Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel tumor-associated antigen, RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is expressed at a high frequency in human uterine and ovarian cancer cells as well as in other mammalian cancer cells. We investigated a relationship between RCAS1 expression and clinicopathological features in gastric cancer. Immunohistochemically, RCAS1 was detected in 98.4% of gastric carcinomas. However, its expression was also observed in non-cancerous gastric epithelial cells including gastric adenomas (100%), gastric ulcers (66.7%) and normal gastric epithelia (100%). Striking difference was observed in the pattern of RCAS1 expression between benign and malignant cells. In cases of normal gastric mucosae, gastric ulcers and gastric adenomas, RCAS1 was localized only in the perinuclear region of the mucosal epithelial cells (PN pattern), while, in most of gastric cancers (83.9%), it was detected diffusely in the cytoplasm and cell membranes of the tumor cells (DC pattern). In semi-quantitative RT-PCR analysis, RCAS1 mRNA levels in gastric adenocarcinoma tissues were significantly higher than those in non-neoplastic tissues (p=0.038). The PN pattern of RCAS1 expression was more frequently observed in well differentiated adenocarcinoma (25%) than in moderately differentiated adenocarcinoma (0%) (p=0.01). In addition, it is noteworthy that DC pattern of RCAS1 expression was more frequently recognized in carcinomas which invaded beyond the submucosa (100%) compared to intramucosal carcinoma (67.7%) (p=0.0026). These findings suggest that altered intracellular distribution of RCAS1 is strictly associated with tumor progression of gastric cancer and is a useful marker for the diagnosis and prognosis in gastric cancer.
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PMID:Aberrant intracellular localization of RCAS1 is associated with tumor progression of gastric cancer. 1156 43

Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERalpha. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERalpha were evaluated by RT-PCR in 22 cases. The expression for EBAG9 and ERalpha was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P=0.0402) and advanced disease (P=0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P=0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (P<0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERalpha mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERalpha expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.
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PMID:Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer. 1516 21

A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and array-based serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations.
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PMID:Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays. 1642 57

Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with advanced disease of various malignancies including ovarian cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its clinical significance and biologic function in ovarian cancer patients are unclear. Here, we evaluated serum RCAS1 concentrations to clarify its clinical significance and biologic activity in ovarian cancer. Via ELISA, we measured serum RCAS1 concentrations in samples from 75 healthy blood donors and 97 patients, 36 with ovarian benign tumor and 61 with ovarian cancer. We correlated via statistical means the RCAS1 values with patients' clinicopathologic variables. We assessed inhibition of growth of K562 cells, which express the putative RCAS1 receptor, via WST-1 assay of serum samples to clarify RCAS1's biologic activity. Ovarian cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors and ovarian tumor patients (P<0.05). RCAS1 level was significantly different according to histologic subtype for both ovarian tumor and cancer patients (P=0.0266 and 0.0074, respectively). RCAS1 values were also significantly associated with response to treatment (P<0.001). The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1 (P=0.0074). RCAS1 may be a biomarker of ovarian cancer by virtue of its ability to predict results of treatment and inhibit immune cell growth.
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PMID:Clinical significance of RCAS1 as a biomarker of ovarian cancer. 1727 43

Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression.
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PMID:Analysis of the expression of human tumor antigens in ovarian cancer tissues. 2016 40

The PI3 kinase/Akt pathway is commonly deregulated in human cancers, functioning in such processes as proliferation, glucose metabolism, survival and motility. We have previously described a novel function for one of the Akt isoforms (Akt3) in primary endothelial cells: the control of VEGF-induced mitochondrial biogenesis. We sought to determine if Akt3 played a similar role in carcinoma cells. Because the PI3 kinase/Akt pathway has been strongly implicated as a key regulator in ovarian carcinoma, we tested the role of Akt3 in this tumor type. Silencing of Akt3 by shRNA did not cause an overt reduction in mitochondrial gene expression in a series of PTEN positive ovarian cancer cells. Rather, we find that blockade of Akt3, results in smaller, less vascularized tumors in a xenograft mouse model that is correlated with a reduction in VEGF expression. We find that blockade of Akt3, but not Akt1, results in a reduction in VEGF secretion and retention of VEGF protein in the endoplasmic reticulum (ER). The reduction in secretion under conditions of Akt3 blockade is, at least in part, due to the down regulation of the resident golgi protein and reported tumor cell marker, RCAS1. Conversely, over-expression of Akt3 results in an increase in RCAS1 expression and in VEGF secretion. Silencing of RCAS1 using siRNA inhibits VEGF secretion. These findings suggest an important role for Akt3 in the regulation of RCAS1 and VEGF secretion in ovarian cancer cells.
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PMID:Akt3 controls vascular endothelial growth factor secretion and angiogenesis in ovarian cancer cells. 2135 Oct 97

RCAS1 is involved in generating the suppressive profile of the tumor microenvironment that helps cancer cells evade immune surveillance. The status of the cells surrounding the cancer nest may affect both the progression of the cancer and the development of metastases. In cases of ovarian cancer, a large number of patients do not respond to the applied therapy. The patient's response to the applied therapy is directly linked to the status of the tumor microenvironment and the intensity of its suppressive profile. We analyzed the immunoreactivity of RCAS1 on the cells present in the ovarian cancer microenvironment in patients with the disease; these cells included macrophages and carcinoma-associated fibroblasts. Later we analyzed the immunoreactivity levels within these cells, taking into consideration the clinical stage of the cancer and the therapeutic strategy applied, such as the number of chemotherapy regiments, primary cytoreductive surgery, or the presence of advanced ascites. In the patients who did not respond to the therapy we observed significantly higher immunoreactivity levels of RCAS1 within the cancer nest than in those patients who did respond; moreover, in the non-responsive patients we found RCAS1 within both macrophages and carcinoma-associated fibroblasts. RCAS1 staining may provide information about the intensity of the immuno-suppressive microenvironment profile found in cases of ovarian cancer and its intensity may directly relate to the clinical outcome of the disease.
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PMID:The analysis of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) immunoreactivity within the microenvironment of the ovarian cancer lesion relative to the applied therapeutic strategy. 2184 2