGF189, Ang2 and EG-VEGF mRNA with Spearman's related coefficient being 0.764, 0.510, 0.640 and 0.366 in HCC (P = 0.000, 0.000 0.000 and 0.003). In conclusion VEGF, Ang2 and EG-VEGF mRNA may play a role in angiogenesis and carcinogenesis of HCC. They can promote PVTT formation in HCC by modulating angiogenesis.
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PMID:Correlation of four vascular specific growth factors with carcinogenesis and portal vein tumor thrombus formation in human hepatocellular carcinoma. 1716 81

Few studies about angiogenesis in hepatocellular carcinoma (HCC) have been conducted and little is known about the significance of angiogenesis in HCC. In this study, the clinicopathological significance of tumor microvessel density (MVD) was assessed in 105 patients with HCC by immunohistochemical staining of CD105, CD34, and vascular endothelial growth factor (VEGF). Moreover, the use of the tissue microarray technique in evaluating angiogenesis of HCC was appraised. The MVD by CD105 immunostaining (MVD-CD105) was significantly lower in larger tumors (5 cm diameter as a cutoff point, p=0.001), more aggressive tumors, as indicated by venous infiltration (present vs absent, p=0.001), and tumors with advanced TNM stage (stage I & II vs stage III, p=0.011). A lower score of MVD by CD34 immunostaining (MVD-CD34) showed significant association only with venous invasion (p<0.001), whereas the MVD by CD105 immunostaining in tissue microarray (MVD-MA) was significantly lower only in larger sized tumors (p=0.043). Moreover, MVD-CD105 was positively associated with the expression intensity of VEGF (p=0.009), but not for MVD-CD34 (p=0.088). When median scores of MVD were used as cut-off points, the patients with higher score of MVD-CD105 had a significantly poorer prognosis in either disease-free or overall survival analysis (p=0.002 and p=0.009, respectively), whereas similar prognostic significance of MVD-CD34 was not observed in overall survival analysis (p=0.052) but was observed in disease-free survival analysis (p=0.022). No prognostic significance of MVD-MA was found in either disease-free or overall survival analysis (p=0.277 and p=0.712, respectively). These data demonstrate the superiority of CD105 over CD34 as a marker of angiogenesis in HCC and indicate that the tissue microarray technique is unsuitable for evaluating angiogenesis in HCC.
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PMID:Endoglin (CD105) expression in angiogenesis of primary hepatocellular carcinomas: analysis using tissue microarrays and comparisons with CD34 and VEGF. 1731 68


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