5-Azacytidine Enhancing Expression of E-cadherin in Adenocarcinoma Cell Line

Introduction: In this study, we assessed the expression of E-cadherin in HT29 cell line treated with 5-Azacytidine and colorectal cancer patient in an Iranian population. E-cadherin expression promotes metastasis and prognosis of colorectal cancer (CRC). 5-Azacytidine, a DNA methyl transferase inhibitor, is a clinically used epigenetic drug for treatment of cancer including colorectal cancer, leading to genes activation involved in tumor suppression, especially E-cadherin. Materials and Methods: HT29 cell line treated with 5-Azacitidine and 40 polyps, 20 tumors and 40 adjacent normal tissues samples were enrolled in this study. Using the real-time PCR method, the expression levels of E-cadherin were examined in treated cell line and colorectal cancer tissue. Results: This study proves that 5-Azacytidine induces over expression of E-cadherin in adenocarcinoma cell line, while the expression levels of E-cadherin were not different in tumor and polyp than adjacent normal tissue. Conclusion: To conclude, 5-Azacytidine induces re-expression of E-cadherin in adenocarcinoma cell line. Thus, 5-Azacytidine as demethylation drug activated tumor suppressor gene as E-cadherin

The Effects of Conditioned Medium from Bone Marrow-derived Mesenchymal Stem Cells on EMT Markers

Abstract Introduction: Epithelial-Mesenchymal Transition in colorectal cancer cell is a critical process in which cells lose their epithelial properties and obtain mesenchymal characteristics, resulting in tumor cells and metastasis. This study attempted to work on the effects of conditioned medium from bone marrow-derived mesenchymal stem cells on EMT markers. Materials and Methods: In this study, HT29 was used  which is the colorectal cancer cell line. Cells were treated for 72 hours with BMSC-CM in order to induce EMT in HT29. The Real-Time PCR was used for evaluating EMT markers such as E-cadherin- β-catenin -vimentin-and transcription factors. Results: Inducing EMT in colorectal cancer cells caused morphological changes. It was manifested that E-cadherin is downregulated after induction of EMT with treated BMSC-CM. On the other hand, there were a significant increase in β-catenin, Vimentin, Snail and ZEB1 expression. Conclusion: Understanding the molecular basis of tumor metastasis is critical for colorectal cancer treatment. Findings demonstrated morphological alterations in consequence MSCs-CM activates induction of EMT. This process affects EMT markers of E-cadherina, Vimentin, β-Catenin and transcription factors of Snail and ZEB1. This model helps knowing cancer and metastasis pathway and also could be used in drug screening procedures

Association of miR-200a and miR-205 Expression with Epithelial-Mesenchymal Transition in Colorectal Cancer Cells

Abstract Introduction: MicroRNAs play a critical role in EMT regulation through tightly regulating the transcription factors. EMT (Epithelial-Mesenchymal Transition) in the colorectal cancer cell (CRC) is a highly controlled mechanism, contributing to the development of progressive cancer. Throughout this research, miR-200a/205 was focused as a component implicated throughout regulating the EMT process in colorectal cancer cells. In this sense, the induction of the EMT process was made using colorectal cancer cell lines. Materials and Methods: The mRNA levels of E-cadherin, Vimentin, β-catenin, Zeb1, and Snail were determined using real time-PCR for characterization of the EMT process. True real time-PCR was conducted for evaluating the alteration amount of microRNAs. Results: The findings of this study verified the in-vitro EMT model being developed. The in vitro analysis revealed a negative correlation between the Zeb1 and Snail miR-200a and miR205 (P=0.001) (P=0.0001). The results of miR-200a and miR205 are regulated down in vitro. Conclusion: miR-200a and miR205 may be used as candidates in further research to prevent colorectal cancer's invasive properties via the EMT process

Radiation Therapy in Patients With Brain Cancer: Post-proteomics Interpretation

Introduction: Radiation Therapy (RT) as a common method for cancer treatment could conclude in some side effects. Molecular investigation is one of the approaches that could assist in decrypting the molecular mechanisms of this incident. For this aim, protein-protein interaction network analysis as a complementary study of proteome is applied to explore the RT effect on brain cancer effect after the early stage of exposure prior to skin lesion appears.Methods: Cytoscape 3.7.2 and its plug-ins analyzed the network of DEPs in the treatment condition and the centrality and pathway enrichments were conducted by the use of NetworkAnalyzer and ClueGO+CluePedia.Results:  A network of 15 DEPs indicated that six nodes are key players in the network stability and SERPINC1 and F5 are from the query proteins. Pathways of post-translational protein phosphorylation, Platelet degranulation, and Complement and coagulation cascades are the most highlighted ones for the central nodes that could be affected in radiation therapy.Conclusion: The central proteins of the network of early stage treatments could have additional importance in the mechanisms of radiotherapy response prior to skin lesions. These candidates worth precise attention for this type of therapy after approving by validation studies

