Overexpression of HOXA-AS2 LncRNA in Patients with Gastric Cancer and Its Association with Helicobacter pylori Infection.

PURPOSE: LncRNAs are regulatory factors that play a prominent role in the carcinogenesis processes and cancer cell ability to invade and metastasize. Hence, lncRNAs are considered as the potential diagnostic and therapeutic biomarkers in diverse malignancies. The present study was designed to assess the difference of HOXA-AS2 gene expression levels in cancerous tissues as compared to marginal noncancerous tissues of gastric cancer patients. METHODS: Fifty pairs of cancerous and marginal noncancerous tissue of gastric cancer patients were collected in the present study. Then, RNA extraction and cDNA synthesis were performed for all specimens. The qRT-PCR was carried out to examine the difference of HOXA-AS2 gene expression. Furthermore, the association between HOXA-AS2 expression and the clinicopathological features as well as the function of HOXA-AS2 biomarkers was evaluated. RESULTS: The HOXA-AS2 expression was significantly elevated in cancerous tissues as compared to marginal noncancerous tissues in gastric cancer patients (p < 0.0001). Analysis of gene expression data revealed that there was a significant association between an increased HOXA-AS2 gene expression and clinicopathological features such as tumor size ˃ 5 cm (p = 0.009), lymph node metastasis (p = 0.028), and H. pylori infection (p = 0.011). The results of ROC analysis indicated that HOXA-AS2 with AUC, sensitivity, and specificity of 0.816, 92%, and 70%, respectively, can act as a potential biomarker (CI 95% = 0.7297-0.9023). CONCLUSION: With regard to the overexpression of HOXA-AS2 in gastric cancer tissues, the mentioned gene may serve as an oncogenic lncRNA in gastric cancer patients. Moreover, HOXA-AS2 can act as a potential biomarker in molecular targeted therapies to recognize and treat gastric cancer patients.

Diagnostic and prognostic role of ascitic fluid calprotectin level: six-month outcome findings in cirrhotic patients.

AIM: To assess the role of ascites calprotectin in early detection of SBP in patients with cirrhosis and to investigate its prognostic value in determination of the 6-month outcome. Methods and material: In this cross-sectional study, patients with liver cirrhosis who were consecutively referred to Imam Reza hospital, tertiary referral center in the northwest of Iran, underwent abdominal paracentesis. The samples were collected for measurement of calprotectin, albumin, total protein, WBCs, and PMNs. RESULTS: The mean age of a total of 87 included patients was 56.86 (SD 16.05) years old with over half of the subjects (55.2%) being female. About 28.7% of performed paracenteses tested positive for SBP. Ascitic calprotectin was positively correlated to the PMN counts. Patients with SBP were found to have higher levels of ascites albumin, total protein, and calprotectin. Only 51 individuals survived the 6-month follow-up period and mortality outcomes were significantly related to the levels of aforementioned biochemical markers (p-value <.05). CONCLUSION: Alongside with standard PMN counts, calprotectin measurement in the ascitic fluid could be used as an available test for early diagnosis of SBP. Calprotectin can also serve as a valuable prognostic marker in the evaluation of cirrhotic patients.

Contribution of DNA methylation and EZH2 in SRBC down-regulation in gastric cancer.

Gastric cancer (GC), a high mortality malignancy, is induced by genetic and epigenetic factors. DNA and histone methylation play critical roles in tumor suppressor genes inactivation. SRBC (serum deprivation response factor-related gene product that binds to the c-kinase), suggested as a tumor suppressor gene, participates in apoptosis, tumor chemoresistance and DNA damage response and is repressed in various cancers. Inspecting the mechanisms underlying SRBC suppression is important for cancer treatments. We investigated SRBC promoter DNA methylation status and expression of SRBC and EZH2 histone methyltrasferase in gastric cancer. Also, we surveyed SRBC expression after 5-azacitidine and UNC1999 treatments of AGS cell line. In current work, we used gastric adenocarcinoma tissues, marginal samples and normal gastric biopsies. DNA methylation was detected by Methylation- Specific PCR and mRNA expression was measured by Real-Time PCR. SRBC promoter methylation analysis, showed fully and partial methylated versions that were associated with patient's age (p = 0.001). SRBC expression significantly decreased in GC compare with marginal and normal samples (p-value < 0.001). EZH2 showed remarkable up-regulation in GC than controls and demonstrated a strong inverse correlation with SRBC expression (r = - 0.69). Restoration of SRBC expression was observed after 5-azacitidine and UNC1999 applications with a remarkable increase by combinational treatment. We showed that EZH2 plays role in SRBC silencing in addition to DNA methylation. Our study, suggests that DNA methylation and EZH2 are involved in SRBC silencing and their inhibitors can be considered in cancer treatment investigations to overcome chemoresistance induced by SRBC inactivation.

Overexpression of CFL1 in gastric cancer and the effects of its silencing by siRNA with a nanoparticle delivery system in the gastric cancer cell line.

Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, and metastasis of cancer cells is one of the main features of this illness. The expression levels of the CFL1 gene have been modulated in this pathway. Using small interfering RNA (siRNA) in the treatment of gastric cancer is considered a hopeful gene therapeutic approach. The present study reported the level of CFL1 genes between tumor and margin and healthy tissue of gastric cancer. Also, the features of a cationic nanoparticle with a polymer coating containing polyacrylic acid and polyethyleneimine that were used in the delivery of CFL1 siRNA, were shown. Then the cytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle were evaluated with CFL1siRNA. METHOD: In this study, the CFL1 gene expression was measured in 40 gastric adenocarcinoma, marginal and 15 healthy biopsy samples by a real-time polymerase chain reaction. Physicochemical characteristics, apoptosis, and inhibition of migration of the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated in gastric cancer cells. RESULT: The CFL1 expression was remarkably increased in gastric cancer tissues in comparison with the marginal samples and normal tissues (p < .05) and the biomarker index for CFL1 was obtained as 0.94, then this gene can be probably used as a biomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, the CFL1 expression level of mRNA and migration in AGS cells were remarkably suppressed after transfection. Furthermore, the amount of apoptosis increased (p < .05). CONCLUSION: Our results demonstrated that CFL1 downregulation in AGS cells can interdict cell migration. Finally, our outcomes propose that CFL1 can function as an oncogenic gene in gastric cancer and would be considered as a potential purpose of gene therapy for gastric cancer treatment.

Investigation of the changes in the expression levels of MOZ gene in colorectal cancer tissues.

BACKGROUND: MOZ is one of the most important histone acetyltransferases (HATs) that has an effective role in gene expression. It is an important partner in chromosomal rearrangement that usually occurs in hematological malignancies such as leukemia. Besides these malignancies, its role in solid tumors has been reported. In the present study, we aimed to quantify of MOZ messenger RNA (mRNA) expression in colorectal cancer (CRC) tissues from a northwest population of Iran and consequently to assess the effect of MOZ in CRC. METHODS: Tumorous and adjacent non-tumorous tissues recruited from 26 patients with CRC. mRNA extraction and complementary DNA (cDNA) synthesis were performed from these tissues, at the next step quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) was carried out. Finally, expression levels were statistically analyzed using IBM SPSS Statistics 24.0 software and independent t-test. Statistical significance was considered as P≤0.05. RESULTS: The results showed significantly higher expression of MOZ in the majority of CRC tissues compared to normal colorectal tissues (P=0.048). There were no significant correlations between expression levels of MOZ and clinical parameters of patients (P>0.05). CONCLUSIONS: Our data showed that dysregulation of MOZ is potentially involved in the pathogenesis of CRC and we could suggest that there is a straight relationship between tumor formation and MOZ expression. These results showed possible role of MOZ as a prognostic factor in the said population.

Overexpression of SSH1 in gastric adenocarcinoma and its correlation with clinicopathological features.

BACKGROUND: Gastric adenocarcinoma is known to be the fourth most common cancer type and the second cause of cancer-related deaths. Movement and invasion of cancer cells is one of the major characteristics of the cancer phenotype that various types of network regulate this. Expression levels of slingshot diphosphatase 1 (SSH1) gene has been modulated in this pathway. SSH1 acts as a dephosphorylation and activator of cofilin that this regulating and activating by SSH1 can play a major role in the mobility and migration of the cell. The aim of this study was to compare the expression level of SSH1 genes between tumor and corresponding adjacent non tumor gastric tissues and healthy tissue of gastric adenocarcinoma. METHODS: In this study, mRNA of 40 gastric adenocarcinoma and corresponding adjacent non tumor gastric tissues and 15 healthy biopsy samples was extracted, then after cDNA synthesis, real-time polymerase chain reaction was performed to measure gene expression. RESULTS: According to REST analysis, the relative expression of SSH1 was significantly increased in gastric cancer tissues compared to the corresponding adjacent non tumor gastric tissue samples and normal tissue. Nevertheless, the result revealed no substantial correlation between the expression levels of SSH1 with clinical features. The biomarker index for SSH1 was obtained as 0.89. CONCLUSIONS: The results obtained from investigating SSH1 expression are indicative of significant changes in the expression of this gene in gastric adenocarcinoma. This gene can also be used as a biomarker for gastric cancer.

The Value of miR-299-5p in Diagnosis and Prognosis of Intestinal-Type Gastric Adenocarcinoma.

