Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ki-67 antigen is detected in proliferating cells in all phases of the cell division cycle. Throughout most of interphase, the Ki-67 antigen is localised within the nucleous. To learn more about the relationship between the Ki-67 antigen and the nucleolus, we have compared the distribution of Ki-67 antibodies with that of a panel of antibodies reacting with nucleolar components by confocal laser scanning microscopy of normal human dermal fibroblasts in interphase stained in a double indirect immunofluorescence assay. During early G1, the Ki-67 antigen is detected at a large number of discrete foci throughout the nucleoplasm, extending to the nuclear envelope. During S-phase and G2, the antigen is located in the nucleolus. Double indirect immunofluorescence studies have revealed that during early to mid G1 the Ki-67 antigen is associated with reforming nucleoli within discrete domains which are distinct from domains containing two of the major nucleolar antigens fibrillarin and RNA polymerase I. Within mature nucleoli the Ki-67 antigen is absent from regions containing RNA polymerase I and displays only partial co-localisation within domains containing either fibrillarin or B23/nucleophosmin. Following disruption of nucleolar structure, induced by treatment of cells with the drug 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole or with actinomycin D, the Ki-67 antigen translocates to nucleoplasmic foci which are associated with neither fibrillarin nor RNA polymerase I. However, in treated cells the Ki-67 Ag remains associated with, but not co-localised to, regions containing B23/nucleophosmin. Our observations suggest that the Ki-67 antigen associates with a fibrillarin-deficient region of the dense fibrillar component of the nucleolus. Integrity of this region is lost following either nucleolar dispersal or nucleolar segregation.
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PMID:Localisation of the Ki-67 antigen within the nucleolus. Evidence for a fibrillarin-deficient region of the dense fibrillar component. 879 15

Endoglin/CD105 is a membrane protein involved in the TGF-beta receptor signalling pathway. Endoglin expression has been reported to be selective for a few cell types, in particular endothelial cells, although a number of conflicting reports have been published. In this study, we performed a detailed analysis of endoglin expression in human lung tumors and different tumor and endothelial cell lines, employing reverse-transcriptase-polymerase-chain reaction as well as immunoblotting and immunohistochemistry using verified antibodies to endoglin. Our data show a clearly preferential expression of both endoglin mRNA and protein in endothelial cells. In tumors, endoglin expression was strongly elevated in the angiogenic endothelium at the tumor edges. In agreement with this observation, we find a clear correlation between endoglin expression and markers of proliferation, such as cyclin A and Ki-67, suggesting that endoglin expression is linked to cell-cycle regulation. These findings not only resolve some of the discrepancies in the literature, but also provide the basis for further applications making use of its selective localization and expression in the tumor vasculature.
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PMID:Elevated expression of endoglin, a component of the TGF-beta-receptor complex, correlates with proliferation of tumor endothelial cells. 1022 46

Interferon gamma (IFN-gamma) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-gamma exerts its pleiotrophic effects by transcriptional regulation of expression of numerous genes, such as major histocompatibility complex (MHC) class I and Fas, through interaction with IFN-gamma receptor (IFN-gamma-R). Although hepatocytes in normal liver express weak or no IFN-gamma-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-gamma-R alpha-chain knock-out mice revealed the actions of IFN-gamma on tumor cells as an extrinsic tumor-suppressor mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC) blocks the signal transduction of IFN-gamma to evade host immune surveillance. We examined the expression of IFN-gamma-R and IFN-gamma-inducible genes in 44 cases with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-gamma-R expression on the cell surface was up-regulated in 27 cases. In IFN-gamma-R-negative cases (n = 15), tumor size was larger (P =.032), serum alpha-fetoprotein (AFP) level was higher (P =.001), intrahepatic and extrahepatic metastasis was more common (P =.044 and.013, respectively), and Ki-67 labeling index (LI) was higher (P =.041), compared with IFN-gamma-R-positive cases. Accordingly, the evasion mechanism may play an important role in progression, especially metastasis, in HCC. The significant correlation between the status of IFN-gamma-R and the expression of Fas and MHC implies that the loss of IFN-gamma-R might contribute to the mechanism of escape from host immune rejection in HCC.
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PMID:The impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma. 1096 Apr 40

