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)

Fetal rat hepatocytes treated with transforming growth factor beta (TGF-beta) die by apoptosis. However, a subpopulation of them survives and undergoes an epithelial mesenchymal transition (EMT). This transition also occurs upon incubation with fetal bovine serum. We have isolated the subpopulations that undergo EMT (TGF-beta-treated-fetal hepatocytes: TbetaT-FH; serum-treated-fetal hepatocytes: ST-FH) and show that they present high levels of vimentin and Snail expression and lack cytokeratin 18 and E-cadherin. Both TbetaT-FH and ST-FH cells require mitogens to grow and maintain the response to TGF-beta in terms of growth inhibition. However, they lack differentiation markers such as the liver-enriched transcription factors hepatocyte nuclear factor 4 (HNF-4) or HNF-1alpha and express the progenitor marker OV-6. Interestingly, the EMT process confers them resistance to the apoptotic effect of TGF-beta, with cells showing higher levels of active AKT and Bcl-x(L) than fetal hepatocytes. In summary, these cells are refractory to the apoptotic effects of TGF-beta, showing characteristics of liver progenitors and of some hepatocellular carcinoma cells.
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PMID:The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor Beta in fetal rat hepatocytes. 1249 70

A mixed epithelial tumour in the liver of a 24-month-old male Wistar rat from a 30-month inhalation study is described. The rat, which was in a group exposed to low concentrations of diesel exhaust, was euthanized because of emaciation, forced respiration and abnormal gait. Macroscopic examination of the enlarged liver revealed multiple partly confluent beige-red nodules up to 1.5 cm in diameter. Small nodules up to 7 mm in diameter were seen in the spleen. Histologically, the tumour nodules in the liver consisted of hepatocellular and cholangiocellular components. The hepatocellular component consisted of moderately differentiated polygonal to round hepatocytes about twice as large as normal hepatocytes and having hyperchromatic, centrally located nuclei with prominent nucleoli and eosinophilic cytoplasm. Foci of haematopoiesis and focal necroses were prominent. The cholangiocellular component was moderately differentiated and consisted of tubular structures lined by low cuboidal to cylindrical cells showing cytoplasmic basophilia and small dark nuclei without prominent nucleoli. The histological features of the nodules in the spleen corresponded to those of the primary tumour in the liver. Based on these criteria, the tumour nodules were diagnosed as hepatocholangiocellular carcinoma. The immunohistological examination confirmed the diagnosis, i.e. immunostaining for cytokeratins was positive for eight and 18 (hepatocellular carcinoma) and for seven and 19 (cholangiocellular carcinoma) as well as for vimentin (dense fibrous stroma). This tumour is considered to be spontaneous because of its single occurrence.
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PMID:Hepatocholangiocellular carcinoma in a rat--case report. 1254 36

We report a case involving well-differentiated hepatocellular carcinoma (HCC) developing to HCC with sarcomatous changes after radiofrequency ablation (RFA). In a cirrhotic patient with both hepatitis B surface antigen and hepatitis C virus RNA, a well-differentiated HCC with a diameter of 2 cm was detected in segment IV of the liver. A combination of transcatheter arterial embolization and percutaneous ethanol injection (PEI) was performed and, after 8 months, PEI was performed for recurrent tumors. Fifteen months after the first treatment, a recurrent tumor measuring 3.5 cm in diameter was detected in segment IV, which was demonstrated as well-differentiated HCC by tumor biopsy, and treated by RFA. Although the treated lesion was reduced to 2.5 cm in diameter 6 months after RFA, the tumor rapidly enlarged to 6 cm in diameter 2 months later and progressed to lymph node metastasis. Aspiration biopsy showed spindle-shaped sarcomatoid cells with positive staining for both vimentin and keratin. The patient died of HCC progression 10 months after RFA. Autopsy findings showed both sarcomatoid cells and trabecular HCC cells. The sarcomatoid cells had metastasized to the lymph nodes and distant organs. This is the first case illustrating a sarcomatous HCC after RFA. Of interest, RFA may be related to the development of sarcomatous HCC.
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PMID:Hepatocellular carcinoma with sarcomatous change arising after radiofrequency ablation for well-differentiated hepatocellular carcinoma. 1456 32

