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)

Scirrhous hepatocellular carcinoma (SHCC) is a rare variation of HCC, for which characteristics of tumor cells and the fibrotic stroma have not been clarified in detail. The present study was therefore carried out to elucidate cytological features of tumor and stromal cells and components of the stromal extracellular matrix in 15 SHCC patients undergoing hepatectomy without preoperative transarterial embolization. Diagnosis was on the basis of a scirrhous histological pattern exceeding 50% of the tumor area. Expression of cytoplasmic and extracellular matrix proteins was compared among SHCC, HCC and intrahepatic cholangiocarcinoma (ICC) cases with immunohistochemical staining. The lesions could be histologically divided into radiating and sinusoidal types. Common stromal components of SHCC and ICC were collagen types I and III. There was no expression of laminin-5 in the stroma of SHCC, but it was present in almost all ICC cases. Tenascin-C expression was significantly lower in the SHCC cases and its distribution differed between SHCC and ICC. Matrix metalloproteinase-7 (MMP-7) expression was significantly higher in SHCC compared with HCC. Almost all stromal cells were alpha-smooth muscle actin-positive both in SHCC and ICC, whereas glial fibrillary acid protein (GFAP)-positive stromal cells were significantly more increased in ICC than in SHCC. SHCC clearly differed from HCC with respect to collagen types I, III and MMP-7 expression, and from ICC with regard to stromal components including laminin-5, tenascin-C and GFAP(+) stromal cells.
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PMID:Cellular and stromal characteristics in the scirrhous hepatocellular carcinoma: comparison with hepatocellular carcinomas and intrahepatic cholangiocarcinomas. 1627 Oct 85

An autopsy case of carcinosarcoma of the liver producing granulocyte-colony stimulating factor (G-CSF) is reported. The patient, a 74-year-old Japanese man, presented with multiple liver masses. His serum G-CSF was elevated to 286 pg/mL and a marked leukocytosis of 19 100/microL was observed. The patient had a rapidly aggravated clinical course and died 57 days after admission. Autopsy revealed a liver carcinosarcoma composed both of hepatocellular carcinoma (HCC) and sarcomatous elements immunoreactive with alpha-smooth muscle actin and desmin. Immunohistochemistry revealed positive staining of G-CSF in the cytoplasm of HCC, whereas none of the spindle cells was positively stained. Production of G-CSF was also confirmed by enzyme-linked immunosorbent assay, using the frozen tumor tissue taken at the autopsy. Similar to the majority of G-CSF-producing tumors in the literature, only the epithelial elements of the present case were immunopositive for G-CSF. Although a monoclonal origin of carcinosarcomas has generally been proposed, heterologous differentiation from a single clone might lead to the production of G-CSF only in the epithelial element in the present case. It is suggested that G-CSF was associated with the high-grade transformation of the epithelial elements, as well as the reported phenomenon of conventional HCC producing G-CSF.
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PMID:Carcinosarcoma of the liver producing granulocyte-colony stimulating factor. 1679 52

Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.
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PMID:Primary hepatic lymphoma with spindle cell components: a case report. 1698 39

