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1.
Biochem Biophys Rep ; 38: 101731, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38766384

RESUMO

Long non-coding RNAs (lncRNAs) regulate multiple pathways and cellular mechanisms. Recent research has emphasized their involvement in the pathogenesis of complex diseases, such as Inflammatory Bowel Disease (IBD) which is characterized by chronic inflammation of the intestines. The two most common types of IBD are ulcerative colitis and Crohn's disease. CRNDE lncRNA was initially detected in colorectal cancer (CRC) and found to be involved in the tumorigenesis pathways. Further studies revealed the role of CRNDE in activating inflammation and promoting the release of inflammatory cytokines. This study utilizes the RNA-seq data analysis and bioinformatics tools to clarify the role of CRNDE in the IBD pathogenesis and confirms its expression in inflamed HT-29 and Caco-2 cell lines and also colonic and blood samples of UC patients and controls ex vivo. Based on our results, CRNDE was significantly upregulated in IBD samples compared to controls in RNA-seq data analysis and Real-time PCR of inflamed HT-29 cell line and colonic biopsies from UC patients. Additionally, predicted that its expression is positively correlated with the pro-inflammatory cytokines production. CRNDE interactions was investigated with several inflammation-related miRNAs and regulatory proteins computationally. Thus, CRNDE upregulation in the colon of IBD patients could be involved in IBD pathogenesis by promoting inflammatory pathways and targeting anti-inflammatory miRNAs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38303523

RESUMO

BACKGROUND: One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named "HT29-shE". In the present study, these cells were used to investigate the effect of pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents. METHOD: The viability and IC50 rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring. RESULTS: The findings showed that Pio and Cet at concentrations of 250 µM and 40 µg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal-- to-epithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment. CONCLUSION: Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment.

3.
Sci Rep ; 13(1): 21743, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065969

RESUMO

Gastric cancer is a complex heterogeneous disease with different molecular subtypes that have clinical implications. It is characterized by high mortality rates and limited effective therapies. Microsatellite instability (MSI) has been recognized as a subgroup with a good prognosis based on TCGA and ACRG categorizations. Besides its prognostic and predictive value, gastric cancers with high MSI exhibit different clinical behaviors. The prevalence of high MSI has been assessed in gastric cancer worldwide, especially in East Asia, but there is a lack of such information in the Middle East. Therefore, this study aimed to investigate the incidence and status of MSI in Iranian gastric cancer patients using 53 samples collected from 2015 to 2020 at Taleghani Hospital Medical Center. DNA from tumoral and normal tissues were extracted and assessed through multiplex-PCR based on five mononucleotide repeats panel. Clinicopathological variables, including age, sex, Lauren classification, lymph node involvement, TNM stage, differentiation, localization, and tumor size, were also analyzed. With 2 males and 2 females, high microsatellite instability represented a small subgroup of almost 7.5% of the samples with a median age of 60.5 years. High microsatellite instability phenotypes were significantly associated with patients aged 68 years and older (p­value of 0.0015) and lower lymph node involvement (p­value of 0.0004). Microsatellite instability was also more frequent in females, with distal gastric location, bigger tumor size, and in the intestinal type of gastric cancer rather than the diffuse type.


Assuntos
Instabilidade de Microssatélites , Neoplasias Gástricas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Incidência , Irã (Geográfico) , Prognóstico , Repetições de Microssatélites/genética
4.
Arab J Gastroenterol ; 22(3): 220-223, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34538760

RESUMO

BACKGROUND AND STUDY AIMS: Unawareness about atypical forms of celiac disease (CD) leads to the underdiagnoses of CD. This study has investigated the prevalence of CD in patients with atypical presentations, such as idiopathic low bone mineral density (ILBMD) and dyspepsia, in the Iranian population. PATIENTS AND METHODS: Two separate groups of patients who have been diagnosed with dyspepsia and ILBMD (including either osteopenia or osteoporosis of unknown cause) were screened for CD during 2016-2019. Patients were serologically screened by means of IgA anti-tissue transglutaminase (IgA anti-tTG); in case of positive results, the patients underwent endoscopic intestinal biopsy to confirm the diagnosis of CD. RESULTS: Of 200 patients with ILBMD, six (3%) had a positive result for IgA anti-tTG; in five cases (2.5%), duodenal histology confirmed the CD diagnosis. Of 290 patients with dyspepsia, 25 (8.6%) had a positive result for anti-tTG IgA; nine cases (3.7%) were histologically compatible with CD. No significant differences were found between the two groups of patients. CONCLUSIONS: The prevalence of CD in patients with atypical presentations, such as ILBMD and dyspepsia, is consistent (pvalue = 0.788) and higher than that in the general population (p value = 0.001); therefore, screening program for CD in these patients is highly recommended.


