Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunohistochemical detection of the c-erbB-2 oncopeptide (p185erbB2) has been shown to be a valid marker for over-expression of this oncogene. To evaluate the possible relevance of gene expression to the proliferation of hepatocytes and bile ducts in human disease, the authors applied a monoclonal anti-p185 antibody to formalin-fixed, paraffin-embedded tissues from 67 examples of benign proliferative and neoplastic hepatic lesions and fetal liver. Focal membrane-based reactivity for the oncopeptide was detected on tumor cells in two of eight hepatocellular carcinomas and on tumor cells and adjacent bile ducts and hepatocytes in four of six cholangiocarcinomas. Each of the latter four lesions were in patients with primary sclerosing cholangitis. No reactivity was obtained in examples of hepatoblastoma, mixed cholangiocarcinoma-hepatocellular carcinoma, bile duct adenoma, or hepatocellular adenoma. Weak staining for p185erbB2 also was seen in two of seven cases of (sub)massive hepatic necrosis and two examples of postnecrotic cirrhosis, all of which were secondary to either hepatitis B or C virus infection. No other benign proliferative lesions were labeled by the anti-p185 antibody, including cases of chronic allograft rejection, necrosis secondary to hepatic artery thrombosis, metabolic-associated and nonmetabolic-associated cirrhosis, focal nodular hyperplasia, and nodular regenerative hyperplasia. The authors' results indicate that c-erbB-2 may be amplified in specific neoplastic and hepatitis B virus and hepatitis C virus infectious lesions of liver. The authors postulate that: (1) c-erbB-2 immunoreactivity may be a marker for malignant transformation in primary sclerosing cholangitis; and 2) overproduction of p185erbB2 may be an epiphenomenon of hepatitis B virus or hepatitis C virus infection.
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PMID:Immunoreactivity for c-erbB-2 oncopeptide in benign and malignant diseases of the liver. 137 19

Recently cervical cancer is defined as a sexually-transmitted disease, and human papillomavirus (HPV) has been focused as one of its etiologic agents. It is known that cervical cancer is extraordinarily rare in non-human mammals that have the estrous cycle. In contrast, cervical cancer is frequent in human beings which have lost the estrous cycle, and subsequently evolved a sexual behavior irrespective of the menstrual phase. Therefore, upon the hypothesis that the estrous cycle is a period protected from a sexually transmitted disease, we studied the status of local defence mechanism and growth/differentiation of normal cervical epithelium during the menstrual cycle and pregnancy. Then, the influence of HPV-infection on the growth and differentiation of cervical epithelium was analyzed. As a local immune system of the cervix, both IgA and IgG are secreted in the cervical mucus, and the levels in the follicular phase were significantly higher than those during the luteal phase and pregnancy. An existence of local defence mechanism in the follicular phase is suggested. Analysis of a cell proliferation antigen Ki-67 in normal cervix revealed that parabasal cells enter the cell cycle more frequently in the luteal phase than in the follicular phase. Basal and reserve cells are usually resting, but a few cells enter the cell cycle during the luteal phase and during pregnancy. Since cycling cells are more susceptible to viral infection, the basal and/or reserve cells during the luteal phase and pregnancy are suggested to be under the risk for HPV infection. As factors regulating growth and differentiation of cervical squamous epithelium, immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor (EGFR), c-erbB-2 protein, adult T-cell leukemia-derived factor (ADF), and HPV DNA was examined. In normal cervix, basal cells were usually ER-positive and PR-negative. Parabasal cells were ER-positive and PR-negative in the follicular phase, while they were ER-negative and PR-positive during the luteal phase and pregnancy. Considering the results of Ki-67 expression, the ER-negative and PR-positive status is possibly related to the proliferation of the cervical squamous epithelium. In cervical condylomas, basal cells infected by HPV6/11 were ER-positive, but HPV16/18-infected cells were ER-negative. Neoplastic cells of CINs and invasive squamous carcinomas containing HPV DNA 16/18 were ER-negative, while those containing HPV DNA 31/33/35 were weakly ER-positive. PR was positive in 2 of 2 condylomas, 18 of 26 CINs, and 13 of 22 invasive carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on pathogenesis of cervical carcinoma based on the analysis of growth and differentiation mechanism of cervical epithelium]. 217 18

