Browsing by Author "Pavlov, V."
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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 Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence(BioMed Central, 2013) Alaiyan, B.; Ilyayev, N.; Stojadinovic, A.; Izadjoo, M.; Roistacher, M.; Pavlov, V.; Tzivin, V.; Halle, D.; Pan, H.; Trink, B.; Gure, A. O.; Nissan, A.Background: The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis.Methods: Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH).Results: Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods.Conclusion: CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process. © 2013 Alaiyan et al.; licensee BioMed Central Ltd.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.