Assuntos
Doença Celíaca , Autoanticorpos , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Humanos , Imunoglobulina A , Irã (Geográfico)/epidemiologia , Prevalência
5.
Pancreatology ; 20(6): 1195-1204, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32800647

RESUMO

Late diagnosis of pancreatic cancer (PC) due to the limited effectiveness of modern testing approaches, causes many patients to miss the chance of surgery and consequently leads to a high mortality rate. Pivotal improvements in circulating microRNA expression levels in PC patients make it possible to diagnose and treat patients at earlier stages. A list of circulating miRNAs was identified in this study using bioinformatics methods in association with pancreatic cancer through analyzing four GEO microarray datasets. The value of top miRNAs was then assessed via using a machine learning method. Taking the advantage of a combinatorial approach consisting of Particle Swarm Optimization (PSO) + Artificial Neural Network (ANN) and Neighborhood Component Analysis (NCA) iterations on a collection of top differentially expressed circulating miRNAs in PC patients, facilitated ranking them by significance. MiRNA's functional analysis in the final index was performed by predicting target genes and constructing PPI networks. Remarkably, the final model consist of miR-663a, miR-1469, miR-92a-2-5p, miR-125b-1-3p and miR-532-5p showed great diagnostic results on investigated cases and the validation set (Accuracy: 0.93, Sensitivity: 0.93, and Specificity: 0.92). Kaplan-Meier survival assessments of the top-ranked miRNAs revealed that three miRNAs, hsa-miR-1469, hsa-miR-663a and hsa-miR-532-5p, had meaningful associations with the prognosis of patients with pancreatic cancer. This miRNA index may serve as a non-invasive and potential PC diagnostic model, although experimental testing is needed.


Assuntos
MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Aprendizado de Máquina , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Algoritmos , Biologia Computacional , Detecção Precoce de Câncer , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , MicroRNAs , Análise em Microsséries , Redes Neurais de Computação , Valor Preditivo dos Testes , Análise de Componente Principal , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sobrevida
6.
Sci Rep ; 10(1): 7559, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371926

RESUMO

Pancreatic cancer (PC) is a malignancy with little/no warning signs before the disease reaches its ultimate stages. Currently early detection of PC is very difficult because most patients have non-specific symptoms leading to postponing the correct diagnosis. In this study, using multiple bioinformatics tools, we integrated various serum expression profiles of miRNAs to find the most significant miRNA signatures helpful in diagnosis of PC and constructed novel miRNA diagnosis models for PC. Altogether, 27 differentially expressed miRNAs (DEMs) showed area under curve (AUC) score >80%. The most promising miRNAs, miR-1469 and miR-4530, were individually able to distinguish two groups with the highest specificity and sensitivity. By using multivariate cox regression analyses, 5 diagnostic models consisting of different combinations of miRNAs, based on their significant expression algorithms and functional properties were introduced. The correlation model consisting of miR-125a-3p, miR-5100 and miR-642b-3p was the most promising model in the diagnosis of PC patients from healthy controls with an AUC of 0.95, Sensitivity 0.98 and Specificity 0.97. Validation analysis was conducted for considered miRNAs on a final cohort consist of the microarray data from two other datasets (GSE112264 & GSE124158) . These results provide some potential biomarkers for PC diagnosis after testing in large case-control and cohort studies.


Assuntos
Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/diagnóstico , Área Sob a Curva , Biomarcadores/metabolismo , Estudos de Casos e Controles , Análise por Conglomerados , Perfilação da Expressão Gênica , Humanos , Análise Multivariada , Mapeamento de Interação de Proteínas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
Microorganisms ; 7(11)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766208

RESUMO

Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.

8.
Artigo em Inglês | MEDLINE | ID: mdl-28331559

RESUMO

Colorectal cancer (CRC) is mostly due to a series of genetic alterations that are being greatly under the influence of the environmental factors. These changes, mutational or epigenetic modifications at transcriptional forefront and/or post-transcriptional effects via miRNAs, include inactivation and the conversion of proto-oncogene to oncogenes, and/or inactivation of tumor suppressor genes (TSG). Here, a thorough review was carried out on the role of TSGs with the focus on the APC as the master regulator, mutated genes and mal-/dysfunctional pathways that lead to one type of hereditary form of the CRC; namely familial adenomatous polyposis (FAP). This review provides a venue towards defining candidate genes that can be used as new PCR-based markers for early diagnosis of FAP. In addition to diagnosis, defining the modes of genetic alterations will open door towards genome editing to either suppress the disease or reduce its progression during the course of action.

