Browsing by Author "Grinbaum, R."
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Item Open Access Colon cancer associated transcript-1 (CCAT1) expression in adenocarcinoma of the stomach(Ivyspring International Publisher, 2015) Mizrahi, I.; Mazeh, H.; Grinbaum, R.; Beglaibter, N.; Wilschanski, M.; Pavlov, V.; Adileh, M.; Stojadinovic, A.; Avital, I.; Gure, A. O.; Halle, D.; Nissan, A.Background: Long non-coding RNAs (lncRNAs) have been shown to have functional roles in cancer biology and are dys-regulated in many tumors. Colon Cancer Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be significantly up-regulated in colon cancer. The aim of this study is to determine expression levels of CCAT1 in gastric carcinoma (GC). Methods: Tissue samples were obtained from patients undergoing resection for gastric carcinoma (n=19). For each patient, tumor tissue and normal appearing gastric mucosa were taken. Normal gastric tissues obtained from morbidly obese patients, undergoing laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric carcinoma cell line (AGS) served as positive control. RNA was extracted from all tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR). Results: Low expression of CCAT1 was identified in normal gastric mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ) = 1.95±0.4]. AGS human gastric carcinoma cell line showed an elevated level of CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8 fold higher in GC samples than in samples taken from the negative control group (RQ=21.1±5 vs. RQ=1.95±0.4, respectively, p<0.001). Interestingly, CCAT1 expression was significantly overexpressed in adjacent normal tissues when compared to the negative control group (RQ = 15.25±2 vs. RQ=1.95±0.4, respectively, p<0.001). Tissues obtained from recurrent GC cases showed the highest expression levels (RQ = 88.8±31; p<0.001). Expression levels increased with tumor stage (T4- 36.4±15, T3- 16.1±6, T2- 4.7±1), however this did not reach statistical significance (p=0.2). There was no difference in CCAT1 expression between intestinal and diffuse type GC (RQ=22.4±7 vs. 22.4±16, respectively, p=0.9). Within the normal gastric tissue samples, no significant difference in CCAT1 expression was observed in helicobacter pylori negative and positive patients (RQ= 2.4±0.9 vs. 0.93±0.2, respectively, p=0.13). Conclusion: CCAT1 is up-regulated in gastric cancer, and may serve as a potential bio-marker for early detection and surveillance.Item Open Access Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues(Wiley, 2012) Nissan, A.; Stojadinovic, A.; Rosenbaum, S. M.; Halle, D.; Grinbaum, R.; Roistacher, M.; Bochem, A.; Dayanc, B. E.; Ritter, G.; Gomceli, I.; Bostanci, E. B.; Akoglu, M.; Chen, Y. T.; Old, L. J.; Gure, A. O.Early detection of colorectal cancer (CRC) is currently based on fecal occult blood testing (FOBT) and colonoscopy, both which can significantly reduce CRC-related mortality. However, FOBT has low-sensitivity and specificity, whereas colonoscopy is labor- and cost-intensive. Therefore, the discovery of novel biomarkers that can be used for improved CRC screening, diagnosis, staging and as targets for novel therapies is of utmost importance. To identify novel CRC biomarkers we utilized representational difference analysis (RDA) and characterized a colon cancer associated transcript (CCAT1), demonstrating consistently strong expression in adenocarcinoma of the colon, while being largely undetectable in normal human tissues (p < 000.1). CCAT1 levels in CRC are on average 235-fold higher than those found in normal mucosa. Importantly, CCAT1 is strongly expressed in tissues representing the early phase of tumorigenesis: in adenomatous polyps and in tumor-proximal colonic epithelium, as well as in later stages of the disease (liver metastasis, for example). In CRC-associated lymph nodes, CCAT1 overexpression is detectable in all H&E positive, and 40.0% of H&E and immunohistochemistry negative lymph nodes, suggesting very high sensitivity. CCAT1 is also overexpressed in 40.0% of peripheral blood samples of patients with CRC but not in healthy controls. CCAT1 is therefore a highly specific and readily detectable marker for CRC and tumor-associated tissues. Copyright © 2011 UICC.Item Open Access Early detection and staging of colorectal cancer using a panel of micro RNAs(OMICS, 2018) Shapira, R.; Ilyayev, N.; Attali, R.; Westrich, G.; Halle, D.; Speter, C.; Stavropoulos, A. V.; Roistacher, M.; Pavlov, V.; Grinbaum, R.; Protic, P.; Güre, Ali O.; Bilchik, A. J.; Stojadinovic, A.; Mitrani-Rosenbaum, S.; Nissan, A.Purpose: To improve lymph node (LN) staging in patients with colon cancer (CC). The present study describes the selection of CC-specific miRNAs and assesses their utility as a micro metastases detection assay. Methods: 30 miRNAs have been selected from a microarray assay and 16 miRNAs from database mining for their specific upregulation in colon cancer tissues as compared to normal adjacent tissues. Differential expression was validated by RT-qPCR in a larger cohort of samples (n=20) and compared to normal lymphatic tissues (n=6) and normal peripheral blood lymphocytes (PBLs, n=14). The selected miRNA panel was then used for the screening of 84 lymph nodes (LN) obtained from colon cancer patients (n=20) Results: After validation, a panel of 8 miRNAs was found to be significantly upregulated in CC compared to normal adjacent tissues and to normal lymphatic tissues: miR-96, miR-183, miR-194, miR-200a, miR-200b, miR200c, miR-203 and miR-429. A total of 84 LNs were analysed: 12 LN metastases were detected by H&E, 18 by CK staining whereas 32 were detected by the CC-specific miRNA analysis. This represents an increase of 40% in the detection rate. Conclusion: This study demonstrated the ability of a CC-specific 8 miRNA panel in detecting micro metastases in CC patients.