Mojtaba Saffari

Background and Objective: The platelet-derived growth factor receptor (PDGFR) signaling pathway has a vital function as a regulator of glioma development. PDGFRA alterations have been observed in a variety of cancers and have been important clinical targets for tyrosine kinase inhibitors like Imatinib. The aim of this study was to evaluate the role of ...

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the articular tissue. This study aims to evaluate the expression of microRNA (miR)-146a-5p, miR-24-3p, and miR-125a-5p in the plasma of RA patients and compare them with those of healthy controls to obtain a specific expression profile for earlier diagnosis and assistance in treating patients. This study was performed on 50 RA patients and 50 healthy controls. Five microliters of blood were taken from each patient/control. Plasma RNA was extracted using the Trisol solution. cDNAs were synthesized; using moloney murine leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Real-time PCR was performed using SYBR green kit. The mean expression of miR-146a-5p, miR-24-3p, and miR-125a-5p in the RA group were 8.1±1.9, 6.5±1.2, and 6.8±2.2 and in the healthy group were 4.8±1.6, 3.6±2.2, and 3.4±1.7, respectively. Significant differences were also observed in the mean expression of these three miRNAs in four subgroups of RA patients with different disease activity based on disease activity score 28 (DAS28) (p<0.05). ROC curve analysis showed that miR-146a-5p (AUC=0.8, sensitivity=96%, specificity=86%), miR-24-3p (AUC=0.7, Sensitivity=95%, Specificity=75%) and miR-125a-5p (AUC=0.71, sensitivity=93%, specificity=84%) could be used as suitable biomarkers for RA diagnosis. Increased expressions of miR-146a-5p, miR-24-3p, and miR-125a-5p in RA patients indicate that the miRNAs are involved in disease incidence and progression, and the measurement of their expression can play an essential role in the diagnosis and treatment of the disease.

The glioblastoma multiform has some properties including rapid growth, invasion, treatment resistance, and recurrence. Therefore, new therapies need to be developed that can be approved for using in patients. The previous study showed Arsenic Trioxide inhibits aggressive behavior in glioblastoma cells. Also, (–)-epigallocatechin-3-gallate prevents cellular proliferation, and invasion in multiple glioma cells. Resveratrol decreases cellular proliferation, induces cell death, and impaired the invasiveness of glioma cells. Combination therapy to inhibit cancer cells may have important clinical implications. Therefore, to assess the combination therapy of 2μM Arsenic trioxide, 100μM EGCG, and 100μM Resveratrol, we examined the metabolic activity, colony formation, media pH, cell proliferation, Caspase 3 activity, and gene expression analysis of BCL2, Caspase 3, MMP2, MMP9, CA9, u-PA, u-PAR, and Cathepsin B genes in apoptosis and invasion by both quantitative PCR experiments and Western blot assay. Systems biology tools also were used to obtain, the related network, involved pathways, and identifying the key genes in our selected criteria. The results of the study confirmed that the combined therapy prevents cell proliferation and induces of apoptosis in the Brain tumor cell lines including: U87-MG, A-172, and 1321N1. Furthermore, over-expression of caspase-3 and down-regulation of BCL-2, MMP-2, and MMP-9 confirmed that combination therapy leads to induces apoptosis and decreases invasion. Nevertheless, the lowering of pharmacological doses and improving therapeutic efficacy through combination therapy may provide advantages to treat resistance cancer cells with lower side effects. Finally, the results might suggest new modality for Glioblastoma treatment.

Breast cancer, as the most frequent cancer diagnosed in women worldwide, is affected by different regulatory mechanisms and cellular processes such as micro ...

