Search

Aim: This study aimed to evaluate the distribution of PIK3CA E545K mutation in Iranian CRC patients and explored its roles in disease prognosis. Background: Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the progression of tumors. The p110a (PIK3CA), a catalytic subunit of PIK3, is mutated in many types of cancers. Exon 9 (E545K) is the most frequently mutated hotspot in PIK3CA in colorectal cancer (CRC). However, the prognostic role of PIK3CA E545K mutation needs to be elucidated. Methods: Tumors from 187 CRC patients were retrospectively collected from the Taleghani and Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, between 2010 and 2017. PIK3CA E545K status was detected in Formalin-fixed paraffin-embedded (FFPE) tissues using PCR-RFLP methods, and validated by pyrosequencing. Correlations between PIK3CA E545K mutation clinicopathological features were analyzed. Results: The frequency of PIK3CA E545K gene mutations in CRC patients was 10.7%. Significant correlations were observed in PIK3CA E545K mutation with tumor differentiation and TNM stage (p < 0.042 and p = 0.033, respectively). Kaplan-Meier analysis showed a worse prognosis in overall survival (OS) in patients with PIK3CA E545K mutation (p < 0.001). Multivariate analysis indicated that PIK3CA E545K mutation was a detrimental factor for OS (HR = 6.497, 95% CI: 2.859-14.768, p < 0.021). Conclusion: A high frequency of PIK3CA E545K mutation was detected in Iranian CRC patients. The results of the present study suggested that PIK3CA E545K mutation may be associated with poor prognosis. These findings require further confirmation via prospective studies with larger samples. [ABSTRACT FROM AUTHOR]

Aim: We aimed to explore the frequency of BRAFV600E mutation in Iranian patients with colorectal cancer (CRC) as well as its association with clinic pathological characteristic of patients. Background: CRC is the third leading cause of cancer related death. There is a growing body of data showing the association of BRAFV600E mutation with malignant transformation and clinical outcome of different tumors, including CRC. These findings suggest that BRAFV600E mutation can be used as diagnostic and/or prognostic biomarker for management of cancer patients. Patients and methods: A total of 85 patients with sporadic tumor were recruited. BRAFV600E mutation was investigated using sequencing of extracted DNAs from formalin-fixed paraffin-embedded (FFPE) tumor tissues. Electropherograms were analyzed using Laser-gene 6 software. Results: More than 95% of patients were in stage I and II and none of them were in stage IV. Patients were mostly below 55 years old and tumors were dominantly located in the distal colon. Of note, no BRAFV600E mutations were detected in our population. Conclusion: Our results showed no V600E mutation in the BRAF gene in stage I and II of CRC patients. Further studies in multi-center settings are warranted to examine the prognostic and/or predictive value of this marker in different stages of colorectal cancer patients. [ABSTRACT FROM AUTHOR]

