Custom-designed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test for profiling of promoter methylation in ovarian and endometrial cancers

Background: Epithelial ovarian cancer is the most common type of ovarian cancer and is the most lethal gynecologic cancer due to its late diagnosis. Compared to ovarian cancer, endometrial carcinoma, as the most common gynecologic malignancy, is referred to as the “curable cancer”, as it can be detected early. As aberrant promoter methylation patterns are a common change in human cancer, detection of promoter methylation status may help in early diagnosis. In this study, we used a custom-designed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay as a rapid and easy method, to simultaneously detect the methylation status of multiple genes in ovarian and endometrial cancer samples. Aims: To design and test an MS-MLPA assay for analyzing promoter methylation of four genes associated with ovarian and endometrial cancers. The selected genes were HNF1 homeobox B (HNF1β), Ten-eleven translocation 1(TET1), L1 cell adhesion molecule (L1CAM), and AT-rich interactive domain 1A (ARID1A). These genes are known to have expression changes by DNA methylation. Methods: The promoter DNA methylation patterns of these four genes were analyzed in 15 cancer cell lines and 5 normal cell lines and DNAs using bisulfite sequencing. Six synthetic probe pairs were designed and optimized by applying them to cancer and normal cell lines and normal DNAs and comparing the results with those of bisulfite sequencing. Finally, the MS-MLPA assay was performed on patient specimens according to the MRC-HOLLAND MS-MLPA general protocol and methylation frequencies were calculated from MS-MLPA data. Results and conclusion: The MS-MLPA assay gave accurate methylation results with the 170 samples assayed. The HNF1B, L1CAM, and TET1 Genes were observed methylated in tumor samples whereas they were not methylated in the normal samples or showed very little methylation, suggested to be favorable diagnostic markers. MS-MLPA robustly and sensitively detects the promoter DNA methylation status

A Role for the Circadian Clock in Colorectal Cancer Progression: A Comprehensive Molecular Analysis on the Interplay between Core-Clock Genes and Metastasis-related Cellular Processes

Störungen der zirkadianen Uhr beeinflussen zelluläre Prozesse wie Transkription, Zellzyklus und Stoffwechsel und können Tumorentstehung fördern. Unsere Studien untersuchten die Auswirkungen solcher Störungen auf die Krebsentwicklung durch Herunterregulation oder Ausschalten von Kern-Uhrgenen wie BMAL1 (ARNTL), PER2 oder NR1D1. Wir verwendeten in vitro- und in vivo-Modellen mit Darmkrebszelllinien HCT116, SW480 und SW620. Diese Manipulationen veränderten die zirkadiane Expression von MYC, WEE1 und TP53 (wichtig für Zellzyklus und Apoptose) sowie MACC1 (verbunden mit epithelial-mesenchymaler Transition und Metastasierung). Diese Veränderungen beeinflussen Zellproliferation, Apoptose, Migration und Invasion. Das Ausschalten von NR1D1 verringerte die Zellbeweglichkeit in vitro und reduzierte die Mikrometastasenbildung in vivo, begleitet von geänderten SNAI1 und CD44-Expressionen. MACC1 wird in HCT116-Wildtypzellen zirkadian exprimiert, was nach dem Ausschalten der Kern-Uhrgene gestört war. Wir identifizierten außerdem eine MACC1-NR1D1-Protein-Interaktion, die eine neue Regulierungsachse bei der Darmkrebsprogression darstellt. Unsere Daten zeigen, dass MACC1-Modulation den zirkadianen Phänotyp und Krebsfortschritt beeinflusst. MACC1-Knockout reduzierte die BMAL1-Oszillationsperiode, während seine Überexpression den gegenteiligen Effekt hatte. Dieses Zusammenspiel unterstreicht die Komplexität der Mechanismen bei Darmkrebs und die Rolle der zirkadianen Uhr bei der Metastasierung. Unsere Ergebnisse heben die Rolle von Kern-Uhrgenen bei Krebsprozessen wie Migration und Invasion hervor und bieten Einblicke in das MACC1-zirkadiane Uhr-Zusammenspiel in Darmkrebs. Zukünftige Forschungen könnten chronotherapeutische Strategien entwickeln, um Krebsbehandlungen zu personalisieren und zu verbessern.Disruptions of the circadian clock affect cellular processes like transcription, cell cycle, and metabolism, potentially triggering tumorigenesis. Our studies examined the effects of these disruptions on cancer by downregulating or knocking out core-clock genes BMAL1 (ARNTL), PER2, or NR1D1. For this, we used in vitro and in vivo models with colorectal cancer (CRC) cell lines HCT116, SW480, and SW620. Core-clock gene manipulations altered circadian expression of MYC, WEE1, TP53 (involved in cell cycle and apoptosis), and MACC1 (linked to epithelial-mesenchymal transition and metastasis formation), affecting proliferation, apoptosis, migration, and invasion. NR1D1 knockdown reduced cell motility in vitro and decreased micrometastasis formation in vivo, with altered SNAI1 and CD44 expression. Furthermore, we showed that MACC1 is circadian expressed in HCT116 wild-type cells, and that its rhythmic expression is disrupted after core-clock gene knockout. We also found MACC1-NR1D1 protein-protien interactions, suggesting a new regulatory axis in CRC progression. Our data show MACC1 modulation impacts the circadian clock phenotype and cancer progression. Remarkably, MACC1 knockout reduced BMAL1 promoter oscillation period, while its overexpression had the opposite effect. This interplay highlights the circadian clock complexity and its role in CRC metastasis. Our findings underscore vital roles for core-clock genes in cancer processes like migration and invasion, providing insights into MACC1-circadian clock interplay in CRC. Future research may develop chronotherapeutic strategies for more personalized and effective treatments