9.
Arch Iran Med ; 19(1): 2-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26702742

RESUMO

BACKGROUND: The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. METHODS: We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. RESULTS: We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). CONCLUSIONS: The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Bases de Dados Factuais , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Sistema de Registros , Fatores de Risco , Fatores Socioeconômicos
10.
World J Gastroenterol ; 20(20): 6302-8, 2014 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-24876751

RESUMO

AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in Iranian celiac disease (CD) patients and compare them to healthy Iranian controls. METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six previously reported HLA-tagging single nucleotide polymorphism to determine HLA genotypes in 59 Iranian patients with 'biopsy-confirmed' CD and in 151 healthy Iranian individuals. To test the transferability of the method, 50 cases and controls were also typed using a commercial kit that identifies individual carriers of DQ2, DQ7 and DQ8 alleles. RESULTS: In this pilot study 97% of CD cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2 (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both DQ2 and DQ8 (3%). CONCLUSION: The prevalence of DQ8 in our CD population was higher than that reported in other populations (25.4%). As reported in other populations, our results underline the primary importance of HLA-DQ alleles in the Iranian population's susceptibility to CD.


Assuntos
Doença Celíaca/genética , Frequência do Gene , Antígenos HLA-DQ/genética , Haplótipos , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Adulto Jovem
11.
Iran J Public Health ; 43(5): 630-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-26060764

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology, in which genetic factors, seem to play an important role in the disease predisposition and course. Assessment of tumor necrosis factor (TNF-α) gene polymorphisms in many populations showed a possible association with IBD. Considering the genetic variety in different ethnic groups, the aim of the present study was to investigate the association of five important single nucleo-tide polymorphisms (SNPs) in the promoter region of (TNF-α) gene with IBD in Iran. METHODS: In this case-control study, 156 Ulcerative colitis (UC) patients, 50 Crohn's disease (CD) patients and 200 sex and age matched healthy controls of Iranian origin were enrolled. The study was performed during a two year period (2008-2010) at Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. DNA samples were evaluated for (TNF-α) gene polymorphisms (including -1031, -863, -857, -308 and -238) by PCR and RFLP methods. RESULTS: The frequency of the mutant allele of -1031 polymorphism was significantly higher in Iranian patients with Crohn's disease compared to healthy controls (P=0.01, OR=1.92; 95% CI: 1.14-3.23). None of the other evaluated polymorphisms demonstrated a significant higher frequency of mutant alleles in Iranian IBD patients compared to controls. CONCLUSION: Among the five assessed (SNPs), only -1031 polymorphism of (TNF-α) gene may play a role in disease susceptibility for Crohn's disease in Iran. This pattern of distribution of (TNF-α) gene polymorphisms could be specific in this population.

12.
Turk J Gastroenterol ; 24(2): 93-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23934454

RESUMO

BACKGROUND/AIMS: Gastrointestinal disorders are important side effects of aspirin therapy, even if the low-dose enteric-coated form is administered. The aim of the current study was to present the upper and lower endoscopic features of patients with gastrointestinal hemorrhage using low-dose enteric-coated aspirin. MATERIALS AND METHODS: This prospective study was conducted among 633 consecutive patients with gastrointestinal hemorrhage who admitted to our tertiary referral hospital for endoscopy assessment. Patients were divided into two groups as low-dose aspirin users (n=168) and non-aspirin users (n=495). Aspirin users included those who were taking 80-100 mg of enteric-coated aspirin per day. RESULTS: Ulcer lesions were found in 78 patients in the aspirin user group and in 113 patients in the control group. Prevalence of duodenal ulcer was statistically similar between the two groups; however, gastric ulcer was seen more in the aspirin-user group. The use of low-dose aspirin could strongly predict gastric ulcers in the patients examined by endoscopy (p<0.001). Overall prevalence of peptic ulcer disease in those with confirmed Helicobacter pylori infection was significantly higher than in non-infected ones (p<0.001). The presence of this infection was strongly associated with peptic ulcer disease in the aspirin-user group (p<0.001). Multivariable analysis also demonstrated that the use of aspirin had a main triggering effect on short-term mortality following gastrointestinal endoscopy (p=0.003). CONCLUSIONS: Low-dose enteric-coated aspirin causes significant gastric endoscopic lesions and even predicts mortality due to progression of gastrointestinal disorders.


