Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endostatin inhibits angiogenesis and tumor growth in mice. The role of its endogenous precursor collagen XVIII in human cancer is unknown. In normal tissues, two variants of collagen XVIII, namely, the short and long forms regulate tissue specificity, the long form being almost exclusively expressed by hepatocytes in the liver. We analyzed RNA arrays from 57 hepatocellular carcinomas (HCCs) with common and variant-specific probes and investigated the relationships between collagen XVIII expression and angiogenesis by measuring the CD34-positive microvessel density. Low collagen XVIII expression by tumor hepatocytes was associated with large tumor size (r, -0.63; P < 0.001) and replacement of trabeculae with pseudoglandular-solid architecture (chi2, 28; P < 0.001), which indicate tumor progression. Tumors expressing the highest collagen XVIII levels were smaller and had lower microvessel density (P = 0.01) than those expressing moderate levels; and HCCs with the lowest collagen XVIII levels approached a plateau of microvessel density, which indicated that a decrease in collagen XVIII expression is associated with angiogenesis in primary liver cancer. HCCs recurring within 2 years of resection showed 2.2-fold lower collagen XVIII mRNA than nonrecurring ones (P = 0.02). The findings relied on the hepatocyte-specific long form. Thus, the endogenous expression of the endostatin precursor decreases along with tumor progression in HCCs.
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PMID:Tumor progression is associated with a significant decrease in the expression of the endostatin precursor collagen XVIII in human hepatocellular carcinomas. 1119 95

To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression in 22 resected HCC, 8 cirrhotic and 8 control liver specimens were investigated by in situ hybridization and immunohistochemistry respectively, and the level of angiopoietin-2 and Tie2 expression in HCC were compared in terms of tumor biological parameters. It was found that CD34 was not expressed in control liver, expressed scarcely in cirrhotic liver (17.8 +/- 13.5/HP), but intensively expressed in HCC (86.3 +/- 34.8/HP, P < 0.01). Tie2 receptor was not expressed in controls, expressed at low level in cirrhotic liver (11.3 +/- 8.7/HP), while strongly positive in the microvascular endothelia of HCC (52.4 +/- 16.7/HP, P < 0.01). The level of Tie2 receptor expression in HCC was closely related with tumor diameter, angiogenesis and portal invasion. Angiopoietin-2 gene was not expressed in control liver, expressed mildly in cirrhotic liver (11.2 +/- 9.7/HP), but extensively in tumor zone (36.4 +/- 17.5/HP), the level of angiopoietin-2 expression was closely related with angiogenesis, portal invasion and histological grading of HCC. It is concluded that angiogenesis is increased in HCC; angiopoietin-2/Tie2 expression in human hepatic carcinoma is closely related with angiogenesis, which are probably involved in the HCC angiogenesis regulation, promoting the development and metastasis of human hepatic cancer.
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PMID:Expression of angiopoietin-2 gene and its receptor Tie2 in hepatocellular carcinoma. 1253 84

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

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

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

To develop a drug delivery system with enhanced efficacy and minimized adverse effects, we synthesized a novel polymeric nanoparticles, (YCC-DOX) composed of poly (ethylene oxide)-trimellitic anhydride chloride-folate (PEO-TMA-FA), doxorubicin (DOX) and superparamagnetic iron oxide (Fe(3)O(4)) and folate. The efficacy of the nanoparticles was evaluated in rats and rabbits with liver cancer, in comparison with free-DOX (FD) and a commercial liposome drug, DOXIL. YCC-DOX showed the anticancer efficacy and specifically targeted folate receptor (FR)-expressing tumors, thereby increasing the bioavailability and efficacy of DOX. The relative tumor volume of the YCC-DOX group was decreased two- and four-fold compared with the FD and DOXIL groups in the rat and rabbit models, respectively. Furthermore, YCC-DOX showed higher MRI sensitivity comparable to a conventional MRI contrast agent (Resovist), even in its lower iron content. In the immunohistochemical analysis, YCC-DOX group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC-DOX group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. These results indicate that YCC-DOX is a promising candidate for treating liver cancer and monitoring the progress of the cancer using MRI.
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PMID:Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. 2034 38

In our earlier work, we demonstrated that agrin, a multifunctional heparan sulfate proteoglycan, accumulates in hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC). In addition, we proved the utility of agrin immumohistochemistry in discriminating between HCCs and benign parenchymal lesions. Here, we have examined the expression of agrin in metastatic liver carcinomas in comparison with primary liver tumors. Immunohistochemistry for agrin was performed on 25 HCC, 16 intrahepatic CCC, 20 colorectal cancer metastasis (CRCm), and 18 pancreatic ductal carcinoma metastasis (PDCm) samples and evaluated with both quantitative and qualitative methods. Agrin/CD34 double immunofluorescent staining was carried out on snap-frozen sections. Agrin mRNA expression was measured in 11 HCC, 7 CCC, 11 CRCm, and 12 normal liver tissues. Regardless of tumor grade, agrin immunostaining was strong in the microvessels of HCCs. As opposed to HCC, agrin immunostaining was faint or nearly absent from the CD34-positive microvessels of CCC, CRCm, and PDCm; rather, it was detected in the basement membranes surrounding tumor cell pseudoglandules. While agrin was preserved in the basement membranes of Grade III CCCs, it was nearly absent from poorly differentiated metastatic adenocarcinomas. Agrin mRNA levels were the highest in CCC and lower, but still elevated in HCC and CRCm. By qualitative evaluation of agrin immunoreactions, CCC was differentiated from CRCm and PDCm with a sensitivity of 0.81 and a specificity of 0.82. HCCs were unequivocally identified on the basis of microvascular agrin labeling. Thus, agrin immunohistochemistry may facilitate determination of primary versus metastatic origin in problematic liver cancer cases.
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PMID:Agrin immunohistochemistry facilitates the determination of primary versus metastatic origin of liver carcinomas. 2047 64

We assessed the safety and efficacy of sorafenib with cryotherapy (cryoRx) in advanced hepatocellular carcinoma (HCC). One hundred four HCC patients were enrolled, who met the following criteria: (i) Barcelona Clinic Liver Cancer stage C; (ii) HCC without distant metastasis; (iii) the presence of portal vein thrombosis (PVT); (iv) Child-Pugh class A or B; and (v) life expectancy of at least 12 weeks. The patients were randomly divided into sorafenib-cryoRx and sorafenib (control) groups. Primary endpoint was time to progression (TTP); secondary endpoints included overall survival (OS) and tolerability. Microvessel density (MVD) was assessed by CD34-immunostaining. After a median 10.5 (4-26) months follow-up, the data showed that median TTP was 9.5 (8.4-13.5) months in combinatorial therapy group vs. 5.3 (3.8-6.9) months in sorafenib group (P = 0.02). The median OS was 12.5 (95 % CI 10.6-16.4) months in combination therapy group vs. 8.6 (7.3-10.4) months in sorafenib group (P = 0.01). Low MVD patients in combination therapy exhibited significantly longer median TTP and OS than controls. High MVD was predictive of poor responses to sorafenib. CryoRx did not increase frequency/degree of sorafenib-related adverse events. Therefore, it was concluded that the addition of cryoRx significantly improved clinical outcomes of Sorafenib therapy in advanced HCC with acceptable tolerance and similar safety profiles as previously reported.
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PMID:Cryotherapy is associated with improved clinical outcomes of Sorafenib therapy for advanced hepatocellular carcinoma. 2247 32


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