Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extracellular matrix (ECM) located in and around tumors is different from normal organ stroma, and there is evidence that it is critically involved in carcinogenesis and malignant growth. Whereas an abnormal composition of ECM in hepatocellular carcinomas (HCC's) has previously been demonstrated, not much is known so far with respect to putative HCC precursor lesions. We have, therefore, systematically analyzed the immunohistochemical reactivity for two major ECM components, tenascin and type IV collagen, in three types of liver cell dysplasia (LCD), and compared the findings with patterns observed in HCC's of different types and grades. Tenascin reactivity was generally stronger in HCC's than in cirrhosis. In cirrhotic nodules harboring areas of LCD, tenascin expression was significantly lower in small cell LCD than in large cell LCD. Type IV collagen reactivity in and around HCC's decreased as a function of a lower differentiation grade. In both groups of cirrhosis, i.e. with or without HCC, cirrhotic nodules occupied by the small cell variant of LCD exhibited a significantly lower type IV collagen reactivity than those with large cell LCD or simple regenerative cells. Taken together these findings suggest that, similar to adenomatous hyperplasia, small cell LCD is characterized by an abnormal tenascin and type IV collagen expression, thus reflecting the defective ECM pattern observed in HCC's.
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PMID:Tenascin and type IV collagen expression in liver cell dysplasia and in hepatocellular carcinoma. 886 54

In the last decade, careful examination of explanted cirrhotic livers in liver transplant centers around the world has confirmed the findings of the earlier Japanese investigators: DNs (by this or any other name) represent hepatic, premalignant lesions in chronic liver disease. Careful examination of their gross and microscopic morphologies has led to the hypothesis of precirrhotic, spreading clonal expansions that are resistent to scarring, and that result in neoplastic islands of hepatic parenchyma. The resultant distinctive nodules, often marked by features suggestive of their clonality (such as increased pigment), are at increased risk for subsequent carcinomatous events, thereby giving rise to HCC. Specialized molecular and immunohistochemical studies confirm many aspects of this hypothesis. In suggesting that some aspects of DN pathophysiology are not integral to the carcinogenetic pathway (i.e., inhibition of HSC inactivation), this hypothesis serves a broader purpose, explaining the various settings in which early HCCs are found in cirrhotic explants and in wedge resections of radiographically defined lesions. Discrepancies between Japanese and non-Japanese investigations regarding dysplasia and early HCCs reflect not different biologic pathways but differences in detection, interpretation, and application of nomenclature. These differences may fade away as more international collaborative work brings investigators of diverse nationalities into regular contact, supporting movement toward a commonly acceptable nomenclature and set of diagnostic criteria. Ultimately, an understanding of the pathophysiology of these lesions, through more detailed molecular and physiologic studies, should lead to more efficient and available early detection, and perhaps chemoprevention approaches to hepatic malignancy.
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PMID:Dysplastic nodules and hepatocarcinogenesis. 1212 67

Cirrhosis of the liver has to be regarded as a premalignant condition independent of its etiology. The annual risk of developing HCC in cirrhosis is between 1% and 6%. Surveillance-programs have been introduced to detect early stages of HCC in order to improve mortality. However, only controlled trials will answer the question of the efficacy of such programs. Studies on the potential benefit of surveillance-programs comparing survival in surveilled and unsurveilled patients are so far lacking. It seems clear, however, that surveillance-programs can detect small tumors, often unfocal and potentially treatable by a curative approach. Moreover, the etiology (HBV, HCV, genetic hemochromatosis) and activity of liver cirrhosis as measured by serum-transaminases, liver histology (small-cell dysplasia and atypical regenerative nodules), Child-Pugh-stage and the concentration of alpha-fetoprotein at the beginning of a surveillance-program--all these factors reflect a high risk of developing HCC in an individual patient. Until programs are introduced on the basis of randomized, controlled trials of surveillance vs. usual care (with liver-related, specific deaths and all-cause-mortality as end-points) it seems reasonable to screen high-risk patients semi-annually by liver ultrasound and determination of AFP-concentration in the serum.
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PMID:[Hepatocellular carcinoma: risk groups--screening]. 1223 79

