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)

The aim of this study is to investigate whether the expression of CD147 could be a prognostic factor for hepatocellular carcinoma. Tissue samples from 111 hepatocellular carcinoma patients were immunohistochemically stained with anti-CD147, anti-matrix metalloproteinases-2 and anti-vascular endothelial growth factor antibodies. Tumor microvessel density was evaluated using CD34. The survival curves were estimated by Kaplan-Meier analysis and the prognostic significance of the marker was analyzed using the log-rank test. In addition, the identification of relevant prognostic factors was performed by multivariate Cox regression analysis. CD147 was mainly expressed in cancerous lesions and its expression was positively correlated with metalloproteinases-2 (P<0.0001), vascular endothelial growth factor (P<0.0001) and microvessel density CD34 (P<0.0001). Furthermore, CD147 was significantly associated with the presence of venous invasion (P=0.0013), tumor size (P<0.0001) and pTNM tumor stages (P=0.0001), as well as serum alpha-fetoprotein level (P<0.0001). Patients with positive expression of CD147 had poorer tumor recurrence-free survival than those with negative expression of CD147 (P<0.0001). Analyzed by a proportional hazard model, strong expression of CD147 had the highest risk ratio of recurrence among these markers (P<0.0001). The findings suggest that CD147 may be a significant independent predictor of poor survival in patients with hepatocellular carcinoma, and may be involved in tumor growth, invasion and angiogenesis in hepatocellular carcinoma.
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PMID:Expression of CD147 as a significantly unfavorable prognostic factor in hepatocellular carcinoma. 1741 90

Previous studies have shown that interleukin (IL)-24 as a novel tumor suppressor gene has tumor-suppressor activity in a broad spectrum of human cancer cells both in vitro and in vivo. In this study, we explored the potential effect of adenovirus-mediated IL-24 gene therapy on human hepatocellular carcinoma (HCC) by using a HCC cell line, SMMC-7721. We constructed a recombinant adenovirus, AdVGFP/IL-24 expressing the marker green fluorescent protein (GFP) and the tumor-suppressor gene, IL-24. We demonstrated that AdVGFP/IL-24 treatment of SMMC-7721 cells in vitro significantly induced HCC cell cytotoxicity and apoptosis, and altered HCC cell cycling with an S-phase reduction and G2/M phase arrest, compared with AdVGFP, without IL-24 expresssion (p < 0.05). Furthermore, we also showed that the treatment of SMMC-7721 tumors by an intratumoral injection of AdVGFP/IL-24 significantly suppressed in vivo HCC growth in athymic nude mice, compared with AdVGFP treatment (p < 0.05). In addition, we also elucidated the molecular mechanism responsible for AdVGFP/IL-24-associated tumor suppression. These include: (1) upregulation of p53-independent apoptosis-associated caspase-3 and (2) downregulation of angiogenesis-associated vascular endothelial growth factor and CD34. Therefore, this study will provide a framework for future clinical applications of AdVGFP/IL-24 in HCC gene therapy.
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PMID:Adenovirus-mediated Il-24 expression suppresses hepatocellular carcinoma growth via induction of cell apoptosis and cycling arrest and reduction of angiogenesis. 1762 14

Dysplastic nodules (DNs) are regarded as a premalignant lesion of hepatocellular carcinoma (HCC). Sinusoidal capillarization and unpaired arteries are reported in HCC and also to a lesser degree in DN. However, the mechanism and significance of these vascular alterations remain unclear. In this study, these vascular changes were examined with respect to vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1), hypoxia inducible factor-1alpha (HIF-1alpha), and CD34, by using 20 surgically resected cases of DNs and 36 cases of conventional HCC. The expression of these molecules was examined immunohistochemically. Although sinusoidal capillarization characterized by CD34 expression was found diffusely in HCC, such changes were found mainly in the areas around the portal tracts and also in other areas in DNs (focal in 6 cases, zonal in 7 cases, and extensive distribution in 7 cases). These capillarized areas were frequently associated with unpaired arteries, and the infiltration of neoplastic hepatocytes into the portal tracts and loss of reticulin fibers in DNs, particularly those with a zonal and extensive distribution. VEGF was diffusely expressed in neoplastic hepatocytes of DNs and HCC. Interestingly, Flk-1 and HIF-1alpha were mostly expressed in endothelial cells and neoplastic hepatocytes in the capillarized areas around portal tracts in DNs, respectively. In conclusion, the capillarized areas with increased numbers of unpaired arteries in DNs may represent an early malignant transformation. Increased expression of Flk-1 and HIF-1alpha associated with VEGF may be involved in sinusoidal capillarization and the increased numbers of unpaired arteries in these areas.
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PMID:Vascular endothelial growth factor, its receptor Flk-1, and hypoxia inducible factor-1alpha are involved in malignant transformation in dysplastic nodules of the liver. 1764 Jul 15

