Epistatic interaction between adiponectin and survivin gene polymorphisms in endometrial carcinoma

Adiponectin appears to play an important role in the development and progression of several obesity-related malignancies. Also, overexpression of survivin, an inhibitor of apoptosis protein, is associated with increased risk of cancers. The aim of this study was to investigate the association between two polymorphisms in the adiponectin gene and endometrial cancer (EC) risk. We also investigated whether epistasis between surviving and adiponectin gene polymorphisms are associated with EC risk in an Iranian population.The samples comprised formalin-fixed, paraffin-embedded tissue sections obtained from the archive of the pathology department, Imam-Khomeini Hospital and Firouzgar hospital. After DNA extraction the genotyping was performed using PCR-RFLP technique.Single nucleotide polymorphisms (SNPs) in adiponectin (rs1063539, rs2241766) and survivin (rs9904341) gene were evaluated in the study. The increased frequency of ADIPOQ rs1063539C allele (CC. +. CG genotype) was associated with decreased EC risk OR: 0.39(0.17-0.90). Survivin rs9904341C allele (CC. +. CG genotype) was associated with increased EC risk crude OR: 2.75(1.27-5.95), adjusted OR: 2.93(1.27-6.76). We observed an epistatic interaction between survivin rs9904341 CC. +. CG genotype and ADIPOQ rs1063539 GG genotype increasing the risk of EC compared to those with other genotypes OR: 4.86(1.88-12.54), P=0.001.Our findings indicate that adiponectin might have a modulatory effect on survivin role and function in EC, which requires further investigation. © 2014 Elsevier GmbH

Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas

Neuropilins (NRP) are cell surface receptors for VEGF and SEMA3 family members. The role of NRP in neurons and endothelial cells has been investigated, but the expression and role of NRP in epithelial cells is much less clear. Herein, the expression and localization of neuropilin 1 (NRP1) was investigated in human and mouse skin and squamous cell carcinomas (SCC). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did colocalize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or EGF-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity

iPSC-based modeling of RAG2 severe combined immunodeficiency reveals multiple T cell developmental arrests

RAG2 severe combined immune deficiency (RAG2-SCID) is a lethal disorder caused by the absence of functional T and B cells due to a differentiation block. Here, we generated induced pluripotent stem cells (iPSCs) from a RAG2-SCID patient to study the nature of the T cell developmental blockade. We observed a strongly reduced capacity to differentiate at every investigated stage of T cell development, from early CD7(-)CD5(-) to CD4(+)CD8(+). The impaired differentiation was accompanied by an increase in CD7(-)CD56(+)CD33(+) natural killer (NK) cell-like cells. T cell receptor D rearrangements were completely absent in RAG2SCID cells, whereas the rare T cell receptor B rearrangements were likely the result of illegitimate rearrangements. Repair of RAG2 restored the capacity to induce T cell receptor rearrangements, normalized T cell development, and corrected the NK cell-like phenotype. In conclusion, we succeeded in generating an iPSC-based RAG2-SCID model, which enabled the identification of previously unrecognized disorder-related T cell developmental roadblocks

iPSC-Based Modeling of RAG2 Severe Combined Immunodeficiency Reveals Multiple T Cell Developmental Arrests

RAG2 severe combined immune deficiency (RAG2-SCID) is a lethal disorder caused by the absence of functional T and B cells due to a differentiation block. Here, we generated induced pluripotent stem cells (iPSCs) from a RAG2-SCID patient to study the nature of the T cell developmental blockade. We observed a strongly reduced capacity to differentiate at every investigated stage of T cell development, from early CD7−CD5− to CD4+CD8+. The impaired differentiation was accompanied by an increase in CD7−CD56+CD33+ natural killer (NK) cell-like cells. T cell receptor D rearrangements were completely absent in RAG2SCID cells, whereas the rare T cell receptor B rearrangements were likely the result of illegitimate rearrangements. Repair of RAG2 restored the capacity to induce T cell receptor rearrangements, normalized T cell development, and corrected the NK cell-like phenotype. In conclusion, we succeeded in generating an iPSC-based RAG2-SCID model, which enabled the identification of previously unrecognized disorder-related T cell developmental roadblocks.In this article, Mikkers

Computational Cancer Biology: An Evolutionary Perspective

ISSN:1553-734XISSN:1553-735

Diagnosis of Prostate Cancer, from Conventional Methods Towards the New Promising CTCs

