Gastroenterology and Hepatology From Bed to Bench
Year:2017 | Volume:10 | Issue:1|Papers Count:14

Introduction Celiac disease (CD) was initially a real enigma. There were many questions about what immunogenetics markers could influence the immune response (1). Immunogenetic studies provided important contributions to improve the understanding of critical pathogenetic factors at molecular levels (DQ2, DQ8) (2). An important discovery was the recognition of more precise serological markers for CD, specifically anti-endomysial and anti-tissue transglutaminase antibodies leading to an exploration of their increasingly important role in clinical diagnosis of CD (3). Our aim is to explore new and old challenges with unanswered questions in CD diagnosis.

Colorectal cancer (CRC) is mostly due to a series of genetic alterations that are being greatly under the influence of the environmental factors. These changes, mutational or epigenetic modifications at transcriptional forefront and/or post-transcriptional effects via miRNAs, include inactivation and the conversion of proto-oncogene to oncogenes, and/or inactivation of tumor suppressor genes (TSG). Here, a thorough review was carried out on the role of TSGs with the focus on the APC as the master regulator, mutated genes and mal-/dysfunctional pathways that lead to one type of hereditary form of the CRC; namely familial adenomatous polyposis (FAP). This review provides a venue towards defining candidate genes that can be used as new PCR-based markers for early diagnosis of FAP. In addition to diagnosis, defining the modes of genetic alterations will open door towards genome editing to either suppress the disease or reduce its progression during the course of action.

Aim: Our aim was to determine the association between TGF-β 1 polymorphisms at position-509 C>T (rs1800469) and +915 G>C (rs1800471) and pancreatic cancer susceptibility in Iranian population. Background: Ninety percent of pancreatic cancer patients have less than 5-year overall survival and approximately 50% of cases were diagnosed with metastasis in the time of admission. Previous evidences have demonstrated the strong association between TGF-β 1 variations and cancer susceptibility so far. Methods: A total of 78 patients with pancreatic cancer and 94 healthy controls were enrolled in this case control study from 2007-2012. Genomic DNA was isolated from peripheral blood samples according to phenol chloroform extraction. The genotypes of TGF-β 1 rs rs1800469 and rs1800471 were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The mean age of cases and the control group were 64. 50 ± 13. 718 and 40. 12 ± 16. 001, respectively. For polymorphism-509 C>T, the frequency of TT genotype were 31 (33. 0), CT, 47(50) and CC, 16 (17) in control and 19 (24. 4), 45 (57. 7) and 14 (17. 9) in cases respectively. In position +915 G>C, the frequency of GG genotype was 84 (89. 4) and GC, 10 (10. 6) in control and 71 (91. 0) and 7 (9) in cases, respectively. We did not observe any significant differences in the genotype and allele frequencies of the TGF-β 1-509 C>T (rs1800469) and codon +915 G>C (rs1800471) between the two study groups (P>0. 05). Conclusion: we found that TGF-β 1 gene polymorphisms rs1800469 and rs1800471 might not play a role in pancreatic cancer susceptibility in Iranian population.

Aim: Since interactome analysis of diseases can provide candidate biomarker panel related to the diseases, in this research, proteinprotein interaction (PPI) network analysis is used to introduce the involved crucial proteins in Gastric adenocarcinoma (GA). Background: Gastric adenocarcinoma (GA) is the most common type of stomach cancer. There is no efficient diagnostic molecular method for GA. Method: Applying Cytoscape software 3. 4. 0 and String Database, the PPI network was constructed for 200 genes. Based on centrality parameters, the critical nodes were screened. Gene ontology of the key proteins for pathway analysis and molecular function processing were done and the highlighted pathways and activities were discussed. Results: Among 200 initial genes, 141 genes were included in a main connected network. Seven crucial proteins, including tumor protein p53, epidermal growth factor receptor, albumin, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), v-akt murine thymoma viral oncogene homolog 1, v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) and catenin (cadherin-associated protein), beta 1, 88kDa, and Myogenic differentiation 1, were introduced as key nodes of the network. These identified proteins are mostly involved in pathways and activities related to cancer. Conclusion: In conclusion, the finding is corresponding to the significant roles of these introduced proteins in GA disease. This protein panel may be a useful probe in the management of GA.

Aim: The present study investigated the anti-tumor activity of Imatinib mesylate through modulation of NM23 gene expression in human hepatocellular carcinoma (HepG2) cell line. Background: Hepatocellular carcinoma (HCC) is considered to be the third leading cause of cancer related death worldwide. Down regulation of NM23, a metastasis suppressor gene, has been associated with several types of malignant cancer. Recently, effects of Imatinib mesylate, a first member of tyrosine kinases inhibitors, were indicated in research and treatment of different malignant tumors. Methods: Cell viability was quantitated by MTT assay after HepG2 cells exposure to Imatinib mesylate at various concentrations of 0, 1. 56, 3. 125, 6. 25, 12. 5, 25, 50μ M for 24 hours. Also, quantitative real time PCR technique was applied for the detection of NM23 gene expression in HepG2 cell line. Results: There was a dose dependent increase in the cytotoxicity effect of imatinib. The real time PCR results demonstrated that inhibitory effect of Imatinib mesylate on viability via up regulation of NM23 gene expression compared to GAPDH gene (internal control gene) in cancer cells. Conclusion: According to our findings, imatinib can modulate metastasis by enhancing Nm23 gene expression in human hepatocellular carcinoma (HepG2) cell line.