Hepatocellular carcinoma (HCC) may present in various ways, but only very rarely with symptoms of distant metastases or evolve from ectopic liver tissue. This report describes a case of a 62-year-old white man who was admitted for hemoptysis and a large left chest wall mass that was growing for about a year. The patient underwent Fine-needle aspiration (FNA) of the mass that revealed poorly differentiated large-cell carcinoma. A lung primary was suspected initially; however, further workup of this patient showed an elevated serum alpha-fetoprotein (AFP) level of 16,425 ng/ml. A computerized tomography (CT) scan of the abdomen showed cirrhotic liver, evidence of esophageal varices, but no evidence of a liver mass. The FNA findings were reviewed and ancillary studies were performed, including pan cytokeratin (AE1/3), Hepatocyte Paraffin 1 (HepPar-1), AFP, CD10, CD34, and polyclonal CEA. The results confirmed the diagnoses of HCC probably from occult primary or from ectopic liver tissue. The former was suggested, since serum AFP was dropped to 6,640 ng/ml following resection of the tumor. We concluded that HCC should be considered in the list of differential diagnosis of chest wall mass. HCC may present as metastatic disease from a clinically and radiologically unrecognized liver mass. FNA, coupled with ancillary studies, provides a rapid and accurate diagnostic tool in challenging cases.
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PMID:Cytomorphology of a solitary left chest wall mass: an unusual presentation from unknown primary hepatocellular carcinoma. 1770 51

P-glycoprotein (P-gp), which is encoded by the multidrug resistance gene (MDR-1); alpha fetoprotein (AFP); and vascular endothelium-associated antigens are well-known markers for human and canine hepatic diseases. We obtained liver tissues from 5 dogs with hepatocellular carcinoma (HCC) and 12 dogs with cirrhosis, and we performed histopathologic and immunohistochemical evaluations using anti-P-gp, anti-AFP, anti-CD31, and anti-CD34 antibodies. P-gp was expressed at higher levels in HCC than in cirrhotic livers ( P < .01), and was most commonly localized in biliary canaliculi and small ductuli. AFP was localized mainly in the cytoplasm in HCC ( P < .01) and in a few cases of cirrhosis. In both HCC and cirrhosis, the AFP-positive cells were morphologically similar to normal hepatocytes and showed an even cytoplasmic distribution of AFP. The endothelial markers CD31 and CD34 were used to investigate vascular distribution. CD31 was expressed strongly in the portal area and parenchyma in HCC, but it was rarely observed in the parenchyma in cirrhosis. CD34 expression could not be detected in both HCC and cirrhosis. This study constitutes the first comprehensive study of P-gp, AFP, and endothelial markers in canine HCC and cirrhosis. The importance of these markers in HCC and cirrhosis in dogs was demonstrated and provides a more accurate basis for a definitive diagnosis of HCC and cirrhosis in dogs.
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PMID:Cellular characterization of multidrug resistance P-glycoprotein, alpha fetoprotein, and neovascular endothelium-associated antigens in canine hepatocellular carcinoma and cirrhotic liver. 1784 32