Extending Survival in a Patient with Extensive Stage of Small Cell Lung Cancer Presenting with Superior Vena Cava Syndrome as an Initial Symptom: A Case Study

Introduction: Superior vena cava (SVC) syndrome which is defined as the obstruction of blood flow through the SVC vein, often affecting patients with malignancy especially small cell lung cancer (SCLC) and is potentially an emergent condition needing prompt management. It is an ominous sign with poor prognosis and a mean of 8-10 months survival rate. Case presentation: Here we present a middle-aged man who presented with fascial swelling and dyspnea with final diagnosis of advanced SCLC. Combination of multiple chemotherapy regimen, prophylactic brain radiation with administration of anticoagulant drugs were performed for him leading toward extension of his survival to 28 months. Conclusion: These therapeutic approaches may lead to extending the survival in patients with SVC syndrome and SCLC

Extending Survival in a Patient with Extensive Stage of Small Cell Lung Cancer Presenting with Superior Vena Cava Syndrome as an Initial Symptom: A Case Study

Introduction: Superior vena cava (SVC) syndrome which is defined as the obstruction of blood flow through the SVC vein, often affecting patients with malignancy especially small cell lung cancer (SCLC) and is potentially an emergent condition needing prompt management. It is an ominous sign with poor prognosis and a mean of 8-10 months survival rate. Case presentation: Here we present a middle-aged man who presented with fascial swelling and dyspnea with final diagnosis of advanced SCLC. Combination of multiple chemotherapy regimen, prophylactic brain radiation with administration of anticoagulant drugs were performed for him leading toward extension of his survival to 28 months. Conclusion: These therapeutic approaches may lead to extending the survival in patients with SVC syndrome and SCLC

Hemodynamic Changes After Intubation of Endotracheal Tube, LMA Classic™, and I-gel in Patients Candidates for Elective Eye Surgery

Background: One of the concerns of the anesthetists in performing surgical procedures is hemodynamic changes after laryngoscopy and tracheal tube intubation. In these cases, stress response with the release of catecholamines leads to increased blood pressure and heart rate in patientswhoare prone to cardiovascular disease and cerebral events, leading to the life-threatening risks. Objectives: Endotracheal Intubation (ETT) is one of the most stress response techniques for airway management. Here, wecompare the effects of tree devices including ETT, laryngeal mask airway (LMA) classic, and I-gel with each other. Methods: The present study investigated the hemodynamic changes in patients undergoing elective cataract surgery after the intubation of an endotracheal tube. This clinical trial study was conducted on 75 patients with ASA class I or II in both genders and in the age group of 50 - 65 years old. The effects of LMA Classic™ and I-gel were also investigated. In this study, patients’ vital signs such as pulse rate, systolic blood pressure, and diastolic blood pressure were measured and recorded at times before insertion of the airway devices, one, two, and five minutes after the insertion. Results and Conclusions: Before the start of the operation, there was no significant difference between the groups in terms of hemodynamic parameters. Immediately before inserting ETT, LMA, or I-gel, the heart rate and systolic and diastolic blood pressure increased significantly in all groups. Our results generally showed that the hemodynamic changes due to the I-gel insertion compared to the tracheal tube and LMA Classic™ insertion followed minor adjustments. In a comparison between the insertion of the endotracheal tube and LMA Classic™, the use of the LMA Classic™ was associated with more stabilit