Vimentin is a growth-related gene and often expressed when epithelial cells are stimulated to proliferate by growth factors. In cancer, vimentin expression is associated with a dedifferentiated malignant phenotype, increased motility, invasive ability and poor prognosis. We studied the regulation of vimentin mRNA and multistep invasion processes following treatment of 12-O-tetradecanoylphorbol 13-acetate (TPA) and all-trans-retinoic acid (RA) in Hep 3B hepatocellular carcinoma cells. TPA showed marked induction of vimentin mRNA, while RA decreased the mRNA level. TPA or RA did not affect cell proliferation, cell-matrix protein adhesion, and matrix metalloproteinases and urokinase plasminogen activator activities. In vitro invasion ability was significantly increased or decreased with TPA or RA treatment, paralleled to the in vitro motile activity, respectively. These findings suggest that TPA and RA could modulate the invasive potential of Hep 3B cells by altering cellular motility related to differential regulation of vimentin mRNA.
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PMID:Differential regulation of vimentin mRNA by 12-O-tetradecanoylphorbol 13-acetate and all-trans-retinoic acid correlates with motility of Hep 3B human hepatocellular carcinoma cells. 1467 Jun 23

Cholangiocarcinoma (CCA), a malignant tumor derived from bile duct epithelium, occurs with a higher incidence in tropical countries, such as Thailand. Distinguishing CCA from hepatocellular carcinoma (HCC) of the liver often requires the use of histochemistry, so molecular markers for diagnosis and prognosis are still required. In this study, the two-dimensional (2-D) protein map of a Thai human bile duct epithelial carcinoma cell line (HuCCA-1) has been compared to human hepatocellular carcinoma cell lines (HepG2 and HCC-S102) and a human breast epithelial cancer cell line (MCF-7). Our results show that HuCCA-1 expressed a unique pattern of proteins. Forty-three major proteins were identified by matching to the map of MCF-7, and by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electrospray ionization-tandem MS (ESI-MS/MS). Cytokeratins CK8 and CK18 were overexpressed in both HuCCA-1 and HCC, while CK7 and CK19 were only expressed in HuCCA-1. Four specific proteins with MW/pI 57.2/5.21 (U1, vimentin), 42.2/6.20 (U2), 43.2/6.20 (U3, EF-TU), and 42.2/6.40 (U4, unidentified) were absent from HepG2. U2 showed high expression in HuCCA-1, while U1 and U4 showed high expression in HCC-S102. U2 could be separated in 2 proteins, U2/1 (alpha-enolase) and U2/2 (not identified) by using IPG pH 4-7. Galectin-3 showed high expression level in HuCCA-1 by 1-DE immunodetection, and gave only one spot with MW 32.9 kDa and pI 8.29 on 2-DE immunoblotting, Thus, certain proteins, namely CK7, CK19, U2/2 and galectin-3, may be good markers useful for differential diagnosis of cholangiocarcinoma compared to hepatocellular carcinoma.
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PMID:Proteomic analysis of cholangiocarcinoma cell line. 1504 94

Hepatitis C virus (HCV) is a causative agent of chronic hepatitis and hepatocellular carcinoma. The core protein of HCV packages the viral RNA genome to form a nucleocapsid. In addition to its function as a structural protein, core protein is involved in regulation of cellular transcription, virus-induced transformation, and pathogenesis. To gain insights into cellular functions of the core protein by identification of cellular proteins interacting with the core protein, we employed a proteomic approach. Hepatocytes soluble cytoplasmic proteins were applied to the core proteins immobilized on Ni-nitrilotriacetic resin and total bound cellular proteins were resolved by 2-DE. Analyses of interacting proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry allowed identification of 14 cellular proteins binding to the core protein. These proteins include DEAD-box polypeptide 5, similar in function to a known protein identified previously by yeast two-hybrid screening and 13 newly identified cellular proteins. Interestingly, nine protein spots were identified as intermediate microfilament proteins, including cytokeratins (five spots for cytokeratin 8, two for cytokeratin 19, and one for cytokeratin 18) and vimentin. Cytokeratin 8 and vimentin, which were previously shown to be involved in the infection processes of other viruses, were further analyzed to confirm their in vivo interactions with the core protein by immunoblotting and immunofluorescence microscopy. We discuss the functional implications of the interactions of the core protein with newly identified cellular proteins in HCV infection and pathogenesis.
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PMID:Proteomic profiling of cellular proteins interacting with the hepatitis C virus core protein. 1584 44