The multistep process of hepatic carcinogenesis is mirrored by the morphologic classification of lesions detectable in cirrhosis, which include large regenerative nodules (LRN), low grade dysplastic nodules (LGDN), and high grade dysplastic nodules (HGDN). The latter belong to the "bordeline malignancy" category requiring accurate distinction from well-differentiated and early hepatocellular carcinoma (HCC). Nodules in cirrhosis are usually detected by non-invasive imaging techniques, which are unable to discriminate malignant from non-malignant forms, particularly in the 1-2-cm sized group. Liver biopsy is essential in providing practical diagnostic information to hepathologists in the management of cirrhotic patients with ultrasound (US)-detectable nodules. Histologic diagnosis on liver samples is based on the accurate search of a set of cyto-architectural features (e.g. cell atypia, cell crowding, trabecular thickness, microacini) and by a supplement of histochemical (Gomori staining) and immunocytochemical stainings. The latter rely upon the search of both well established and novel markers, targeted to evaluate stromal invasion (CK7/19), the vascular pattern (ASMA and CD34), or tumor markers (including HSP70 and glipican-3). Still, the diagnostic sensitivity is limited by the type and size of sampling and by its representativity of the entire lesion. Thus, the best diagnostic approach requires the integration ofclinical, morphological, and immunocytochemical information with imaging data (i.e. US pattern, perfusional pattern, helical computed tomography/magnetic resonance pattern). Molecular data are still under evaluation as to their diagnostic efficacy in this controversial field. Discrepancies have emerged recently between Eastern and Western interpretation of these lesions, particularly in the category of "borderline" nodules that are mostly labelled as early, well differentiated HCC by Eastern pathologists and as HGDN by Western pathologsts. Novel and more objective phenotypical and molecular markers are needed to discriminate within the grey area of borderline lesions that, epidemiologically, are likely distinct between Eastern and Western geographic areas. These tools might allow a better understanding of the boundaries of the process going from high grade dysplasia to in situ HCC and from the latter to microinvasive HCC and advanced HCC, for proper clinical management and optimal therapy.
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PMID:Hepatocellular dysplastic nodules. 1787 73

Hepatocellular carcinoma (HCC) is a highly invasive tumor characterized by vigorous neovascularization. The purpose of this study is to examine the expression of Twist, a highly conserved bHLH transcription factor that is known to promote EMT, and evaluate its effect on tumor angiogenesis and metastasis of HCC. The mRNA expression of Twist, VEGF, E-cadherin, and N-cadherin was determined by Real-Time RT-PCR in 30 pairs of hepatocellular carcinomas and matched non-cancerous tissues. Immunohistochemistry was carried out to analyze the protein expression of Twist, VEGF, E-cadherin, and N-cadherin in 40 hepatocellular carcinoma cases. The staining of endothelial cells for CD34 was used to evaluate the MVD. We found that Twist mRNA and protein were both increased in HCC as compared to non-cancerous tissues. The HCC specimens showing positive Twist expression had a higher microvessel density than those without Twist expression. And up-regulated Twist protein was significantly associated with intrahepatic and extrahepatic metastasis (p=0.048 and P=0.039 respectively). In addition, patients with Twist expression had poor prognosis. We also found that the expression of Twist positively correlated with up-regulation of VEGF and N-cadherin (P=0.002 and p=0.016 respectively), but not with downregulation of E-cadherin in HCC. Our results demonstrate that Twist may play an important role in the angiogenesis and metastasis of HCC. Twist expression may become a potential novel prognostic factor for the disease survival of HCC.
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PMID:Up-regulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. 1798 1