The 9E3/CEF4 gene codes for a chemokine that is highly homologous to human interleukin-8 and melanoma growth-stimulating activity/groalpha. These chemokines belong to a family of molecular mediators that are importantly involved in inflammation, wound healing, tumor development, and viral entry into cells. On the chorioallantoic membrane the 9E3 protein is chemotactic for monocyte/macrophages and lymphocytes and is angiogenic. In cultured chicken embryo fibroblasts, which have many of the properties of wound fibroblasts, the gene is stimulated by a variety of agents including oncogenes, growth factors, phorbol esters, and thrombin. The strong stimulation of 9E3 by thrombin in culture correlates well with the observation that in young chicks this gene is stimulated to very high levels in fibroblasts upon wounding and remains high throughout wound repair. Activation of 9E3 by thrombin: (i) occurs very rapidly, one minute exposure to thrombin is sufficient to initiate the signals necessary for gene activation; (ii) is independent of mitogenesis; (iii) operates through the proteolytically activated receptor for thrombin; (iv) is mediated by tyrosine kinases, including c-src and the epidermal growth factor (EGF) receptor, rather than Ser/Thr kinases such as protein kinase C and protein kinase A. Inhibition of either c-src or the EGF receptor tyrosine kinase inhibits the stimulation of 9E3 by thrombin. We show here for the first time that activation of the EGF receptor through a cell-surface receptor that does not have tyrosine kinase activity can lead to expression of an immediate early response gene which encodes for a secreted protein, a chemokine. This rapidly activated tyrosine kinase pathway may be a general stress response by which in vivo a localized cell population reacts to emergency situations such as viral infection, wounding, or tumor growth.
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PMID:Thrombin aivation of the 9E3/CEF4 chemokine involves tyrosine kinases including c-src and the epidermal growth factor receptor. 947 78

The study was based on the biopsy material collected in Eastern coastal region of South Africa with high incidence of primary hepatocellular carcinoma (HCC). Forty-one patients were between 9 and 25 years old of the total number of 474 cases of HCC available for examination. Liver biopsies were fixed in 10% of neutralised formalin, processed to paraffin blocks, cut and stained with hematoxylin and eosin, silver reticulin, Masson trichrome and Prussian blue stains. Representative biopsies of 21 patients younger than 25 years and 56 older than 35 years were in addition examined immunohistochemically with HBsAg antibody, endothelial marker (F VIII-related antigen) and for oncoproteins c-myc and c-erbB-2 using peroxidase-antiperoxidase method. Cirrhotic liver was evident in 41.5% of all patients and in 28% of younger than 25 years. Hemosiderosis of the liver of patients over 35 years was nearly twice as common as in younger than 25 years and showed the opposite relationship to the presence of HBsAg in liver tissue. Oncoprotein expression was also higher in tumor tissue of younger patients. These results indicate the etiological association of HCC with HBV infection, cirrhosis and possibly siderosis of the liver with HCC. Simultaneous expression of oncoproteins and HBsAg indicate the primary importance of viral infection in etiopathogenesis of HCC.
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PMID:Hepatocellular carcinoma in young patients. 2159 36

Influenza virus is an RNA virus encapsulated in a lipid bilayer derived from the host cell plasma membrane. Previous studies showed that influenza virus infection depends on cellular lipids, including the sphingolipids sphingomyelin and sphingosine. Here we examined the role of a third sphingolipid, glucosylceramide, in influenza virus infection following clustered regularly interspaced short palindromic repeats with Cas9 (CRISPR-Cas9)-mediated knockout (KO) of its metabolizing enzyme glucosylceramidase (GBA). After confirming GBA knockout of HEK 293 and A549 cells by both Western blotting and lipid mass spectrometry, we observed diminished infection in both KO cell lines by a PR8 (H1N1) green fluorescent protein (GFP) reporter virus. We further showed that the reduction in infection correlated with impaired influenza virus trafficking to late endosomes and hence with fusion and entry. To examine whether GBA is required for other enveloped viruses, we compared the results seen with entry mediated by the glycoproteins of Ebola virus, influenza virus, vesicular stomatitis virus (VSV), and measles virus in GBA knockout cells. Entry inhibition was relatively robust for Ebola virus and influenza virus, modest for VSV, and mild for measles virus, suggesting a greater role for viruses that enter cells by fusing with late endosomes. As the virus studies suggested a general role for GBA along the endocytic pathway, we tested that hypothesis and found that trafficking of epidermal growth factor (EGF) to late endosomes and degradation of its receptor were impaired in GBA knockout cells. Collectively, our findings suggest that GBA is critically important for endocytic trafficking of viruses as well as of cellular cargos, including growth factor receptors. Modulation of glucosylceramide levels may therefore represent a novel accompaniment to strategies to antagonize "late-penetrating" viruses, including influenza virus.IMPORTANCE Influenza virus is the pathogen responsible for the second largest pandemic in human history. A better understanding of how influenza virus enters host cells may lead to the development of more-efficacious therapies against emerging strains of the virus. Here we show that the glycosphingolipid metabolizing enzyme glucosylceramidase is required for optimal influenza virus trafficking to late endosomes and for consequent fusion, entry, and infection. We also provide evidence that promotion of influenza virus entry by glucosylceramidase extends to other endosome-entering viruses and is due to a general requirement for this enzyme, and hence for optimal levels of glucosylceramide, for efficient trafficking of endogenous cargos, such as the epidermal growth factor (EGF) receptor, along the endocytic pathway. This work therefore has implications for the basic process of endocytosis as well as for pathogenic processes, including virus entry and Gaucher disease.
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PMID:Glucosylceramidase Maintains Influenza Virus Infection by Regulating Endocytosis. 3091 81