No more than 11 cases of carcinosarcoma of the liver have been reported in the past 40 years that fulfill the definition of hepatocellular carcinoma combined with differentiated sarcomatous elements. Most cases consist of hepatocellular carcinoma with 1 to 2 heterologous elements. We report a case of a 51-year-old woman with liver carcinosarcoma consisting of 3 carcinomatous components and 4 sarcomatous components. Hepatocellular carcinoma, fibrolamellar type, was accompanied by neuroendocrine carcinoma (neuron-specific enolase and synaptophysin positive) and adenocarcinoma (cytokeratin 7 and 20 positive). The sarcomatous elements consisted of poorly differentiated spindle cell neoplasm (vimentin positive), leiomyosarcoma (smooth muscle actin positive), rhabdomyosarcoma (desmin positive), and osteosarcoma. To our knowledge, this is the first case of liver carcinosarcoma with this many differentiated heterologous features. There are differing views on the pathogenesis of this tumor. Findings in this case support the view that metaplasia of carcinomatous cells gives rise to the sarcomatous elements.
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PMID:Carcinosarcoma of the liver: a case report and review of the literature. 1591 31

Reported herein is a case of hepatocellular carcinoma (HCC) with unusual peritoneal dissemination masquerading as peritoneal mesothelioma. A 61-year-old man was clinically found to have multiple tumors in his abdominal cavity; peritonitis carcinomatosa was suspected. An autopsy revealed numerous tumors of various sizes in the abdominal serosa, omentum, and diaphragm. No signs of tumor, fibrosis, or cirrhosis were found in the liver, except for a small nodule in the hepatic triangular ligament. Histologically, the tumor cells proliferated in thick trabeculae or in sheets and formed a few canaliculi and tubules with homogenously brown contents in their lumina, which stained positively with Hall stain. Immunohistochemically, these tumors were positive for hepatocyte, alpha-fetoprotein (AFP) and low-molecular-weight cytokeratin; were focally positive for pan-cytokeratin and epithelial membrane antigen (EMA); and were negative for high-molecular-weight cytokeratin, vimentin, and calretinin. Carcinoembryonic antigen (CEA) produced a bile canalicular immunohistochemical staining pattern. Thus, the tumor was diagnosed as an HCC (Edmondson II type) of the triangular ligament with massive peritoneal dissemination. The origin of this tumor and its differential diagnosis (malignant mesothelioma, hepatoid adenocarcinoma, and hepatoid yolk sac tumor) are discussed.
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PMID:Hepatocellular carcinoma with mesothelioma-like dissemination. 1627 Oct 87

The differential diagnoses of hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and adrenocortical carcinoma (ACC) are sometimes difficult due to their overlapping histologic features. Immunohistochemistry is a helpful adjunct in supporting the histologic diagnosis. In this study, the authors used the tissue array technique to systemically analyze the efficacy of different immunohistochemical panels in discerning these neoplasms. Immunohistochemical stains were performed on a total of 895 tumors (including 170 HCCs, 176 RCCs, and 40 ACCs) using monoclonal antibodies against hepatocyte antigen (HPA), CD10, RCC marker, vimentin, alpha-inhibin, keratins (KL-1, CAM 5.2, 7, and 20), epithelial membrane antigen, and polyclonal antibodies against carcinoembryonic antigen (pCEA) and alpha-fetoprotein, and antibodies Melan-A (A103), MOC31, and BG8. HPA immunostain alone detected 85.9% of HCCs, and the addition of canalicular pattern of pCEA and CD10 immunostains raised the sensitivity to 94.7%. RCC marker was positive in 54.5% of RCCs but was negative in all non-RCC tumors. Using positive CD10 and negative HPA and pCEA together with RCC marker increased the sensitivity to 74.4%. Immunoreactivity for alpha-inhibin and A103 could be detected in 67.5% and 55% of ACCs, respectively. When the two antibodies were combined, 82.5% of ACCs were labeled. Proper selection of immunohistochemical stains aid in the differential diagnosis of the three neoplasms. Using the tissue array technique, the authors also showed an effective model for comprehensive antibody testing.
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PMID:Differential immunoprofiles of hepatocellular carcinoma, renal cell carcinoma, and adrenocortical carcinoma: a systemic immunohistochemical survey using tissue array technique. 1628 Jun 64

Malignant gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors originating from the wall of the gastrointestinal tract. Their coexistence with other tumors originating from other germ layers is unique. We have reported a case of a 63-year-old GIST patient presenting as an epigastric mass associated with hepatic tumor. Histologically, the mesenteric tumor was composed of spindle cells showing both neural and smooth muscle differentiation. Immunohistochemical examination showed positive staining for CD117, vimentin, S-100, and SMA, while CD34 antigen was negative. The hepatic tumor was diagnosed as hepatocellular carcinoma (HCC). To the best of our knowledge, this is the first case of GIST and HCC coexistence. The rarity of the case, however, should not lead to ignoring such a possibility in differential diagnosis.
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PMID:Coexistence of hepatocellular carcinoma and gastrointestinal stromal tumor: a case report. 1648 90


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