ABSTRACT
Background: The Human Epidermal growth factor Receptor-3 [HER-3] is a member of ErbB receptor family and has deficient kinase activity. HER-3 should heterodimerize with other members of ErbB receptor family, especially with HER-2, to transduce downstream signaling pathways. HER-3 co-expresses with other ErbB receptors in different cancers and overexpresses while the oncogenic signaling pathways such as Jak/Stat, MAPK, and PI3K/Akt are activated and promoted. Here, the expression level of HER-3 was evaluated in Iranian gastric adenocarcinoma's patients and the effects of HER-3 knocking down was investigated on cell cycle and cell viability of human gastric adenocarcinoma cell line of MKN45
Methods: In this study, 38 paraffin-embedded surgical adenocarcinoma specimens and their marginal non-tumor tissue samples were collected. Total RNAs were extracted and cDNAs were synthesized. Finally, the expression level of HER-3 was evaluated by real time PCR approach. Moreover, the human adenocarcinoma cell line of MKN45 was transfected with siRNA against HER-3 and the effects of its down-regulation were evaluated using MTT assay and cell-cycle analysis
Results: The data obtained from this study revealed HER-3 is significantly overexpressed in gastric tumors rather than non-tumor marginal tissues. Also, it was found that the expression level of HER-3 is elevated with tumor depth of invasion. Moreover, HER-3 knocking down promotes cell accumulation in G2/M phase of cell cycle and decreases cell viability in MKN45 cells which suggests a potential role for HER-3 in gastric adenocarcinoma tumorigenesis
Conclusion: Taken together, these results emphasize the importance of HER-3 receptor in diagnosis and prognosis of gastric adenocarcinoma
ABSTRACT
Background and Aims: Prostate cancer [PCa] is one of the most common cancers among men in Iran. Since changes in the regulation of proto-oncogenes expression are the main causes of most human cancers, including PCa, evaluating the expression of marker genes can be helpful for early diagnosis of cancer and better understanding of its etiology. The present study compared c-Myc expression level in prostatic adenocarcinoma and benign prostatic hyperplasia [BPH]
Material and Methods: Paraffin-embedded prostatic tissues from patients with prostate adenocarcinoma [n=38] and BPH [n=38] were selected. The samples were included only if the patients underwent radical prostatectomy and had no history of hormone therapy, chemotherapy, or radiotherapy. After RNA extraction and cDNA synthesis, c-Myc expression in the samples was compared using SYBR green-based real-time polymerase chain reaction
Results: Significantly higher c-Myc mRNA expression was observed in adenocarcinoma samples than in BPH group [p=0.001]. No significant correlation was observed between c-Myc expression and Gleason Score [p>0.05]. There were no significant correlations between c-Myc expression and prostate-specific antigen levels and age [p>0.05]
Conclusions: The c-Myc mRNA expression increased in the PCa samples compared with the BPH group. It seems that c-Myc expression can be introduced as a prognostic marker for determination of the invasive potential of tumor cells. Further tests and studies conducted with larger sample sizes may help to use this marker in differentiating malignant from benign samples
ABSTRACT
PURPOSE: This study aimed to analyze G3BP1 and VEZT expression profiles in patients with gastric cancer, and examine the possible relationship between the expressions of each gene and clinicopathological factors. MATERIALS AND METHODS: Expression of these genes in formalin-fixed paraffin embedded (FFPE) tissues, collected from 40 patients with gastric cancer and 40 healthy controls, was analyzed. Differences in gene expression among patient and normal samples were identified using the GraphPad Prism 5 software. For the analysis of real-time polymerase chain reaction products, GelQuantNET software was used. RESULTS: Our findings demonstrated that both VEZT and G3BP1 mRNA expression levels were downregulated in gastric cancer samples compared with those in the normal controls. No significant relationship was found between the expression of these genes and gender (P-value, 0.4835 vs. 0.6350), but there were significant changes associated with age (P-value, 0.0004 vs. 0.0001) and stage of disease (P-value, 0.0019 vs. 0.0001). In addition, there was a direct relationship between VEZT gene expression and metastasis (P-value, 0.0462), in contrast to G3BP1 that did not demonstrate any significant correlation (P-value, 0.1833). CONCLUSIONS: The results suggest that expression profiling of VEZT and G3BP1 can be used for diagnosis of gastric cancer, and specifically, VEZT gene could be considered as a biomarker for the detection of gastric cancer progression.