Autism Spectrum Disorders in Iran

How to Cite this Article: Mohammadi MR, Salmanian M, Akhondzadeh Sh. Autism Spectrum Disorders in Iran. Iranian Journal of Child Neurology2011;5(4):1-9.ObjectiveAutistic disorder, Asperger syndrome, and PDD-Not Otherwise Specified are subsets of autism spectrum disorders (ASDs), which are characterized by impairments in social communication and stereotyped behavior. This article reviews the prevalence, etiology, diagnosis, and treatment of ASDs in Iran.Materials & MethodsWe searched PubMed, ISI Web of Science, and 4 Iranian databases (IranPsych,IranMedex, Irandoc and Scientific Information Database (SID) to find Iranian studies on  ASDs. The results of 39 investigations, comprising original, review and editorial articles; proceedings; and available dissertations were categorized by prevalence, etiology, diagnosis, and treatment.ConclusionSeveral preliminary investigations have been done to evaluate the prevalence of ASDs, and risk factors and effective variables have been studied with regard to etiology. The diagnostic evaluation of ASDs, especially based on EEG, and several pharmacological and behavioral interventions for ASD have been implemented in Iran. Mental health, stress levels, and personality characteristics were examined in the parents of children with ASDs, which were focused on mothers.ReferencesFirst MB, Frances A, Pincus HA. DSM-IV-TR: Handbook of differential diagnosis. United States of America:American Psychiatric Publishing; 2002.Parker S, Zuckerman B, Augustyn M. Developmental and behavioral pediatrics, 2 th ed. United States of America:Lippincott Williams & Wilkins; 2005.Howlin P. 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Critical thinking and clinical decision making in nurse‏

BACKGROUND: Today, nurses are exposed to everchanging complicated conditions in health care services, they provide. To be able to cope with these conditions effectively, they should be competent decision makers. Besides, as decision making conditions get more complicated, using critical thinking is a need. The current study was carried out to evaluate the relationship between critical thinking and clinical decision making, in nurses of critical and general care units of hospitals in Isfahan. In addition, it is also aimed to compare the nurses of critical and general units in critical thinking and clinical decision making. METHODS: This is a correlation, descriptive study of cross-sectional type. The participants are 140 nurses; 70 working in critical care unit and 70, working in general units. Sampling method was random stratified sampling and the data was collected using a questionnaire with three sections; containing items on demographic data, clinical decision making and California critical thinking skills test. The validity and reliability of the questionnaire was approved using content validity, test-retest method and internal correlation test. The data was analyzed using variance analysis, Pearson correlation and t-test. RESULTS: The mean score of critical thinking and clinical decision making was 10.61, 63.27 and 10.67, 61.66 for nurses of critical care and general units, respectively. No statistical significant difference between two groups was observed in the area of clinical decision making and critical thinking. In addition, no statistical correlation was observed between the clinical decision making and critical thinking. CONCLUSIONS: The findings of the study demonstrated that the mean score of critical thinking was low in nurses. Probably, it originates from the educational system shortages and also, the professional environment problems. Some experts believe that the reason for lack of correlation between critical thinking and clinical decision making goes back to the absence of appropriate tool to measure the correlatio

Analysis of the Factors Affecting the Implementation of Virtual R&D in Iranian Tile and Ceramic Companies Using Structural Equation Modeling Approach

The final goal of this study is to provide a model with structural modeling approach of virtual R & D implementation in Iranian ceramic tile companies and small and medium-sized industries and services are one of the broadest fields of activity of manufacturing and economic enterprises that are of great importance. Accordingly, the establishment and expansion of research and development systems in order to infuse new sciences and technologies into this industry is of great importance