As an inducer of epithelial-mesenchymal transition (EMT), fibroblast growth factor-10 (FGF-10) has a role in cell proliferation and differentiation in the embryo in addition to invasion and metastasis during carcinogenesis. In this study, we aimed to investigate the FGF-10 gene expression in tumor tissues based on the pathological feature of tumor related to EMT and metastasis. 62 tumors were obtained from 62 colorectal cancer patients during surgery. The pathological characteristics of the patients were carefully collected and classified by Iran National Tumor Bank. To quantify FGF-10 gene expression, RNA extraction, reverse transcription-PCR and real-time PCR were respectively performed. In addition, three colorectal cancer cell lines including LS174T, SW-948 and SW-480 were collected and cultured for further molecular analysis. Consequently, FGF-10 gene expression showed increased expression level in LS174T and SW-948 while it displayed decreased level in SW-480. Considering the tumor samples, we found an upregulation of FGF-10 gene expression in 52.1 % of all tumors in stage III and only in 9.09 % of all tumors in stage I. Also, there were an upregulation of FGF-10 gene expression in 50 % of all positive lymph invasion patients. Besides, FGF-10 gene upregulation was observed in 50 % of all tumors with a size larger than 5 cm (P value < 0.05) and 69 % of all tumors located in the colon (P value < 0.05). To our knowledge, this is the first time that FGF-10 expression is reported based on pathological features of colorectal cancer.

Introduction & Objective: Developmental Dysplasia of the Hip (DDH) is one of the most common congenital skeletal anomalies. Body of evidence suggests that genetic variations in GDF5 are associated with susceptibility to DDH. DDH is a multifactorial disease and its etiology has not been entirely determined. Epigenetic changes such as DNA methylation could be linked to DDH. In this scheme, we hypothesized that changes in GDF5 DNA methylation could predispose a susceptible individual to DDH.Methods: This study consisted of 45 DDH patients and 45 controls with healthy femoral neck cartilage, who underwent hemi‐, or total arthroplasty for the femoral neck fracture. A cartilage sample of 1 cm in diameter and 1 mm in the thickness was obtained for DNA extraction. DNA was extracted and DNA methylation of GDF5 was evaluated by metabisulfite method.Results: Methylation analysis showed that the promoter of GDF5 in cartilage samples from DDH patients was hypermethylated in comparison to healthy controls (p = .001).Conclusion: Our study showed that the methylation status of the GDF5 in patients with DDH is dysregulated. This dysregulation indicates that adjustment in the methylation might modify the expression of this gene. Since this gene plays an essential role in cartilage and bone development, thus reducing its expression can contribute to the pathogenesis of DDH. Further studies are needed to elucidate the role of GDF5 in this disease.

Purpose: This study aims to investigate the expression level of mir-let7b-3p and mir-548, which are involved in PTEN expression in tissue samples of prostate cancer patients versus benign prostate hyperplasia (BPH) and normal adjacent tissue. Materials and Methods: Prostate cancer tissues were obtained from patients after receiving informed consent. Total RNA extraction and cDNA synthesis were performed for determining gene expression. Results: Ten patients were determined to have high Gleason scores (> 7), 36 and seven samples had intermediate Gleason scores (7 >=) and BPH, respectively, and 40 samples were derived from normal adjacent tissue. Downregulation of mir-let7b and upregulation of mir-548 expression significantly correlated with high-risk Gleason scores. Conclusion: The present study showed that miR-let7b and/or mir-548 can be considered as potential targets in prostate cancer therapy.

Aim: miRNAs have been suggested as biomarkers for bladder cancer. We aimed to find a diagnostic panel of miRNAs based on differential expression of miRNAs in urine specimens of patient with bladder cancer compared with control group. Methods: miR-141, miR-10b, miR-34b and miR-103 were selected to assess their expression in urine samples of 66 bladder cancer patients and 53 matched controls using quantitative real time PCR. Results: miR-10b and miR-34b were upregulated in cases compared with controls. The combination of four miRNAs showed a sensitivity of 75% and specificity of 63.5% with a diagnostic power of 72%. Conclusion: Certain miRNAs can be used as biomarkers for early diagnosis of bladder cancer.