Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD44 is a transmembrane glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain and to contain at least one ankyrin-binding site in its cytoplasmic domain. In this study we have examined CD44 expression in a mouse fibroblast cell line transfected with the pl85(neu) oncogene cDNA. The results of RT-PCR and Southern blot analyses reveal that CD44s (CD44 standard form) transcript is expressed in both pl85(neu)-transfected cells and untransfected cells. Using surface iodination, anti-CD44 immunoprecipitation and immuno-binding assays, we have found that the number of CD44s molecules expressed on the surface of pl85(neu)-transfected cells are at least 4.5-fold higher than those detected on untransfected cells. Overexpression of surface CD44s in pl85(neu)-transfected cells results in a dramatic enhancement of HA-mediated cell adhesion. Scatchard plot analysis indicates that CD44s in pl85(neu) transfected cells binds directly and specifically to ankyrin. The binding affinity between CD44s and ankyrin in p185(neu)-transfected cells approximately 0.19 nM) appears to be somewhat higher than that found in the untransfected cells (K(p) approximately 0.30 nM). Double immunofluorescence staining and confocal microscopic analyses indicate that HA induces the HA receptor (i.e. CD44s) to form adhesion plaque-like structures, and causes an accumulation of intracellular ankyrin directly underneath HA receptor (CD44s)-adhesion plaque-like structures in pl85(neu)-transfected cells (but not in untransfected cells). These findings suggest that overexpression of CD44s and up-regulation of CD44s-ankyrin interaction by pl85(neu) oncogene may be one of the pre-requisite steps in regulating tumor cell behavior.
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PMID:Overexpression of CD44 in pl85(neu)-transfected NIH3T3 cells promotes an up-regulation of hyaluronic acid-mediated membrane-cytoskeleton interaction and cell adhesion. 864 70

Astrocytes form functional networks that participate in active signaling in which external stimuli are generated and amplified in many of the same ways as in neurons. Gap junctions between astrocytes offer the structural avenue by which the electrical and metabolic signals are propagated from one cell to another. Little is known about the trafficking, assembly, and degradation mechanisms of the major astrocytic gap junction protein connexin43. We have studied a glial cell line transfected with the C-erbB2/neu oncogene (neu+), finding severe interruption of gap junctional communication after stable transfection. Evidence from Western blotting and phosphorylation studies showed that the processing of connexin43 to its higher phosphorylated isoforms is disturbed. Confocal laser imaging indicates that the major deficit in the neu+ cells is attributable to a lack in plaque assembly of connexin43. Because the neu+ cells also lack N-CAM proteins and because work from others has indicated a close relationship between communication competence and constitutive CAM expression, our data suggest that expression of C-erbB2/neu oncogene alters cell-cell association via CAM proteins, which thereby affects gap junction plaque assembly and appropriate phosphorylation of connexin43.
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PMID:C-erbB2/neu transfection induces gap junctional communication incompetence in glial cells. 869 42

This study determined the effect of Ad-E1A gene therapy in vivo. TC71 cells (2 x 10(6)) injected subcutaneously into nude mice resulted in tumor development (1-3 mm) 6 days later. Animals were then treated with Ad-E1A or Ad-beta-gal (5 x 10(9) plaque-forming units) by intratumoral injection twice weekly for 2 weeks. Animals received 8 mg/kg VP-16 given by intraperitoneal injection daily for 5 days following the first week of treatment with Ad-E1A or Ad-beta-gal. Control animals received no therapy or VP-16 only after tumor cells were injected. When tumors exceeded 2 x 2 cm, the mice were sacrificed and the tumors underwent histologic and immunohistochemical analysis. Tumors from mice treated with Ad-E1A plus VP-16 were 9.6-fold smaller than those treated with VP-16 alone and 6.3-fold smaller than those treated with Ad-E1A alone. HER2/neu p185 protein expression decreased in all tumors that received Ad-E1A therapy. TUNEL fluorescence staining revealed more apoptosis in the tumors from animals treated with Ad-E1A plus VP-16 than in those from animals treated with Ad-E1A alone, Ad-beta-gal plus VP-16, or VP-16 alone. These data demonstrated that Ad-E1A gene therapy down-regulated HER2/neu expression, increased tumor cell apoptosis induced by VP-16, and enhanced tumor cell sensitivity to VP-16. Ad-E1A may have potential in the treatment of relapsed drug-resistant Ewing's sarcoma.
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PMID:Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma to VP-16. 1196 63

Enterovirus 71 (EV71) is a neurotrophic virus that causes seasonal morbidity and mortality in children throughout the world with increasing frequency in recent years. Because of the lack of an effective antiviral agent, primary prevention, including the development of effective vaccines, is a top priority in terms of control strategies. Poliovirus vaccine technology, both live attenuated and inactivated, killed virus vaccines, can be adopted for use with EV71 because of their relatedness. In this study, we have characterized a laboratory-adapted EV71 strain, YN3-4a, which exhibits different characteristics from those of its parent isolate, neu, in having a rapid growth rate in Vero cells, a larger plaque size, and a lower LD(50) in newborn mice. The YN3-4a can be produced at a high viral titer of up to 10(10) tissue culture infective dose (TCID(50)) when grown in Vero cells, an approved substrate for virus vaccine production. Mouse antiserum raised against YN3-4a can neutralize a broad range of strains of EV71 isolated at different times from a variety of geographic regions. On passage in Vero cells, YN3-4a remained genetically and phenotypically stable. Many of the above-described features, such as high viral yield, strong immunogenicity, broad-based antigenic coverage, and passage stability, are desirable features in a prototype virus for the development of an inactivated viral vaccine.
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PMID:Characterization of a Vero cell-adapted virulent strain of enterovirus 71 suitable for use as a vaccine candidate. 1205 3