• In this study determined the bioclimatic component loading patterns over Iran. • The results showed that the first Varimax-rotated loading pattern accounts for 51.82% of the total variances. • This study presented novel insights into the identification of bioclimatic regions in Iran. • Cluster analysis demonstrated that Iran can be divided into five bioclimatic regions based on PCA. • Spatial distribution of bioclimatic zones showing geographical dependency. The main objective of this paper is to classify bioclimatic regions in Iran for optimal environmental planning. Mean daily meteorological data of 155 well-distributed synoptic stations during 1995–2017 were extracted from Iran's Meteorological Organization. Percentage of occurrence of each thermal sensation classes was determined over all studied stations using five bioclimatic indices including Perceived Temperature (PT), Physiological Equivalent Temperature (PET), Predicted Mean Vote (PMV), Standard Effective Temperature (SET) and Universal Thermal Climate Index (UTCI). An R-mode Principal Component Analysis (PCA) was applied to a N × M (155 × 40) matrix of N = 155 stations and M = 40 total thermal thresholds based on all used indices during the considered time period. According to the results of PCA, the five loading PCs that approximately account for 98.5% of the total variance were selected for further analysis. In addition, Ward method was used for Cluster Analysis (CA) to divide the stations into different bioclimatic groups. The results illustrated that the first Varimax-rotated loading pattern which accounts for 51.82% of total variance characterized Northwest of Iran with more than 0.8 PC scores. Furthermore, cluster analysis demonstrated that Iran can be divided into five bioclimatic regions based on the R-mode PCA. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to evaluate the influence of intronic polymorphism of the SMAD7 (Mothers Against Decantaplegic Homolog 7) gene (rs2337104) on the risk of colorectal cancer (CRC) and clinicopathological features in an Iranian population. Background: SMAD7 has been identified as an antagonist of transforming growth factor beta (TGF-b)-mediating fibrosis, carcinogenesis, and inflammation. Regarding to the recent genome-wide scan, a risk locus for colorectal cancer at 18q21 has been found, which maps to the SMAD7 gene. Patients and methods: This case-control study was performed on 109 CRC patients and 109 healthy controls recruited in Taleghani Hospital. The genotyping of all samples were done by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The association of this polymorphism with the risk of CRC and clinicopathological features was investigated. Results: Our results indicated that there were no significant association between genotypic and allelic frequencies of SMAD7 polymorphism (rs2337104) and CRC risk in our population. Although the T allele is the most frequent one in this population and its frequency was 86.7% in patients compared with 91.7% in controls (OR=1.705, 95% CI= 0.916-3.172). Also, the SMAD7 genotypes were not associated with any clinicopathological characteristics in CRC patients (P>0.05). Conclusion: For the first time, this study results revealed that this SMAD7 polymorphism couldn't be a potential risk factor for CRC or a prognostic biomarker for prediction of clinicopathological features in an Iranian population. A largescale case-control study is needed to validate our results. [ABSTRACT FROM AUTHOR]

Abstract: Over the past decade, several new approaches have emerged to renewable energy education that seek to address the needs of the 21st century for sustainable energy supply systems. In addition, unlike conventional architectural education which does not cover renewable energy issues in its curriculum, these days, renewable energy education has an identity of its own within the discipline of architecture. This paper will clarify academic obstacles that are impeding the development of sustainable architectural education. These obstacles include: ambiguous definitions of sustainable architecture, confusion over the meaning of sustainability, and lack of experts in this field. In the last part of this paper we compare academic architectural education in the field of renewable energy in two countries, Iran as a developing country in Asia and Australia as a developed country in Oceania. Lessons can be drawn from these case studies in regard to the obstacles and progress in the development of sustainable architecture education. [Copyright &y& Elsevier]

Courtyards have been traditionally used as a passive design strategy in desert climates. However, few studies have quantified the thermal performance of this building archetype. This paper explored the indoor and outdoor thermal conditions of a typical courtyard house in Iran. The study was performed in two phases. The first phase showed the effect of the position of the zones located in four sides of the courtyard on their indoor energy use and indoor thermal comfort. The results showed that the east and west sides of the courtyard require the highest cooling demand due to the solar radiation in summer time. Furthermore, maximum discomfort hours occurred in the east zone. In the second phase, hourly air temperature inside and outside of the courtyard were compared during the longest day of the year (21st of June). The results showed that inside of the courtyard was 1.2 °C cooler than the outside on average. Moreover, it was observed that the temperature fluctuations outside of the courtyard were higher than the inside. To sum up, the results showed that courtyards can provide a cooler microclimate in summer time. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand the effect of urban street greenery type and arrangements on thermal comfort and heat stress in summer. Field measurements and computer simulations were carried out on East-West (E-W) and North-South (N-S) oriented streets in Isfahan, Iran. Through the field measurements in July 2014, 17 different streets were studied, followed by 15 perturbation scenarios (urban design alternatives) simulated by ENVI-met. The study showed that there is a significant and positive relationship between the Sky View Factor (SVF) and the Physiological Equivalent Temperature (PET) values. Comparison of the meteorological parameters within different street orientations showed that the effect of the SVF on the E-W streets was more significant than in N-S streets. Furthermore, greenery arrangement and building heights showed different impacts on the outdoor thermal comfort streets with different orientations. • The effect of different street greenery arrangements on thermal comfort was studied. • A significant positive relationship between SVF and PET was observed. • SVF of more than 0.6 leads to higher heat stress. • The effect of the SVF on the microclimate of E-W streets was more N-S. [ABSTRACT FROM AUTHOR]

