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

Platinum-containing regimens are very effective in the primary treatment of ovarian cancer. However, upon subsequent treatment most tumors develop multidrug resistance. The clinical application of biological response modifiers like interferon gamma (IFN gamma) in advanced ovarian cancer is therefore of increasing interest. Permanent ovarian cancer cell lines are suitable for investigating the mode of action and the potential clinical effectiveness of such response modifiers. IFN gamma is known to modulate many cellular functions. In this study it was compared for its antiproliferative and antigen-modulatory activity on the expression of tumor-associated (CA-125, HMFG, CEA) and major histocompatibility complex (MHC) class I and II antigens as well as of the epidermal growth factor (EGF) receptor on 20 newly established human ovarian carcinoma cell lines. IFN gamma in concentrations of 10, 50 and 100 U/ml was used to study its antigen-modulatory effect, and at additional 1 U/ml and 1000 U/ml to assess its antiproliferative effect on the cells. The cells were incubated with IFN for 4 days. Two cell lines showed strong antiproliferative activity even at minimal doses (up to 50 U/ml). Intermediate growth inhibition between 34% and 84% was observed in 15 cell lines with higher doses. Three lines were resistant to IFN gamma. Independent of the antiproliferative effect, IFN gamma enhanced the expression of MHC class I and MHC class II in nearly all cell lines. Upregulation was also observed for most of the tumor-associated antigens (TAA) and EGF receptor expression. A down-regulation was noticed but rarely. The fact that IFN gamma showed an antiproliferative activity on the majority of the cell lines is of clinical relevance. The in vitro modulation of cell-surface determinants by IFN gamma warrants special attention. The enhanced expression of TAA and MHC antigens can improve immunogenicity of the tumor cells and may explain the therapeutic effects observed under IFN therapy in ovarian cancer. By contrast, enhanced expression of the EGF receptor, often associated with poor patient survival rates, may be an undesirable side-effect of IFN therapy.
 ...
PMID:Effects of interferon gamma on the proliferation and modulation of cell-surface structures of human ovarian carcinoma cell lines. 827 Jun 4

The inability to identify relevant markers for presymptomatic screening in early stage or "preinvasive" ovarian cancer has plagued investigators and clinicians facing the problems of early detection. The characteristic late stage of disease at initial presentation has hindered our understanding of the biologic progression and stepwise molecular alterations that result in ovarian carcinoma. To date, most screening studies have focused on identifying early anatomic changes using ultrasound or fluctuations in serum biomarkers such as CA-125. These screening methodologies have proven inadequate in both sensitivity and specificity for early stage ovarian cancer detection. Molecular analysis of ovarian carcinomas has revealed alterations in oncogenes and tumor suppressor genes associated with these tumors. The HER-2/neu oncogene, a member of the epidermal growth factor family, is amplified or overexpressed in approximately 25-30% of ovarian carcinomas. Significant data substantiate an important role for HER-2/neu in the pathophysiology of ovarian cancer. While potentially an attractive surrogate endpoint biomarker (SEB), serum HER-2/neu levels have not proven to be a useful screening modality. In response to the urgent need for improved early detection for ovarian cancer, our current research efforts include differential hybridization studies between normal and malignant ovarian epithelium to define potentially unique ovarian cancer antigens which may ultimately have utility; defining physical alterations that occur in malignant ovarian tissues using implanted telemetry systems; studies using positron emission tomography to detect changes in glucose metabolism between normal and malignant ovarian tissues; and screening studies using a 3-dimensional ultrasound unit to improve the accuracy of this technique in recognizing early neoplastic changes. By taking diverse approaches to tackle this problem, an improved understanding of ovarian carcinogenesis should translate into the identification of appropriate SEBs for early detection.
 ...
PMID:Screening for ovarian cancer: what are the optimal surrogate endpoints for clinical trials? 874 1

Clear cell carcinoma of the gynecologic tract has been defined in terms of its clinical and histologic features; however, its immunophenotypic profile has not been fully characterized. Seventeen cases of primary clear cell carcinoma from various sites within the female genital tract (11 ovary, 5 uterus, 1 vagina) were analyzed by immunohistochemistry. These tumors were assessed for the expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), low and high molecular weight cytokeratin, (CAM5.2 and 34 beta E12, respectively), carcinoembryonic antigen (CEA), Leu-M1, vimentin, estrogen receptor (ER), progesterone receptor (PR), bcl-2, p53, HER-2/neu, and CA-125. The characteristic immunoprofile for all sites was positivity for CK7, CAM5.2, 34 beta E12, CEA, Leu-M1, vimentin, bcl-2, p53, and CA-125; variably positivity for ER and HER-2/neu; and negativity for CK20 and PR. For comparison, two cases of urologic clear cell carcinoma (1 bladder, 1 urethra) were also studied, and their profile was found to be similar to the gynecologic cases. Aside from minor differences, clear cell carcinoma appears to have the same immunophenotype regardless of whether it originates in the endometrium, ovary, or genitourinary tract. Much of its profile is similar to other gynecologic adenocarcinomas, but some of the markers studied may be useful in the differential diagnosis of this tumor.
 ...
PMID:Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract. 1144 1

Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of endometrial cancer with features similar to high-grade ovarian cancer. Patients tend to be elderly, thin, have a high grade tumor with extensive extrauterine disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistochemistry in <25% of ovarian cancers and 20-30% of breast cancers, and <10% of endometrial cancer. There are prognostic and therapeutic implications associated with the overexpression of this transmembrane protein. Herceptin, a humanized murine monoclonal antibody directed against the extracellular domain of the HER-2/neu protein, is being used to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and 19 patients had specimens available for evaluation. We performed immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of 19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five patients had advanced disease at diagnosis. Two of these patients were subsequently treated with Herceptin; one with complete response and one with stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be beneficial for a select group of patients with UPSC. We are continuing to evaluate samples for HER-2/neu over expression by fluorescence in situ hybridization (FISH).
 ...
PMID:HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications. 1700 89