Background: Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. Therefore, polymorphisms in genes encoding the cytokines, which are responsible for regulation of the immune response, can affect the course and outcome of the infection. The IFN-γ +874 T/A polymorphism affects the expression of IFN-γ , which has been shown to be crucial to HBV clearance. Aim: This study aimed to investigate the association of IFN-γ +874 (T/A) polymorphism with susceptibility to chronic HBV infection in the Syrian population. Patients and Methods: In this case-control study, 140 samples were collected (70 healthy individuals, 70 chronic HBV patients), and genomic DNA was isolated. Sequencing and ARMS-PCR were performed to genotype the IFN-γ +874 T/A polymorphism. Results: Results of this study showed an association between IFN-γ +874 T/A polymorphism and the susceptibility to chronic HBV infection (P < 0. 05). In addition, results showed that the AA genotype increased the risk of chronicity (OR = 3. 05, 95% CI = 1. 35 – 6. 89), whereas the AT and TT genotypes reduced the risk of chronicity (OR = 0. 33, 95% CI = 0. 150 – 0. 753). Conclusion: Results of this study conclude that the IFN-γ +874 T/A polymorphism may be associated with the chronic HBV infection, according to the genetic model AA vs. AT&TT.

Background: Hepatitis-B e-antigen (HBeAg)-negative is common in Iran, is progressive with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings. Aim: To evaluate the association between biochemical, virologic and histologic features in patients with HBeAg-negative chronic hepatitis B (CHB). Materials and methods: HBeAg-negative CHB patients referring to two university hospitals during two years were enrolled. Alcohol consumption, liver mass, fatty liver and positive results of Anti HDV, Anti HCV or Anti HIV were excluded. The relationship between viral loads, liver enzymes (old and new cutoffs) and histopathological features was analyzed using descriptive and analytic statistical methods. Results: A total of 150 HBeAg-negative CHB (males=110, mean age=38. 44± 11. 34 years) were assessed. ALT had a significant relation with the logarithm of serum HBV-DNA (P<0. 0001), grade and stage on liver biopsy (P<0. 001, P=0. 034, respectively). Serum viral load, AST and ALT were independent predictors of histological grade, age was the only independent predictor of the stage of liver fibrosis. There was a significant relationship between serum ALT and stage of liver fibrosis (P<0. 0001) when new cutoff values for ALT were considered. We found that age had a significant relation with histological grade but it showed a reverse relation with ALT levels (P=0. 009). Conclusions: In HBeAg-negative CHB, AST had a better prediction for liver necrosis and inflammation. Age could be an independent predictor for liver fibrosis. New cutoff values for ALT had superiority over conventional values to identify higher risk of liver fibrosis.

Aim: The aim of the present study was to evaluate the different doses of Butyric acid (BA) and Arsenic (As) in liver mitochondria oxidative stress and pancreatic islet insulin secretion of male mouse. Background: BA is found in many foods and As as a toxic metal is present in drinking water. They can induce oxidative stress in tissues. Materials and Methods: In this experimental study, Liver mitochondria were isolated by administration of the different centrifugation method and pancreatic islets were isolated by collagenase method. Mitochondria were incubated by BA (35, 75, 150, 300 μ M) and As (20, 50, 100, 200 μ M) as the islets were incubated by BA (250, 500, 1000, 1500 μ M) and As (50, 100, 200 μ M) for 1 hour. At the end of the experiment, mitochondrial viability and membrane potential, ROS, MDA, GSH and islets insulin secretion were measured by their specific methods. Results: BA and As administration increased mitochondrial levels of ROS, MDA and decreased GSH and pancreatic islet insulin secretion in a dose dependent manner (p<0. 05). The doses of BA 75μ M and As 100μ M have been revealed the most mitochondria toxic concentrations. Also, the doses of 1000μ M for BA and 100μ M for As were considered as reducing concentrations for islets insulin secretion. Additionally, co administration of them intensified more these effects Conclusion: Alone or in combination administration of BA and As induced oxidative stress in liver mitochondria and decreased insulin secretion of pancreatic islets.