Familial adenomatous polyposis (FAP) is an autosomal dominant colorectal cancer syndrome that is characterized by the development of multiple adenomas in the colon and rectum with high penetrance rates. This disease has specific features like the occurrence of pathogenic variations in the APC gene and diverse FAP phenotypes due to the occurrence region. In this study we aimed to evaluate pathogenic variants in exons of the APC gene in Iranian patients with FAP. A total of 35 FAP individuals were referred to the gastroenterology ward of Taleghani Hospital. As the aim of the study was to study the germline variations in the participants, the peripheral blood was collected and after the DNA extraction, PCR, and Sanger sequencing processes for the APC gene, the results were evaluated by the ACMG classification guidelines to report their pathogenicity. Accordingly, out of eight specific detected variants, three of them were novel, and the rest were reported previously. These eight variants were all truncating protein and pathogenic, and they were limited to 849-1378 codons. Overall, detected variants revealed discrepancies and parallels with previous reported cases in terms of quantity, occurrence region, and association with demographic and clinicopathological characteristics of patients. The spectrum of detected variants and the patient's phenotype showed distinct characteristics, such as occurrence in specific regions and the absence of extracolonic symptoms like Congenital hypertrophy of the retinal pigment epithelium (CHRPE). These findings open the path to comprehending the typical symptoms, their rarity, and their occurrence in the Iranian population and also due to the facts, we found that the studying of the APC gene alone for diagnosing FAP disease is not sufficient, and considering other genes are completely rational in the case of sequencing and studying the variants.

Background: Approximately 5% of colorectal cancers (CRCs) are hereditary. Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common form of recognized hereditary CRC. Although Iran, as a developing country, has a high incidence of CRC, the spectrum of variants has yet to be thoroughly investigated., Aims: This study aimed to investigate pathogenic and non-pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS)., Methods and Results: In the present study, 25 peripheral blood samples were collected from patients with sLS and high microsatellite instability (MSI-H). After DNA extraction, all samples underwent polymerase chain reaction and Sanger sequencing to identify the variants in the exons of MLH1 and MSH2 genes. The identified variants were interpreted using prediction tools, and were finally reported under ACMG guidelines. In our study population, 13 variants were found in the MLH1 gene and 8 in the MSH2 gene. Interestingly, 7 of the 13 MLH1 variants and 3 of the 8 MSH2 variants were novel, whereas the remaining variants were previously reported or available in databases. In addition, some patients with sLS did not have variants in the exons of the MLH1 and MSH2 genes. The variants detected in the MLH1 and MSH2 genes had specific characteristics regarding the number, area of occurrence, and their relationship with demographic and clinicopathologic features., Conclusion: Overall, our results suggest that analysis of MLH1 and MSH2 genes alone is insufficient in the Iranian population, and more comprehensive tests are recommended for detecting LS., (© 2023 Shahid Beheshti University of Medical Sciences. Cancer Reports published by Wiley Periodicals LLC.)

Background: Long non-coding RNAs (LncRNAs) are known to have regulatory consequences for aberrant gene expression in cancers. The aim of this study was to evaluate the expression levels of long non-encoding RNAs, BACE1 (β-secretase1) and LINC-PINT (Long Intergenic Non-Protein Coding RNA, P53 Induced Transcript), in colorectal cancer (CRC) with clinicopathological parameters., Methods and Results: Bioinformatics analysis defining effectual signalling pathways Wnt. A total of 130 tissue samples (50 fresh CRC tissues with parallel adjacent normal tissues (ADJ) accompanied with 30 normal healthy control tissue samples) were collected from the Iranian population. mRNA expression analysis was performed via Real Time Q-PCR. Statistical analysis for comparing CRC expression levels with ADJ and normal healthy tissues were carried out using Kruskal-Wallis tests. The Receiver Operating Characteristic (ROC) curve was plotted for each LNC, separately. We discovered that PINT and BACE1 expression levels were decreased and increased respectively in CRC tumour samples compared with ADJ normal and healthy tissues. Clinicopathological parameter assessment revealed a significant relationship between PINT expression, tumour location, staging and distant metastasis (p < 0.009, p < 0.014, p < 0.008, respectively). Also, BACE1 over expression was significantly associated with tumour site (p < 0.009), metastasis (p < 0.017) and histological differentiation (p < 0.028) and staging (p < 0.017). Furthermore, ROC curve plotting showed LINC-PINT LNC-BACE1 may distinguish between early and late-stage of CRC, highlighting the value of both BACE1 and PINT as CRC progression biomarkers., Conclusion: We investigated two LNCRNAs (PINT and BACE1) as potential CRC prognostic biomarkers, which are imperative for early and effective medical intervention in CRC. Expression levels of PINT and BACE1 in CRC tissue samples may serve to identify metastasis earlier, increasing patient survival rates and expediating clinical treatment options., (© 2022. The Author(s).)