Microvessel density (MVD) was estimated in a series of 202 vertical growth phase (VPG) melanomas and 68 corresponding metastases, using a marker for angiogenic endothelial cells (CD105) and Factor-VIII. The expression pattern of vascular endothelial growth factor (VEGF), FLT-1, KDR and thrombospondin-1 (TSP-1) was studied by immunohistochemistry, in situ hybridization and reverse-transcriptase polymerase chain reaction. CD105 stained significantly less vessels, but gave only limited additional prognostic information compared with Factor-VIII, and MVD was an independent prognostic factor for both markers. Ninety-eight percent of all cases showed expression of VEGF, and higher expression was found significantly more frequent in thinner and less vascularized tumors. Possible autocrine loops were suggested by co-expression of VEGF and its two receptors in tumor cells, and by a significant correlation between KDR and tumor cell proliferation (Ki-67) in the subgroup of thicker tumors. Staining of VEGF receptors in endothelium was not correlated with MVD. Strong expression of TSP-1 in tumor stroma was found in 43% of the primary tumors, and was significantly correlated with increased thickness, proliferation and MVD, as well as decreased survival. These data suggest that MVD is associated with prognosis in cutaneous melanomas, and that the VEGF system and particularly TSP-1 seem to be involved in the regulation of angiogenesis and progression of these tumors.
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PMID:Expresson of vascular endothelial growth factor, its receptors (FLT-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. 1143 69

Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse-transcriptase polymerase chain reaction (RT-PCR) using enhanced real-time PCR was applied to look for evidence of SARS-associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki-67. RT-PCR showed evidence of SARS-associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro- or macro-vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS-associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course.
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PMID:SARS-associated viral hepatitis caused by a novel coronavirus: report of three cases. 1476 79

This paper discusses the diversity of synovial sarcomas (SSs) [biphasic (BSS), monophasic fibrous (MFSS), and poorly differentiated (PDSS)] and tissue microarray (TMA) evaluation of the immunophenotypic and histological progression of SSs in nude mice using three TMAs comprising 11 primary SSs (8 MFSSs, 2 BSSs, and 1 PDSS) and their xenografts. BSS and MFSS progressively transformed to a similar undifferentiated phenotype with loss of glandular component in the xenografts. Epidermal growth factor receptor and SALL2 were expressed in primary tumors and xenografts. Enhanced bcl-2 and bax expression were noted in xenografts. Ki-67 overexpression in xenografts correlated with high mitotic index. Epithelial membrane antigen (EMA) and cytokeratin AE1/AE3 were detected in all original and xenografted SSs. Hierarchical clustering differentiated original MFSS and BSS, but their xenografts clustered together due to similar immunoexpression profile. Our study demonstrates definite phenotypic variability of BSS and MFSS in the xenografts. Differences in immunoexpression for various markers existed between primary tumor and xenografts but not between subtypes. Hierarchical clustering grouped TMA immunostaining data and confirmed immunophenotypic variability; however, it failed to reveal any immunophenotypic differences between SYT-SSX1 and SYT-SSX2 type tumors. Nonetheless, reverse-transcriptase-polymerase chain reaction detected SYT-SSX transcripts in all primary SSs and their xenografts, thereby demonstrating their genetic stability.
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PMID:Tissue microarray profiling of primary and xenotransplanted synovial sarcomas demonstrates the immunophenotypic similarities existing between SYT-SSX fusion gene confirmed, biphasic, and monophasic fibrous variants. 1695 34

Non-alcoholic fatty liver disease (NAFLD) is a common problem with a wide variety of phenotypes. While its pathogenesis is still not fully understood, several risk factors for disease progression have been identified. Therefore, defining adequate animal models may serve to unreveal the pathogenesis in NAFLD. We studied Lewis and Sprague-Dawley rats of both genders (n = 6) fed standard (Std) or high-fat (HF) diet for three weeks. Disease stage was assessed by haematoxylin-eosin, Azan Heidenheim and Oil-Red staining, apoptosis by single-stranded DNA (ssDNA) detection and liver regeneration by Ki-67 staining. Serum markers of liver injury and lipid metabolism including adipocytokines were analysed. Livers of both strains and genders fed with HF diet demonstrated evidence of steatosis. Lewis rats developed microvesicular steatosis whereas Sprague-Dawley rats presented macrovesicular steatosis accompanied by pronounced fibrosis. Female gender of both strains was associated with lower steatosis grade and higher proliferation rate (P < 0.05). Gender-specific differences were most prominent in Lewis rats on a HF diet, where females showed lower alkaline phosphatase, cholesterol, triglyceride and leptin levels and a more favourable low-density lipoprotein/high-density lipoprotein ratio than males (P < 0.05). Reverse transcriptase-polymerase chain reaction analysis was performed to demonstrate changes in expression of various genes important for liver regeneration, fibrosis and steatosis. HF diet induced downregulation of proangiogenic genes such as vascular endothelial growth factor receptor 1 and 2 (P < 0.05) in males was not present in females. In conclusion, strain and gender served major roles in disease progression. These differences should be considered when designing studies and may offer new ways to advance therapeutic strategies.
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PMID:Gender and strain-specific differences in the development of steatosis in rats. 2346 89

