Characterization and prognostic value of mutations in exons 5 and 6 of the p53 gene in patients with colorectal cancers in central Iran

Background/Aims: We aimed to investigate the relation-ships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. Methods: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. Results: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p<0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p<0.01). Conclusions: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease

Including cognitive aspects in multiple criteria decision analysis

"First Online: 21 December 2016"Many Multiple Criteria Decision Analysis (MCDA) methods have been proposed over the last decades. Some of the most known methods share some similarities in the way they are used and configured. However, we live in a time of change and nowadays the decision-making process (especially when done in group) is even more demanding and dynamic. In this work, we propose a Multiple Criteria Decision Analysis method that includes cognitive aspects (Cognitive Analytic Process). By taking advantage of aspects such as expertise level, credibility and behaviour style of the decision-makers, we propose a method that relates these aspects with problem configurations (alternatives and criteria preferences) done by each decision-maker. In this work, we evaluated the Cognitive Analytic Process (CAP) in terms of configuration costs and the capability to enhance the quality of the decision. We have used the satisfaction level as a metric to compare our method with other known MCDA methods in literature (Utility function, AHP and TOPSIS). Our method proved to be capable to achieve higher satisfaction levels compared to other MCDA methods, especially when the decision suggested by CAP is different from the one proposed by those methods.This work was supported by COMPETE Programme (operational programme for competitiveness) within project POCI-01-0145-FEDER-007043, by National Funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within the Projects UID/CEC/00319/2013, UID/EEA/00760/2013, and the João Carneiro PhD grant with the reference SFRH/BD/89697/2012.info:eu-repo/semantics/publishedVersio

The effect of the marker expression HMWCK in Benign prostatic hyperplasia (BPH) and Adenocarcinoma by immunohidtochemistery an histology methods

AbstractBackground and purpose: The effect of the marker expression high molecular weight cytokeratin ) HMWCK ( in Benign prostatic hyperplasia (BPH) and adenocarcinoma prostate. There were conventional reported about rate expression HMWCK in adenocarcinoma prostate The purpose of this studied was to determine expression of the marker HMWCK with histopathological parameters in BPH and adnocarcinoma in prostatic by immunohistochemistry methods. Materials and Methods: This descriptive analytical research was conducted on 79 patients admitted to Hospital in Isfahan Iran. Samples were fixed in formalin and tissue processing and stained by hematoxilin and eosin adenocarcinoma samples were classified with Gleason pattern ( score) method by two pathologist. The effect of over expression in marker expression HMWCK was done after diagnosis by two expert(blind). The obtained data were analyzed using chi-square test.Results: Out of the 79 specimens 43 samples were BPH and 36 samples were adenocarcinoma . in 40 samples with diagnosis BPH were observed of the marker HMWCK and 3 samples were negative. Out of 36 samples with diagnosis adenocarcinoma 35 them over expression marker of the HMWCK were negative but one samples was positive. . The over specimens malignancy were in higher Gleason score There was significant relationships between type samples (BPH and adenocarcinoma) with over expression of the marker HMWCK

The role of ethanol on the anticonvulsant effect of valproic acid and cortical microvascular changes after epileptogenesis in mice

Abstract There have been conflicting reports regarding the role of ethanol in seizure.Another effect of ethanol is vascular damage in cerebral tissue. This study investigates the influence of ethanol on antiepileptic efficacy of valproic acid (VPA) and cerebral microvascular structure. In this study, four groups of mice (25–30 g) received pentylenetetrazole (PTZ) i.p. (37 mg/kg) every other day. Different groups of animals received an injection of saline, ethanol (1 g/kg),VPA (100 mg/kg), or VPA and ethanol 30 min before PTZ. Animals in groups 5 and 6 received only ethanol and saline, respectively. After recording seizure parameters, the animals were sacrificed under deep anesthesia and the brains of the animals were removed and fixed, thereafter coronal sections were prepared from cerebral cortex. Then, the cerebral microvessels were counted in microscopic sections after hematoxylin–eosin staining. Ethanol injection (1 g/kg) for 7 days decreased stage 4 duration and increased latency to the onset of stage 1 and stage 4 of seizure (p\0.001). Concomitant injection ofVPA(5 min before ethanol) and ethanol had significantly stronger anticonvulsant effects than VPA alone (p\0.001). Furthermore, the findings showed that not only the cerebral microvessels increased significantly in ethanol group compared with saline group (p\0.05), but also there were morphological changes in vascular endothelium in ethanol group. The obtained results show that shortterm ethanol administration has anticonvulsant effects along with VPA, and enhances the anticonvulsant effects of VPA. Furthermore, it is possible that VPA leads to decreased ethanol-induced vascular damage