Purpose: To evaluate the prognostic role of BRAF and KRAS mutations after adjustment for microsatellite instability (MSI) in Iranian colorectal cancer (CRC) patients., Methods: BRAF and KRAS mutations and MSI status were assessed in 258 Iranian subjects with CRC. Two hundred fifty-eight consecutive stages I-IV CRC patients, who underwent surgical resection of adenocarcinoma from 2012 to 2016, were enrolled in the research. Pyrosequencing and Cast-PCR methods were used to the detection of KRAS and BRAF mutations. Kaplan-Meier and Cox regression were employed to estimate hazard ratios (HR) for the association between BRAF and KRAS mutation and overall survival (OS)., Results: KRAS and BRAF mutations were detected in 36 (14%) and 15 (5.8%) cases of 258 patients with CRC, respectively. BRAF mutations that all comprised V600E and KRAS mutations was found in codon 12 and 13 (80.6% and 19.4%), respectively. KRAS mutations were detected in 19 (15.4%) patients of 123 microsatellite stable (MSS) CRC and it is significantly associated with tumor location and metastasis. BRAF and KRAS mutant vs. wild type of BRAF and KRAS, 5-year OS was 73.3% vs. 82.3% and 83.3% vs. 81.5% (long-rank P > 0.05), respectively. KRAS mutant vs. KRAS-wild-type tumors in MSS/MSI-L status CRC patients, 5-year OS was 78.9% vs. 90.4% (long-rank p = 0.046)., Conclusion: The present study revealed that BRAF and KRAS mutations were not related to the worse overall survival, while KRAS mutation can be a prognostic factor for overall survival in sporadic microsatellite-stable (MSS) status in Iranian CRC patients.

Background and Aim: One candidate gene for colorectal cancer (CRC) susceptibility is exonuclease 1 (EXO1). It is a member of RAD2 nuclease family, which plays a major role in mismatch repair, DNA replication, and recombination. Single-nucleotide polymorphisms are shown to be related with cancer incidence. The aim of the present study was to examine the association between the L757P polymorphism at exon 13 of the EXO1 gene and the risk of CRC in Iranian patients., Methods: In this case-control study, 90 cases and 98 healthy control samples were analyzed genetically. The EXO1 polymorphism, P757L, was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The obtained polymorphisms were examined for the relationship with CRC risk and also clinicopathological characteristics., Results: Our findings showed that patients with the Leu/Leu genotype have a reduced risk of CRC (adjusted odds ratio [OR] = 0.192, 95% confidence interval [CI]: 0.040-0.921) when the Pro/Leu and Pro/Pro genotypes were blended and they were considered as the reference. The Leu/Leu genotype also showed a reduced risk (adjusted OR = 0.168, 95% CI: 0.034-0.816) when the Pro/Pro genotype was a reference; nevertheless, the Pro/Leu genotype did not reveal a significant association with CRC at the same status (adjusted OR = 0.686, 95% CI: 0.367-1.284)., Conclusions: Our results provide evidence diagnosing that the Leu/Leu genotype of EXO1 showed an inverse association with CRC. In addition, despite other investigations, we could define a significant association between the Leu allele and CRC (p = 0.001).