Subject(s)
Humans , Diagnosis , Gene Expression , Neoplasm Metastasis , Paraffin , Real-Time Polymerase Chain Reaction , RNA, Messenger , Stomach NeoplasmsABSTRACT
Background: Type II diabetes is known as one of the most important, prevalent, and expensive diseases of mankind. Late diagnosis and subsequent delayed initiation of treatment or surveillance of patients create a variety of problems for affected individuals. This has raised increasing concerns for public health authorities throughout the world. In the current study, we aimed to find a new approach for early identification of high-risk individuals at initial months of their life. This allows us to take preventive measures as early as possible
Materials and Methods: In our study, 102 infants - from one to six months - were selected and placed in two case and control groups. The case group contained 52 babies with at least one of their parents identified as a type II diabetic patient. The control group comprised 50 babies with no family history of type II diabetes in paternal and maternal first-degree relatives. Afterwards, the expression level of insulin gene was analyzed in white blood cells of both groups. Information related to infants - referred to outpatient and inpatient wards of three main pediatric hospitals placed in Tehran - and their parents were collected through questionnaires within a two-year period. The study inclusion criteria for infants were confirmed type II diabetes in at least one of their parents, the absence of any metabolic disorder, and the absence of any disturbing vital signs. After drawing 2 ml of babies' peripheral blood, total RNA of white blood cells [WBC] was extracted, and used for cDNA synthesis. Real-Time PCR was then applied to quantitatively evaluate the expression levels of insulin gene. The results of Real-Time PCR were statistically analyzed by non-parametric tests of Mann-Whitney and Kruskal-Wallis
Results: The expression of insulin gene was observed in white blood cells of all samples. However, there was a significant difference in expression levels between case and control groups [p<0.05]. There was a statistically significant difference in mean levels of gene expression among babies with diabetic mother, and healthy groups [RQ=0.5, P-value=0.002], but this value wasn't significant for babies with diabetic father [RQ=0.78, P>0.05]
Conclusion: Numerous genes contribute to the development of diabetes and novel disease-causing genes are increasingly being discovered. Identification of disease-prone individuals through examining merely one underlying gene is complicated and challenging. Interestingly, all of these abnormally functioning genes finally manifest themselves in the altered expression levels of insulin gene. The expression status of insulin gene in WBCs could be suggested as a useful approach for identification of individuals at high risk for developing diabetes. This paves the way for taking appropriate measures at infancy period in order to prevent the disease as well as inhibit its various side effects in the following years of patient's life
ABSTRACT
Patients with diabetes mellitus type II suffer from hyperglycemia because they are not able to use the insulin that they produce, often due to inadequate function of insulin receptors. There are some evidences that this deficiency is inherited in a dominant autosomal manner and leads to the malfunction of the pancreatic beta cells resulting in insulin excretion disorders. In this study, we sought to identify mutations in the insulin receptor [INSR] gene, which can cause insulin resistance in type II diabetic patients. DNA was extracted from peripheral blood cells of the patients [n = 128] diagnosed with type II diabetes. All 22 exons of the INSR gene of the patients were analyzed for mutations running PCR, conformation-sensitive gel electrophoresis and DNA sequencing, consecutively. Approximately 26% of the patients had genetic mutations; however, most of them were not reported. These mutations include exon 2 [His171Asn, Ile172Ser, Cys196Ser and Ser210Arg], exon 3 [Gly227Asp and Gly232Ser], exon 8 [Thr543Ser], exon 9 [a heterozygote was observed with no change in phenylalanine at position 669], exon 13 [two heterozygotes: Arg890Pro with Asn865 remaining unchanged], exon 14 [Ala906Gly and Pro918Trp with Arg902 unchanged], exon 17 [Val1086Glu] and exon 19 [His1157Gln with Thr1172 unchanged]. The lack of similar mutation records in literature and genetic data banks may suggest a geographic pattern for these INSR gene variants in our population