In previous studies, we have demonstrated that RhoA/B-dependent signaling regulates TGFbeta-induced rapid actin reorganization in Swiss 3T3 fibroblasts. Here we report that TGFbeta regulates long-term actin remodeling by increasing the steady-state mRNA levels of the RhoB gene in mouse Swiss 3T3 fibroblasts and human hepatoma HepG2 cells. We show that this regulation is specific for the RhoB gene and is facilitated by enhanced activity of the RhoB promoter. Adenovirus-mediated gene transfer of Smad2 and Smad3 in Swiss 3T3 fibroblasts induced transcription of the endogenous RhoB gene but not the RhoA gene. Interestingly, in JEG-3 choriocarcinoma cells that lack endogenous Smad3, TGFbeta-induced transcriptional up-regulation of the RhoB gene was not observed, but it was restored by adenoviral Smad3 overexpression. In addition, Smad2 and Smad3 triggered activation of RhoA and RhoB GTPases and long-term actin reorganization in Swiss 3T3 fibroblasts. Finally, Smad3, and to a lesser extent Smad2, induced transcription of the alpha-smooth muscle actin (alpha-SMA) gene, and enhanced the incorporation of alpha-SMA into microfilaments in Swiss 3T3 fibroblasts. These data reveal a novel mechanism of cross-talk between the classical TGFbeta/Smad pathway and Rho GTPases, regulating the rapid and the long-term actin reorganization that may control the fibroblast-myofibroblast differentiation program.
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PMID:A novel mechanism of TGFbeta-induced actin reorganization mediated by Smad proteins and Rho GTPases. 1863 Nov 73

In human hepatocellular carcinoma (HCC), epithelial to mesenchymal transition (EMT) correlates with aggressiveness of tumors and poor survival. We employed a model of EMT based on immortalized p19(ARF) null hepatocytes (MIM), which display tumor growth upon expression of oncogenic Ras and undergo EMT through the synergism of Ras and transforming growth factor (TGF)-beta. Here, we show that the interleukin-related protein interleukin-like EMT inducer (ILEI), a novel EMT-, tumor- and metastasis-inducing protein, cooperates with oncogenic Ras to cause TGF-beta-independent EMT. Ras-transformed MIM hepatocytes overexpressing ILEI showed cytoplasmic E-cadherin, loss of ZO-1 and induction of alpha-smooth muscle actin as well as platelet-derived growth factor (PDGF)/PDGF-R isoforms. As shown by dominant-negative PDGF-R expression in these cells, ILEI-induced PDGF signaling was required for enhanced cell migration, nuclear accumulation of beta-catenin, nuclear pY-Stat3 and accelerated growth of lung metastases. In MIM hepatocytes expressing the Ras mutant V12-C40, ILEI collaborated with PI3K signaling resulting in tumor formation without EMT. Clinically, human HCC samples showed granular or cytoplasmic localization of ILEI correlating with well and poorly differentiated tumors, respectively. In conclusion, these data indicate that ILEI requires cooperation with oncogenic Ras to govern hepatocellular EMT through mechanisms involving PDGF-R/beta-catenin and PDGF-R/Stat3 signaling.
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PMID:ILEI requires oncogenic Ras for the epithelial to mesenchymal transition of hepatocytes and liver carcinoma progression. 1901 38

Toluene is one of the most widely used organic solvents and is commonly recognized as a noxious substance inducing chronically toxic damage to neural, hepatic and renal functions in the workers engaged in printing and painting. Although hepatic cells are generally considered to be vulnerable and susceptible to various organic solvents, particularly chloroform and other halogenated hydrocarbons, the hepatotoxic effects of aromatic hydrocarbons including toluene have not yet been sufficiently characterized. In particular, it still seems unclear whether toluene itself can directly act on hepatic cells, inducing toxic damage to their metabolism and function. To assess the toxic effect of toluene inhalation on rat liver, immunohistochemical analyses of the histological markers for hepatic damage were carried out in animals exposed subacutely to toluene vapor. The immunoreactivities of heat shock proteins (HSP-70 and HSP-90) and cytochrome P4502E1 (CYP2E1) in the liver were analyzed to assess the hepatotoxic damage induced by toluene inhalation, and the expression of these histological markers was shown to be substantially enhanced by the subacute exposure to toluene vapor. Toluene inhalation was furthermore shown to enhance the immunoreactivities of alpha-smooth muscle actin (alpha-SMA), collagen, glucocorticoid receptors (GR) and leptin receptors (Ob-R) in the liver. Additional studies using human hepatoma HepG2 cells showed that toluene can directly induce toxic damage to cells. These findings suggest that toluene inhalation may primarily induce hepatic damage, which may be secondarily exacerbated by the activation of systemic processes possibly connected with glucocorticoids and leptin.
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PMID:Immunohistochemical studies on early stage of hepatic damage induced by subacute inhalation of toluene vapor in rats. 1939 Nov 20