Non-invasive therapies for the treatment of hepatocellular carcinoma (HCC) would be of great benefit to public health. To this end, we have developed a platelet-derived growth factor-C (PDGF-C) transgenic (Tg) mouse model, which mimics many aspects of human liver carcinogenesis. Specifically, overexpression of PDGF-C results in liver fibrosis, which is preceded by activation and proliferation of hepatic stellate cells, and is followed by the development of dysplastic lesions and angiogenesis, and progression to HCCs by 8 months of age. Here, we show that PDGF-C overexpression induces the proliferation of endothelial-like cells that are present in tumors and adjacent non-neoplastic parenchyma. The protein tyrosine kinase inhibitor, imatinib (Gleevec), decreases the proliferation of non-parenchymal cells (NPC) in vitro and in vivo, with concomitant inhibition of Akt. In vivo treatment with imatinib also blocks the expression of CD34 in PDGF-C Tg mice. Decreased NPC proliferation and CD34 expression correlated with lower levels of active ERK1/2 and total levels of PDGF receptor alpha (PDGFRalpha). In summary, the small molecule inhibitor imatinib attenuates stromal cell proliferation in PDGF-C-induced HCC, which coincides with decreased expression of both CD34 and PDGFRalpha, and activated Akt. Our findings suggest that imatinib may be efficacious in the treatment of hepatocarcinogenesis, particularly when neovascularization is present.
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PMID:Targeting stromal cells for the treatment of platelet-derived growth factor C-induced hepatocellular carcinogenesis. 1799 42

Podoplanin, which is immunoreactive to D2-40 antibody, is reportedly expressed in lymphatic vessels in non-neoplastic tissues, and also in vascular and non-vascular tumors. However, its expression in non-neoplastic and neoplastic liver tissues has not been well documented. In this study, we examined podoplanin expression in specimens from 10 normal livers and 73 cases of liver tumors: hemangioma (16 cases), epithelioid hemangioendothelioma (9 cases), angiosarcoma (4 cases), angiomyolipoma (7 cases), hepatocellular carcinoma (11 cases), intrahepatic cholangiocarcinoma (11 cases), and metastatic liver cancer (15 cases). We compared levels of podoplanin and other endothelial markers (CD31, CD34, and factor VIII) in liver tumors. In the normal liver, podoplanin was expressed in lymphatic endothelium, nerve fibers, and mesothelium in the hepatic capsule, but not observed in any cells within hepatic lobules. Among liver tumors, podoplanin was specifically expressed in seven of nine cases (78%) of epithelioid hemangioendothelioma but not in other hepatic tumors. The expression of CD31, CD34, and factor VIII was observed in endothelial cells in all cases of hemangioma, epithelioid hemangioendothelioma, angiosarcoma, and angiomyolipoma with one exception, a case of epithelioid hemangioendothelioma which was without CD31 expression. Interestingly, the intensity of podoplanin expression was negatively correlated with the expression of CD34 and factor VIII. In conclusion, podoplanin would be useful as a diagnostic marker for epithelioid hemangioendothelioma in liver tumors.
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PMID:Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver. 1808 56

Sinusoidal alterations unrelated to primary hepatocellular damage present without characteristic clinical findings and in these cases the liver biopsy is particularly important. Capillarization of sinusoids is characterized by closing of fenestration, formation of a basal membrane and by the expression of CD34 and is typical for active cirrhosis. In nodular regeneratory hyperplasia, capillarization indicates a local or general disturbance of perfusion. In large regenerative nodules, focal nodular hyperplasia and liver cell adenoma CD34-positive capillaries reflect afferent parts and CD34-negative sinusoids the efferent parts of the parenchymal vascular bed. HCC generally have a completely capillarized CD34-positive vascular bed. Hepatic angiosarcomas and epithelioid hemangioendotheliomas can be easily overseen in liver biopsies, if they spread along the sinusoids without detoriation of the acinar architecture and without significant alteration of the surrounding liver cell plates. Toxic damage of endothelial cells, post-sinusoidal stasis and sinusoidal hyperperfusion are the underlying pathogenetic principles of sinusoidal injury. Rupture and loss of the perisinusoidal reticulin fibres lead to peliosis hepatis. In these cases liver biopsy might disclose occlusion of the terminal liver veins (VOD). Perisinusoidal fibrosis can be caused by intrasinusoidal accumulation of pathologic cells, advanced intrasinusoidal macrophagocytic storage diseases and by activation of the vitamin A-storing hepatic stellate cells. Perisinusoidal amyloidosis can be the first sign of an underlying B-cell neoplasia.
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PMID:[Pathology along the liver sinusoids: endothelial and perisinusoidal findings]. 1821 Jan 8


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