Aim: The aim of this study was to assess the association between survival of patients with colorectal cancer and prognostic factors in a competing risk parametric model using Weibull distribution. Background: The prognosis of colorectal cancer is relatively good in terms of survival time. In many prognostic studies, patients may be exposed to several types of competing events. These different causes of death are called competing risks. Methods: Data was recorded from 372 patients with colorectal cancer who registered in the Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences (Tehran, Iran) from 2004 to 2015 in a retrospective study. Analysis was performed using competing risks model and Weibull distribution. Software used for data analysis was R, and significance level was regarded as 0. 05. Results: The result indicated that, at the end of follow-up, 111 (29. 8%) deaths were from colorectal cancer and 14 (3. 8%) deaths were due to other diseases. The average body mass index (BMI) was 24. 61(SD 3. 98). The mean survival time for a patient in 372 was 62. 05(SD 48. 78) month with median equals to 48 months. According to competing-risks method, only stageIII ( HR, 1. 69; 95% CI, 1. 246-2. 315 ), stageIV( HR, 4. 51; 95% CI, 2. 91-6. 99 ) and BMI( HR, 0. 96; 95% CI, 0. 96-0. 975) have a significant efect on patient’ s survival time. Conclusion: This study indicated pathologic stage(III, IV) and BMI as the prognosis, using a Weibull model with competing risks analysis, while other models without the competing events lead to significant predictors which may be due to over-estimation.

Aim: To survey person centered survival rate in population based screening program by an intelligent clinical decision support system. Background: Colorectal cancer is the most common malignancy and major cause of morbidity and mortality throughout the world. Colorectal cancer is the sixth leading cause of cancer death in Iran. In this survey, we used cosine similarity as data mining technique and intelligent system for estimating survival of at risk groups in the screening plan. Patients and methods: In the first step, we determined minimum data set (MDS). MDS was approved by experts and reviewing literatures. In the second step, MDS were coded by python language and matched with cosine similarity formula. Finally, survival rate by percent was illustrated in the user interface of national intelligent system. The national intelligent system was designed in PyCharm environment. Results: Main data elements of intelligent system consist demographic information, age, referral type, risk group, recommendation and survival rate. Minimum data set related to survival comprise of clinical status, past medical history and socio-demographic information. Information of the covered population as a comprehensive database was connected to intelligent system and survival rate estimated for each patient. Mean range of survival of HNPCC patients and FAP patients were respectively 77. 7% and 75. 1%. Also, the mean range of the survival rate and other calculations have changed with the entry of new patients in the CRC registry by real-time. conclusion: National intelligent system monitors the entire of risk group and reports survival rates by electronic guidelines and data mining technique and also operates according to the clinical process. This web base software has a critical role in the estimation survival rate in order to health care planning.

An 81-year-old male presented with multiple episode of severe PR bleeding over 2 days. CTA done prior to catheter angiography that enabled successful intervention. This case emphasises the importance of CTA prior to catheter angiography in acute LGIB

Lithophagia is a type of pica that might be resulted from Iron Deficiency Anemia (IDA)which is the frequent presenting signs of Celiac Disease (CD). A 5-year-old child with a two year history of the lithophagia with a, refractory IDA, abdominal distention and constipation. The child did not grow well and had failure to thrive. With suspicion to CD, TTg IgA level was measured and due to an incearse of TTg IgA level the patients were undergone esophagogastrodeudonoscpy and jejunal biopsy. The biopsy showed severe villous atrophy and an increase in limphoplasma cells. Biopsy confirmed diagnosis of CD and glutten free diet was initiated finally. Six months after diagnosis and commencing the gluten free diet, the lithophagia and constipation in patient eradicated completely. IDA and failure to thrive were improved And the level of TTg IgA was reached to the normal The case demonstrated the relationship between lithophagia and CD in anemia. Therefore, in the same cases such as our case should be considered CD as the most important causes of lithophagia.

Pheochromocytomas are rare and often sporadic tumours of catecholamine-secreting chromaffin cells, usually present within the adrenal medulla, but also may occur elsewhere. A 45-year-old female was referred by her general practitioner with a 5-year history of increasingly frequent episodes of cyclical diarrhoea, vomiting, abdominal pain and intermittent palpitations. Contrast CT Abdomen/Pelvis revealed a 36x33x46 mm mass in the aorto caval region of her retro-peritoneum, just above the bifurcation. On the basis of her symptoms, CT findings and an elevated plasma metanephrine level of 2314pmol/L (normal range 80 – 510pmol/L), it was at this point a likely diagnosis of a Phaeochromocytoma was made. The retroperitoneal mass was successfully resected, and the histology confirmed a Phaeochromocytoma. Her symptoms rapidly improved and she made a good recovery. This unusual case highlights some of the dilemmas that arise when investigating patients with chronic and recurrent diarrhoea and vomiting.

This prospective, single center study examined the occurrence of synchronous Secondary Primary Tumours (SPTs) of the oesophagus in patients with a new diagnosis of head and neck squamous cell carcinoma (HNSCC). The idea of ‘ field cancerization’ – where similarly exposed areas to a primary cancer are at higher risk of developing carcinoma – is theorized for the cause of this common phenomenon. The findings of other studies put the incidence of synchronous SPTs in HNSCC as high as 36%...