P-Glycoprotein and C-MOAT are important hepatic transport proteins which play a role in handling anticancer drugs. Hepatocellular carcinoma is a common hepatic malignancy that is relatively resistant to chemotherapeutic drugs. We therefore studied the expression of these two transport proteins in liver sections from hepatocellular carcinoma by immunohistochemistry and compared the reactivity to that in other liver conditions, including cirrhosis and dysplasia. We studied 53 sections from 17 liver specimens and found that the majority of samples stained positively for both P-glycoprotein and C-MOAT; however, the degree of staining was less in HCC and hepatic adenoma than in liver adjacent to HCC or in cirrhosis or dysplastic nodules. HCC with a compact pattern had less staining than those with acinar, scirrhous, or trabecular patterns. The location of both P-glycoprotein and C-MOAT staining was a function of the liver lesion present. Thus, most tissues without hepatocellular carcinoma showed foci of globular canalicular staining, whereas a delicate linear pattern of canalicular staining was most common overall. We conclude that expression of P-glycoprotein and C-MOAT, as detected by qualitative immunohistochemical evaluation are little affected by the development of HCC and therefore are probably of little clinical significance for management of malignancy.
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PMID:Expression of P-glycoprotein and C-MOAT in human hepatocellular carcinoma: detection by immunostaining. 1245 78

The natural history of hepatitis C virus (HCV) infection has a highly variable course. Many patients develop chronic infection, with its consequent risk of cirrhosis, liver failure and hepatocellular carcinoma. A key question is whether patients at high risk of disease progression can be distinguished from those with relatively benign disease course. The disease progression is influenced by other factors such as duration of infection, age at infection, sex, co-infection with hepatitis B virus (HBV), Epstein Bar virus (EBV), cytomegalovirus (CMV), the level of HCV viraemia and its type. Other endemic infections in the community as bilharziasis may have a role in progression of the condition to serious complications. These factors are correlated with newly proposed grades and stages of the disease. The studied (109) cases were divided into 6 groups according to the concomitant infection with HCV. The result proved that groups 1, 3 & 5 had a higher level of viraemia than other groups, and to be the high-risk groups as 56.4% and 34.6% were in G2S2 and G3S3, respectively. All cases of liver cell dysplasia and hepatocellular carcinoma in this study were seen in these groups. The conclusion showed that these factors play an important role in the progression of HCV infection. Death of the patients of this progressive condition occurs in younger age and is more due to liver failure than to HCC.
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PMID:HCV and associated concomitant infections at Sharkia Governorate, Egypt. 1512 52

Ethanol consumption represents a major risk factor for cancer development, and a significant fraction of hepatocarcinomas arises in alcoholic liver cirrhosis. Increasing evidence indicates that ethanol acts as a tumor promoter on genetically initiated cells, by increasing the intracellular concentration of reactive oxygen species and promoting tissue necrosis/regeneration and cell proliferation. The tumor suppressor p53 restrains the expansion of carcinogen-initiated cells by inducing cell cycle arrest and apoptosis; accordingly, p53-deficient mice develop spontaneous and chemically induced neoplasms at a much higher frequency than normal mice. In normal mice exposed to a subacute (3 weeks) ethanol intoxication, a significant increase in the number of apoptotic hepatocytes was observed in concomitance with the up-regulation of the mitochondrial superoxide scavenger MnSOD, a reliable indicator of oxidative stress. Cell death occurred in the absence of liver inflammation and necrosis. Ethanol-induced hepatocyte apoptosis was completely abrogated in the p53 null background, suggesting that the tumor suppressor is necessary for hepatocyte death by ethanol. Accordingly, p53 -/- MEF were, unlike wild type cells, completely insensitive up to 0.5M ethanol in the culture medium. Strikingly, marked and widespread signs of dysplasia, with nuclear pleomorphisms and initial loss of normal architecture, heralding malignant transformation, were scored in all the mutant mice exposed to ethanol, but not in the control-fed littermates nor in ethanol-fed normal mice. These observations suggest that p53-dependent apoptosis restrains the tumorigenic effect of ethanol on liver cells, in agreement with the frequent loss of p53 function in HCC, and reveal an unexpected carcinogenic potential of alcohol which appears to be independent from the induction of cirrhosis and hepatocyte regeneration.
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PMID:Abrogation of hepatocyte apoptosis and early appearance of liver dysplasia in ethanol-fed p53-deficient mice. 1552 6