MicroRNAs (miRNAs) are a class of non-coding RNAs, containing about 22 nucleotides and having a pivotal function in various cellular processes. The oncogenic and tumor suppressor roles of miRNAs have been identified in cancers especially in gastric cancer, which is one of the most prevalent cancers. MiR-299-5p is located in the imprinted Dlk1-Dio3 region in chromosome 14q32. Aberrant expression of miR-299-5p was determined in solid and blood cancers. The current study was performed to assess the expression pattern of miR-299-5p in intestinal-type gastric adenocarcinoma and compare it with the normal adjacent counterparts. The expression level of miR-299-5p was investigated in forty fresh specimens which were obtained from gastric cancer patients during endoscopy. Moreover, the association of aberrant expression of miR-299-5p and clinicopathological features, as well as the susceptibility of miR-299-5p as a tumor marker, was determined. The result of qRT-PCR revealed the downregulation of miR-299-5p in intestinal-type gastric adenocarcinoma compared with adjacent tumor-free tissues (P < 0.001); this misregulation can be used as a tumor marker. Analysis of miR-299-5p misregulation did not reveal a significant correlation with clinical features. The result obtained from the present study revealed the significant downregulation of miR-299-5p in intestinal-type gastric adenocarcinoma which is consistent with previous studies showing miR-299-5p downregulation in other types of cancers. The data obtained from the current study suggest basic information which can be very helpful for future research in the field of diagnosis and treatment of gastric cancer.

Endoscopic retrograde cholangiopancreatography outcome from a single referral center in Iran.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the first choice for diagnostic evaluation of the pancreatic and biliary tree and can be accompanied by a high diagnostic sensitivity and a poor therapeutic outcome. In the current study, we described our experiences in the indications, findings, and technical success of ERCP in a sample of the Iranian population admitted to a referral center in Iran. METHODS: In a retrospective review database-based study, 780 patients (393 males and 387 females; mean age 57.5 years) who had undergone diagnostic and therapeutic ERCP with the primary diagnosis of hepatobiliary disorder between 2006 and 2008 at Taleghani Hospital in Tehran were reviewed. The key data were demographic characteristics, clinical information, laboratory parameters, as well as post-ERCP complications. RESULTS: A history of cholecystectomy was found in about one-third (36.3%) of participants and 80 (10.3%) out of 780 patients had a previous history of biliary stone. A minority (1.4%) of the patients suffered from hepatobiliary carcinomas, and 11 patients had cirrhosis. The most common clinical manifestations in the patients undergoing diagnostic ERCP were icterus (47.3%), weight loss (31.2%), and dark urine (26.9%). Selective biliary cannulation was technically successful in 87.0% of the patients; however, cannulation failed in 13.0%. The most frequent final diagnosis of ERCP was common bile duct stone that was detected in 40.1% of the patients. The ERCP results in 11.0% of the patients were normal. Regarding appropriate treatment, successful stenting was performed in 43 patients (15.2%). Among post-ERCP complications, pancreatitis was the most adverse event with an incidence rate of 3.3%. Other complications including local bleeding, cholangitis and gastrointestinal perforation, rarely occurred. Post-ERCP pancreatitis was reported in 1.8% of men and 3.6% of women (P=0.120). Pancreatitis was more common in women below 70 years than in those who were older than 70 years (3.6% versus 0.5%; OR: 8.216, P=0.015). This might be due to the more functionally active pancreas in younger women than in the older ones. However, other complications were similar in the two age groups. CONCLUSIONS: Based on our experience, ERCP indications, final diagnosis and related complications are comparatively consistent with those reported in other countries. The most common post-ERCP complication is pancreatitis that is more often observed in younger patients.

Clinical and pathological characteristics of colorectal polyps in Iranian population.

BACKGROUND & AIM: Colon polyps are important lesions and a concern because of the potential for colorectal cancer. Colorectal carcinoma is one of the most common causes of cancer-related deaths in Iranian population. The distribution of polyps in the colon may affect the efficacy of a screening modality. The aim of this study was to determine clinical & pathology characteristics of colorectal polyps in Iranian population. MATERIAL & METHODS: In this study is cross sectional survey that 856 polypectomies were done in 716 patients. Anatomical distribution, size and histopathology of polyps were described in 2004 - 2008 in the educational hospital of Taleghani in Tehran. RESULTS: polyps were observed in 437 males and 279 females and gastroenterologists did colonoscopic polypectomy. 3.12 percent of polyps were located in the rectum, 19.6 percent in sigmoid, 24.4 percent in descending colon, 13.9 percent in transverse colon, 29.6 percent were in cecum and ascending colon. 77 (9%) polyps were non-neoplastic and 779 (91%) were neoplastic. Adenomas were present in 727 (85%) cases, of these 411 (56% of adenomas) were left-sided and 316 (44% of adenomas) were right-sided. Carcinoma was observed in 52 cases, of these 18 (34.5%) were left sided and 34 (65.5% of carcinomas) were right sided. Of them 354 were advance polyp (> 1 cm, villous type, high grade dysplasia). 87 (34%) of Advance polyps were in under 50 year patients and 149 (58.6%) were right sided. CONCLUSION: This study has shown that a significant number of adenomas and carcinomas lie proximal to the splenic flexure. Thus, in the absence of left-sided lesions, it is expected that examination of the colon limited to the splenic flexure would miss 44% of such lesions. The increasing right-sided prevalence of these lesions with age suggests that evaluation of the proximal bowel is particularly important in older people. In addition there were higher stages of dysplasia and malignancy in larger polyps.