Effect of hydroalcoholic extract of Anethum graveolens leaves on the dentate gyrus of the hippocampus in the epileptic mice: a histopathological and immunohistochemical study

Anethum graveolens or Dill (local name: Shevid) belongs to the family of Apiaceae (Umbelliferae) and is used traditionally for the treatment of convulsion and diabetes in Iran. This study aimed to investigate the effect of hydroalcoholic extract of A. graveolens leaves on the histology of the dentate gyrus of the hippocampus in the epileptic mice kindled by Pentylenetetrazole (PTZ). In this experimental study, the epileptic BALB/c mice kindled by PTZ were randomly divided into four groups of 10 animals each. Three experimental groups received 250, 500 and 750 mg/kg/day of A. graveolens extract for 21 days. The control group received phosphate-buffered saline (PBS). After the treatment period, the mice were anesthetized, and their hippocampi were dissected for the histopathological analysis, and immunohistochemical analysis for caspase-3 activity. Histopathological examinations showed that the mean numbers of the healthy neuronal cells in the dentate gyrus of the mice received 500 mg/kg/day of A. graveolens extracts were significantly higher than those of the mice received 250 and 750 mg/kg/day of the extracts as well as the control group (P < 0.05 and P < 0.001, respectively). In addition, the results of immunohistochemical analysis revealed that in mice treated with 500 mg/kg/day of A. graveolens; the numbers of caspase-3-positive cells in the dentate gyrus were significantly lower than those of the two other test and the control groups. The findings of this study suggest that 500 mg/kg/day of the A. graveolens extract could have protective effect on the dentate gyrus of the hippocampus in the epileptic mice

Increase in CD4+Foxp3+ Regulatory T cells and Amelioration of Experimental Autoimmune Encephalomyelitis in Mice Treated with IL-27

Background and purpose: In multiple sclerosis (MS) and its murine model, experimental autoimmune encephalomyelitis (EAE), chronic inflammation damages the myelin of central nervous system. Recently, interleukin-27 (IL-27) has been recognized as a feasible choice for treatment of autoimmune diseases such as MS due to its anti-inflammatory properties. However, the underlying mechanisms have not yet been specified clearly. The present study, investigated the immunomdulatory effects of IL-27 in C57BL/6 mice with EAE. Materials and methods: In this experimental study, two groups of EAE mice (test and control groups) received intraperitoneal injection of P240-mIL-27 (200 µg) and P240 plasmid (200 µg), respectively. The disease severity was evaluated daily for 30 days. At the end of the treatment period, the mice were sacrificed and the levels of IL-17, IFN-γ, IL-6, and IL-10 were measured in splenocytes culture media using ELISA method. Also, the percentage of CD4+Foxp3+ regulatory T cells (Treg) in spleen cells was analyzed using flow cytometry. Results: Severity of EAE significantly decreased in test group (P240-mIL27), compared to that of the control group. In test group, the levels of IL-17, IFN-γ, and IL-6 were significantly lower (P<0.001), while IL-10 levels were significantly higher compared to those of the control group (P<0.001). Moreover, the percentage of Treg cells in test group was significantly higher than that of the control mice (P<0.001). Conclusion: IL-27 can be a suitable choice in treatment of inflammatory diseases such as MS via increasing Treg cells and IL-10, and suppression of inflammatory cytokines

A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East

Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population