We report a case of a longstanding, large tumor involving spinal nerve roots of the cauda equina. The tumor showed small round cells arranged in nests and cords and immunophenotypic features of a glomus tumor, along with infrequent mitoses and a low Ki-67 labeling index, but exhibited some rosette-like structures, with focal CD99 and Neu-N expression. Subsequent molecular analysis showed the presence of an EWSR1-WT1 gene fusion by fluorescence in situ hybridization, which was confirmed by reverse- transcriptase polymerase chain reaction. To our knowledge, this is the first case reported with EWSR1-WT1 fusion in a small round blue cell tumor with smooth muscle differentiation and an indolent course.
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PMID:Low-grade small round cell tumor of the cauda equina with EWSR1-WT1 fusion and indolent clinical course. 2545 78

CDK7 has been known as a component of CDK activating kinase (CAK) complex, the complex was composed of CDK7, Cyclin H and RING finger protein Mat1 that contribute to cell cycle progression by phosphorylating other CDKs. In addition, the complex is also an essential component of general transcription factor TFIIH which controls transcription via activating RNA polymerase II by serines 5 and 7 phosphorylation of the carboxyl-terminal domain (CTD) of its largest subunit. However, the role of CDK7 in the pathogenesis of gastric cancer has not been identified. Our study showed that CDK7 was significantly upregulated and positively correlated with tumor grade, infiltration depth, lymph node, Ki-67, and predicted poor prognosis in 173 gastric cancer specimens by immunohistochemistrical analyses. Furthermore, in vitro results indicated that CDK7 promoted proliferation of gastric cancer cells by CCK8, clone formation analyses and flow cytometric analyses, while CDK7 knockdown led to decreased cell proliferation. Our study will provide a theoretical basis for the study of CDK7 in gastric cancer.
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PMID:Upregulation of CDK7 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis. 2715 49

Cleft palate is a common congenital abnormality that results from defective secondary palate (SP) formation. The Sine oculis-related homeobox 2 (Six2) gene has been linked to abnormalities of craniofacial and kidney development. Our current study examined, for the first time, the specific role of Six2 in embryonic mouse SP development. Six2 mRNA and protein expression were identified in the palatal shelves from embryonic days (E)12.5 to E15.5, with peak levels during early stages of palatal shelf outgrowth. Immunohistochemical staining (IHC) showed that Six2 protein is abundant throughout the mesenchyme in the oral half of each palatal shelf, whereas there is a pronounced decline in Six2 expression by mesenchyme cells in the nasal half of the palatal shelf by stages E14.5-15.5. An opposite pattern was observed in the surface epithelium of the palatal shelf. Six2 expression was prominent at all stages in the epithelial cell layer located on the nasal side of each palatal shelf but absent from the epithelium located on the oral side of the palatal shelf. Six2 is a putative downstream target of transcription factor Hoxa2 and we previously demonstrated that Hoxa2 plays an intrinsic role in embryonic palate formation. We therefore investigated whether Six2 expression was altered in the developing SP of Hoxa2 null mice. Reverse transcriptase PCR and Western blot analyses revealed that Six2 mRNA and protein levels were upregulated in Hoxa2^-/- palatal shelves at stages E12.5-14.5. Moreover, the domain of Six2 protein expression in the palatal mesenchyme of Hoxa2^-/- embryos was expanded to include the entire nasal half of the palatal shelf in addition to the oral half. The palatal shelves of Hoxa2^-/- embryos displayed a higher density of proliferating, Ki-67 positive palatal mesenchyme cells, as well as a higher density of Six2/Ki-67 double-positive cells. Furthermore, Hoxa2^-/- palatal mesenchyme cells in culture displayed both increased proliferation and elevated Cyclin D1 expression relative to wild-type cultures. Conversely, siRNA-mediated Six2 knockdown restored proliferation and Cyclin D1 expression in Hoxa2^-/- palatal mesenchyme cultures to near wild-type levels. Our findings demonstrate that Six2 functions downstream of Hoxa2 as a positive regulator of mesenchymal cell proliferation during SP development.
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PMID:Six2 Plays an Intrinsic Role in Regulating Proliferation of Mesenchymal Cells in the Developing Palate. 2921 17


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