In order to use adenovirus (Ad) type 5 (Ad5) for cancer gene therapy, Ad needs to be de-targeted from its native receptors and re-targeted to a tumor antigen. A limiting factor for this has been to find a ligand that (i) binds a relevant target, (ii) is able to fold correctly in the reducing environment of the cytoplasm and (iii) when incorporated at an optimal position on the virion results in a virus with a low physical particle to plaque-forming units ratio to diminish the viral load to be administered to a future patient. Here, we present a solution to these problems by producing a genetically re-targeted Ad with a tandem repeat of the HER2/neu reactive Affibody molecule (ZH) in the HI-loop of a Coxsackie B virus and Ad receptor (CAR) binding ablated fiber genetically modified to contain sequences for flexible linkers between the ZH and the knob sequences. ZH is an Affibody molecule specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) that is overexpressed in inter alia breast and ovarian carcinomas. The virus presented here exhibits near wild-type growth characteristics, infects cells via HER2/neu instead of CAR and represents an important step toward the development of genetically re-targeted adenoviruses with clinical relevance.
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PMID:Adenovirus 5 vector genetically re-targeted by an Affibody molecule with specificity for tumor antigen HER2/neu. 1727 81

Extramammary Paget's disease (EMPD) is a rare malignant neoplasm with a predilection for the apocrine-rich anogenital skin and less commonly for the axilla. The tumor rarely occurs in non-apocrine bearing regions where it is referred to as ectopic EMPD. Here, we report a case of a patient that presented with a poorly circumscribed, erythematous plaque with patchy alopecia on the scalp. Histology showed pagetoid infiltration of the epidermis by atypical single and nested cells with abundant amphophilic cytoplasm with nuclear hyperchromasia, extending along the adnexae. Immunohistochemistry showed that the tumor cells stained positively for mucicarmine, periodic acid schiff, cytokeratin-7, polyclonal carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein, androgen receptor and Her-2-neu; and negatively for S-100, HMB-45, CDX-2, thyroid transcription factor-1, estrogen receptor and progesterone receptor, thus, establishing the diagnosis of ectopic EMPD. Subsequent workup showed no underlying malignancy. To our knowledge, we report the second case, and the first in the English literature, of an ectopic EMPD involving the scalp without any associated malignancy.
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PMID:Extramammary Paget's disease presenting as alopecia neoplastica. 1958 7

We reported a 52-year-old woman with an apocrine gland carcinoma of the mammary skin concomitant with pagetoid phenomenon. She had a 23-year history of a small nodular lesion on the lower left part of her right breast with a 1-year history of the pigmented plaque spreading peripherally around the nodule. Our diagnosis revealed that the nodule was an apocrine gland carcinoma and the intraepidermal neoplastic cells with pagetoid spread in the pigmented plaque were derived from the apocrine gland carcinoma. No Paget's cells were detected in the right nipple, and no tumor cells were observed in the sentinel lymph node and underlying mammary gland tissue. We also investigated the immunohistochemical changes in this case. They showed that both intraepidermal neoplastic cells with pagetoid spread and tumor cells of the apocrine gland carcinoma were positive with cytokeratin-7 and human epidermal growth factor receptor-2 (HER-2)/neu overexpression. The results of the present study conclude that the intraepithelial spread of tumor cells in the mammary skin distant from the nipple occurred as a pagetoid phenomenon, and that HER-2 may have a key role in pagetoid phenomenon of an underlying apocrine gland carcinoma, as well as in mammary Paget's disease.
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PMID:Apocrine gland carcinoma of the mammary skin concomitant with pagetoid phenomenon. 2050 5

Distinguishing primary cutaneous adnexal carcinoma from metastatic carcinoma of unknown primary can be a diagnostic challenge due to the frequent overlap of histologic and immunohistochemical features. A 58-year-old man presented with a tender, indurated plaque on axillary skin. Biopsy revealed infiltrating atypical cells throughout the dermis, without connection to the epidermis. Tumor cells had a histiocytoid appearance and displayed mild pleomorphism. The tumor was discohesive and had areas with a single file pattern. Signet ring cells were also present. Cells were reactive with CK7, CK5/6, p63, GATA3, GCDFP-15 and Her 2-neu. Additional studies were negative, including TTF-1, CDX2, E-cadherin, mammaglobin, estrogen receptor and progesterone receptor. Thorough clinical and radiologic evaluation failed to identify an occult primary extracutaneous malignancy; however, regional lymphadenopathy, widespread osteoblastic lesions and multiple subcentimeter liver hypodensities were noted. Considering the clinical and histopathologic features, the diagnosis of primary cutaneous histiocytoid carcinoma with distant metastasis was favored.
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PMID:Primary cutaneous histiocytoid carcinoma with distant metastasis. 2800 Mar 3