Prostate cancer is the second common cancer in men. Unluckily, as the result of the indolence of this cancer in its early stages, timely diagnosis of the disease is very difficult. Hence, in the case of this malignancy, health management and mass monitoring of the population is difficult for health organizations. Because of the incompetence of the conventional diagnostic techniques, many researches are trying to find novel biomarkers in order to develop preventive intervention, screening and targeted therapy. Circulating Tumor Cells (CTCs) are new biomarkers originating from primary and/or metastatic tumors, and circulate in the bloodstream. Molecular properties of these new biomarkers provide valuable information about the status of the tumor and can be useful in selection of an appropriate therapy. So far lots of methods have been developed for separating CTCs, such as microfluidics technology. Despite of the recent achievements, current methods suffer from several limitations which hinder effective isolation of all subpopulation of CTCs. Thus, finding an ideal method for separating all subsets of CTSs, is still unmet. Herein, conventional diagnostic methods which are used for detection of prostate cancer are introduced and necessities of new diagnostic techniques specially, does based on CTCs are discussed. This review shows that new emerging techniques and promising biomarkers like CTCs could be effectively applied for early detection of prostate cancer and increase the chance of the successful treatment

K-Ras 4A Transcript variant is up-regulated in eutopic endometrium of endometriosis patients during proliferative phase of menstrual cycle

Aims: K-Ras transcripts comprise two main isoforms: K-Ras 4A and K-Ras 4B, which act differently. The expression of both isoforms was reported in many human tissues. However, K-Ras 4B was the major expressed transcript variant. An increased expression of K-Ras 4B mRNA was reported in eutopic endometrium of endometriosis patients. In this way, we aimed to study the expression of K-Ras 4A transcript in eutopic endometrium related to endometriosis. Methods: Employing exon4-flanking primers, K-Ras isoforms were simultaneously amplified in a RT-PCR reaction. Quantitative real-time PCR was performed using GAPDH as an internal control. K-Ras 4A transcript expression in eutopic endometrium was analyzed by ��CT method. Results: We identified existence of both of K-Ras 4A and K-Ras 4B in eutopic endometrium of patients and controls. Quantitative real-time analysis demonstrated that K-Ras 4A expression was 2.7-fold higher in endometriosis than non-endometriosis eutopic samples. Interestingly, this overexpression mainly occurs through the proliferative phase of menstrual cycle. Conclusion: The findings bring to light the eminent role of K-Ras 4A in endometriosis. This splice variant which is known for promoting apoptosis could be an effective factor in balance between proliferation and death of eutopic endometrial cells. © 2014, Springer-Verlag Berlin Heidelberg

Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case�control study

Endometriosis is a polygenic and multifactorial gynecology situation which might be associated with angiogenesis. In the current study we assess the role of vascular endothelial growth factor (VEGF) � 2578 A/C, and + 936 C/T polymorphisms in susceptibility to endometriosis and checking the expression of VEGF mRNA in eutopic tissue of endometrium with and without endometriosis. The study was comprised of 300 patients who underwent laparascopic or laparotomy surgery with 100 cases who had confirmed histological diagnosis of endometriosis, and 200 controls with no histological diagnosis of disease. The genotyping of VEGF polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR�RFLP) technique and the gene expression in tissue was determined using Real-Time PCR assay. There was no important difference of allele distribution of the � 2578 A/C (P = 0.7) and + 936 C/T (P = 0.5) polymorphisms among endometriosis cases and controls. Study of VEGF expression during the menstrual cycle, showed that endometrial tissue in cases group expressed more VEGF mRNA at the secretory phase compared to the proliferative phase (P = 0.03). Our results suggest that � 2578 A/C and + 936 C/T polymorphisms of VEGF did not seem to have impact on endometriosis predisposition in our study population. Also we did not find any link between VEGF mRNA expression and risk of endometriosis. © 2019, Springer Nature B.V

Association of pulp stones with coronary artery stenosis

Background: Dental pulp stones are discrete calcifications in the pulp chamber which are often seen in deciduous and permanent teeth. It has been hypothesised that atherosclerosis can be associated with their development. Objective: To determine whether a higher prevalence of dental pulp stones is correlated with coronary artery stenosis. Clinical setting: Sixty-one patients aged 20-55 years referred to Afshar Heart Center for invasive coronary angiography were invited to undergo panoramic dental radiography. The panoramic radiographs were independently examined for the presence of pulp stones. Results: Pulp stones were present in 82% (31/38) of patients with at least one clinically significant coronary artery stenosis and in 48% (11/23) of patients with normal coronary angiography. They were present in 13% of the teeth in the former group and in 5% of the teeth in the latter. The findings show a statistically significant association between coronary artery stenosis and presence of pulp stones (odds ratio 4.83, 95% confidence interval 1.5-15.4). Conclusion: Coronary artery stenosis and dental pulp calcification are significantly associated. Dental radiography has the potential to be used as a rapid screening method for the early detection of coronary artery stenosis