Several tumour entities have been described to develop in chronic inflammatory disease mainly hepatocellular carcinoma in chronic hepatitis. Compared to HCC bile duct carcinomas or other tumour entities are rare. The risk for HCC increases if liver cirrhosis occurred. Despite a huge progress in detecting many genes involved and altered in hepatocarcinogenesis the exact mechanisms of HCC development is not understood. Various causes initiate a multistep process of several steps: chronic liver injury, chronic inflammation, cell death, regeneration, cirrhosis, DNA damage, dysplasia and HCC. Molecular changes cannot be used for risk assessment of patients with liver cirrhosis or liver cell dysplasia. They are not helpful for problems in differential diagnosis between dysplasia and HCC.
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PMID:[Tumours and inflammatory liver diseases]. 1803 86

The multistep process of hepatic carcinogenesis is mirrored by the morphologic classification of lesions detectable in cirrhosis, that include large regenerative nodules (LRN), low grade dysplastic nodules (LGDN) and high grade dysplastic nodules (HGDN). The latter belong to the "bordeline malignancy" cathegory requiring an accurate distinction from well-differentiated and early hepatocellular carcinoma. Nodules in cirrhosis are usually detected by non-invasive imaging techniques, being the latter 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 US detectable nodules. The histologic diagnosis on liver samples is based on the accurate search of a set of cyto-architectural features (cell atypia, cell crowding, trabecular thickness, microacini etc) 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 (HSP70 and Glipican 3 among others). Still, the diagnostic sensitivity is limited by the type and size of sampling and by its representativity of the entire lesion. The best diagnostic approach thus requires the integration of clinical, morphological and immunocytochemical information with imaging data (US pattern, perfusional pattern, helical CT/MR 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 cathegory of "borderline" nodules, that are mostly labelled as early, well differentiated HCC by eastern pathologists and as HGDN by western pathologists. 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 a proper clinical management and optimal therapy.
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PMID:Hepatocellular dysplastic nodules. 1872 69

Recent advances in the understanding of HCC heterogeneity have shown not only distinct molecular classes with potential therapeutical implications but also have suggested that subclasses might be mirrored by tumour morphology and phenotype. The classification of HCC is therefore shifting from a more traditional, morphology-based approach to a more functional approach with clinical implications. The classical histological patterns (trabecular, pseudoglandular, solid, etc.) are still taken into account but in combination with other parameters such as cell grading, clonal changes, type and extent of vascularisation, tumour immunophenotype etc. This array of morpho-phenotypical features is expected to ultimately provide information about cell of origin, tumour behaviour and, hopefully, treatment sensitivity. In this chapter we will give a brief overview on modern principles of hepatic carcinogenesis by outlining the events/lesions bridging the microscopic dysplasia to advanced HCC. In this context special emphasis will be given to novel concepts and diagnostics and differential diagnosis of small HCC (of early and progressed type), which is the main target of the surveillance in the cirrhotic population. Novel and emerging subpopulations of HCC will also be considered, for example HCC with stem/progenitor cell phenotype and mixed hepatobiliary forms which are filling the traditional separation between two entities (HCC and cholangiocarcinoma), likely more inter-related than previously thought.
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PMID:Histopathological classification of hepatocellular carcinoma. 2054 8

The aim of this study was to investigate the expression rates of CD133 and CD90 in cirrhosis-dysplastic nodule-HCC (Crh-DN-HCC) sequence related to the etiologic background. Thirty-five HCC, 8 small cell dysplasia (SCD), and 63 cases of cirrhosis having different etiologies were collected. Immunohistochemical expressions of CD133 and CD90 were evaluated. CD133 positivity was higher in HCC cases with chronic hepatitis B and CD90 with chronic hepatitis C. The highest staining rate was seen in poorly differentiated HCC cases. Only one SCD case and almost half of the cirrhotic cases which were stained for CD133 were associated with hepatitis B; none was stained for CD90. Increased CD133 expression indicated a significantly shorter overall survival rate. No significant relationship was detected between the expression rates of CD133 or CD90 and other parameters. In this study, which investigates the immunohistochemical expression profiles of CD133 and CD90 through Crh-DN-HCC sequence, the highest staining rate was detected in HCC. It is rational to try to elucidate the earliest events in hepatocarcinogenesis by studying SCD. It is important to be aware of this issue in daily practice, which will provide a deeper insight into the understanding of the effects of CSCs in the progression and management of HCC.
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PMID:Investigation of diagnostic utility and expression profiles of stem cell markers (CD133 and CD90) in hepatocellular carcinoma, small cell dysplasia, and cirrhosis. 2470 84


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