Can Giardia Infection Impair the Diagnostic Level of Fecal Calprotectin in Patients with Inflammatory Bowel Disease? A Case Report

Inflammatory bowel disease (IBD) is attributed to complex conditions of gastrointestinal tract that is frequently reported all over the world. Fecal calprotectin evaluation is described as a primary tool to screen IBD patients. There are reports showing the confounding role of some microbial agents in diagnostic levels of calprotectin. A 32-yr-old woman with symptoms like IBD/IBS (irritable bowel syndrome); admitted to IBD Clinic of Behbood Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Jan 2017 for evaluation of the level of fecal calprotectin. In spite of high level of calprotectin, trophozoite of Giardia intestinalis was observed in direct examination of stool sample. Microbial pathogens can lead to false elevation of fecal calprotectin and misdiagnosis of gastrointestinal patients suspected to IBD

Detailed analysis of total colectomy on health-related quality of life in adult patients with ulcerative colitis

The aim of this study was to explore the quality of life (QoL) in a group of patients who had an intractable disease on medical therapy including biologics and underwent surgery

Microbiota Alterations and Their Association with Oncogenomic Changes in Pancreatic Cancer Patients

Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.Peer reviewe

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

Pancreatic cancer (PC) is an aggressive malignancy with a dismal prognosis. To improve patient survival, the development of screening methods for early diagnosis is pivotal. Oncogenomic alterations present in tumor tissue are a suitable target for non-invasive screening efforts, as they can be detected in tumor-derived cells, cell-free nucleic acids, and extracellular vesicles, which are present in several body fluids. Since stool is an easily accessible source, which enables convenient and cost-effective sampling, it could be utilized for the screening of these traces. Herein, we explore the various oncogenomic changes that have been detected in PC tissue, such as chromosomal aberrations, mutations in driver genes, epigenetic alterations, and differentially expressed non-coding RNA. In addition, we briefly look into the role of altered gut microbiota in PC and their possible associations with oncogenomic changes. We also review the findings of genomic alterations in stool of PC patients, and the potentials and challenges of their future use for the development of stool screening tools, including the possible combination of genomic and microbiota markers.Peer reviewe

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

Pancreatic cancer (PC) is an aggressive malignancy with a dismal prognosis. To improve patient survival, the development of screening methods for early diagnosis is pivotal. Oncogenomic alterations present in tumor tissue are a suitable target for non-invasive screening efforts, as they can be detected in tumor-derived cells, cell-free nucleic acids, and extracellular vesicles, which are present in several body fluids. Since stool is an easily accessible source, which enables convenient and cost-effective sampling, it could be utilized for the screening of these traces. Herein, we explore the various oncogenomic changes that have been detected in PC tissue, such as chromosomal aberrations, mutations in driver genes, epigenetic alterations, and differentially expressed non-coding RNA. In addition, we briefly look into the role of altered gut microbiota in PC and their possible associations with oncogenomic changes. We also review the findings of genomic alterations in stool of PC patients, and the potentials and challenges of their future use for the development of stool screening tools, including the possible combination of genomic and microbiota markers.Peer reviewe

DNA methylation biomarkers in colorectal cancer: Clinical applications for precision medicine

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide that is attributed to gradual long-term accumulation of both genetic and epigenetic changes. To reduce the mortality rate of CRC and to improve treatment efficacy, it will be important to develop accurate noninvasive diagnostic tests for screening, acute and personalized diagnosis. Epigenetic changes such as DNA methylation play an important role in the development and progression of CRC. Over the last decade, a panel of DNA methylation markers has been reported showing a high accuracy and reproducibility in various semi-invasive or noninvasive biosamples. Research to obtain comprehensive panels of markers allowing a highly sensitive and differentiating diagnosis of CRC is ongoing. Moreover, the epigenetic alterations for cancer therapy, as a precision medicine strategy will increase their therapeutic potential over time. Here, we discuss the current state of DNA methylation-based biomarkers and their impact on CRC diagnosis. We emphasize the need to further identify and stratify methylation-biomarkers and to develop robust and effective detection methods that are applicable for a routine clinical setting of CRC diagnostics particularly at the early stage of the disease