We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.
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PMID:Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies. 1943 76

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibited increases in the transforming growth factor-beta1 (TGF-beta1) mRNA and alpha-smooth muscle actin (alpha-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of alpha-SMA and TGF-beta1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of alpha-SMA and TGF-beta1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-beta1 expression via Nrf2/ARE activation.
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PMID:Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-beta1 expression. 1964 58

Obesity and related metabolic abnormalities, including insulin resistance, are risk factors for hepatocellular carcinoma in non-alcoholic steatohepatitis as well as in chronic viral hepatitis. Branched-chain amino acids (BCAA), which improve insulin resistance, inhibited obesity-related colon carcinogenesis in a rodent model, and also reduced the incidence of hepatocellular carcinoma in obese patients with liver cirrhosis. In the present study, we determined the effects of BCAA on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in obese C57BL/KsJ-db/db (db/db) mice with diabetes mellitus. Male db/db mice were given tap water containing 40 ppm DEN for an initial 2 weeks and thereafter they received a basal diet containing 3.0% of BCAA or casein, which served as a nitrogen content-matched control of BCAA, throughout the experiment. Supplementation with BCAA significantly reduced the total number of foci of cellular alteration, a premalignant lesion of the liver, and the expression of insulin-like growth factor (IGF)-1, IGF-2, and IGF-1 receptor in the liver when compared to the casein supplementation. BCAA supplementation for 34 weeks also significantly inhibited both the development of hepatocellular neoplasms and the proliferation of hepatocytes in comparison to the basal diet or casein-fed groups. Supplementation with BCAA improved liver steatosis and fibrosis and inhibited the expression of alpha-smooth muscle actin in the DEN-treated db/db mice. The serum levels of glucose and leptin decreased by dietary BCAA, whereas the value of the quantitative insulin sensitivity check index increased by this agent, indicating the improvement of insulin resistance and hyperleptinemia. In conclusion, oral BCAA supplementation improves insulin resistance and prevents the development of liver tumorigenesis in obese and diabetic mice.
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PMID:Dietary supplementation with branched-chain amino acids suppresses diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice. 1990 67

Activated hepatic stellate cells (HSC) are the primary source of extracellular matrix proteins found in liver fibrosis/cirrhosis patients. Therefore, the prevention of HSC activation is an important strategy for treating severe liver injury. This study examined the effects of KR62776, a new peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, on the rate of cell proliferation and expression of alpha-smooth muscle actin (alpha-SMA) in rat hepatic stellate HSC-T6 cells. In addition, its effects on the liver damage induced by carbon tetrachloride were investigated. KR62776 caused the apoptosis of activated HSC-T6 cells with the concomitant decrease in the alpha-smooth muscle actin levels in a time- and concentration-dependent manner. However, KR62776 did not cause the apoptosis of human HepG2 and rat McARH7777 hepatoma cells, suggesting that KR62776 has a specific effect on stellate cells. KR62776 increased the levels of Gadd45, p27, p21 and PPARgamma proteins but decreased the cell cyclerelated proteins, such as cdk2, cyclin B and cyclin D1. These changes were reversed by BADGE, a specific PPARgamma antagonist, indicating that the effects of KR62776 are, at least in part, PPARgamma-dependent. In addition, KR62776 administration showed some protection against carbon tetrachloride-induced hepatocellular damage in rats. Overall, these results suggest that KR62776 may have potential in the chemoprevention of liver fibrosis/cirrhosis.
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PMID:Selective inhibition of activated stellate cells and protection from carbon tetrachloride-induced liver injury in rats by a new PPARgamma agonist KR62776. 2036 9


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