Assuntos
Aspirina/administração & dosagem , Úlcera Duodenal/epidemiologia , Hemorragia Gastrointestinal/epidemiologia , Inibidores da Agregação Plaquetária/administração & dosagem , Úlcera Gástrica/epidemiologia , Estudos de Casos e Controles , Endoscopia Gastrointestinal , Feminino , Infecções por Helicobacter/epidemiologia , Hematemese/epidemiologia , Humanos , Masculino , Melena/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos
13.
Cancer Biomark ; 13(6): 427-32, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24595079

RESUMO

BACKGROUND: Single nucleotide polymorphisms in mismatch repair genes may be associated with different protein expression, production, and efficiency according to allele status and influence the risk of developing colorectal cancer. OBJECTIVE: This research aimed at analyzing two important polymorphisms in MLH1 gene and their association in colorectal cancer susceptibility. METHODS: In total, 219 CRC patients and 248 healthy controls were genotyped with PCR/RFLP for I219V and IVS12-169 C>T polymorphisms in MLH1 gene. Sequencing performed to ensure work flow and results. We used unconditional logistic regression after adjusting for age and sex to evaluate the association between each polymorphism and colorectal cancer. RESULTS: The MLH1 I219V polymorphism was associated with colorectal cancer susceptibility (P=0.01). Stratified data analysis for gender demonstrated association of AG (P=0.009) and GG (P=0.021) genotypes with risk of colorectal cancer in women. In contrast there is no association with IVS 12-169 C>T polymorphism and colorectal cancer risk. CONCLUSIONS: I219V SNP might be a susceptibility factor for CRC and gender is a factor that must be considered when it is analyzing. Further tests need to be done to define it as a dependable prognosis factor.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/genética , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleotídeo Único , Curva ROC , Fatores de Risco
14.
Arab J Gastroenterol ; 12(3): 150-3, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22055594

RESUMO

BACKGROUND AND STUDY AIMS: Uraemic patients show susceptibility to gastrointestinal mucosal lesions and colonisation by Helicobacter pylori (HP). Antibiotic resistance constitutes a problem in treatment and bismuth preparations are toxic in uraemic patients. This study aimed to assess the correlation between creatinine clearance (CrCl) and eradication of HP infection with new sequential and standard triple therapeutic regimens. PATIENTS AND METHODS: A total of 120 HP-positive patients with renal function impairment and 60 control patients with HP infection were enrolled in this study. Patients were divided into four groups on the basis of CrCl and were randomly assigned to one of the two different regimens: A 14-day standard triple therapy with 20mg omeprazole bid, 1000mg amoxicillin bid and 500mg clarithromycin bid and a new sequential regimen with 20mg omeprazole bid and 1000mg amoxicillin bid both for 14 days, 500mg ciprofloxacin bid for the first 7 days and 200mg furazolidone bid for the last 7 days. Doses of amoxicillin, clarithromycin and ciprofloxacin were reduced to 50% in the cases of CrCl <30mgdl(-1). RESULTS: One hundred and sixty two out of 180 HP-positive patients (54.3% male, 51.6±12.1 years) completed treatment in the four groups and were studied. According to renal function they were classified into group A (n=39), haemodialysis (HD) patients; group B (n=37), CrCl <30mgdl(-1) without HD; group C (n=36), CrCl between 30 and 60mgdl(-1); and group D (n=50), control subjects with CrCl >90mgdl(-1). HP was successfully eradicated in 77.7% of patients with standard triple therapy and in 81.4% of patients with the sequential therapy. There was no significant difference among the study groups in the rate of HP-infection eradication with both regimens. CONCLUSION: HP eradication rates did not differ with both sequential and standard therapeutic regimens in uraemic and non-uraemic patients. We, therefore, prefer the standard triple therapy due to its simplicity and reported.


Assuntos
Antibacterianos/uso terapêutico , Creatinina/metabolismo , Inibidores Enzimáticos/uso terapêutico , Gastrite/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/imunologia , Uremia/metabolismo , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Anticorpos Antibacterianos/análise , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Seguimentos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/complicações , Gastrite/tratamento farmacológico , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Uremia/complicações , Uremia/fisiopatologia
15.
Int J Colorectal Dis ; 25(1): 63-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19707776

RESUMO

PURPOSE: The aim of the present study was to determine the profile of mismatch repair (MMR) defects in Iranian colorectal cancer patients by using immunohistochemical staining for products of four MMR genes: MLH1, MSH2, PMS2, and MSH6. METHODS: Tissue samples of 343 patients were immunostained for MLH1, MSH2, PMS2, and MSH6. Clinical and family history and survival data were compared between normal and abnormal staining patterns. RESULTS: Fourteen percent of the patients had abnormal nuclear staining for MMR proteins. MLH1 was absent in four, MLH1/PMS2 in 15, PMS2 in five, MSH2 in 12, and MSH2/MSH6 in 12 patients. These tumors were more proximal, had a nonsignificant better survival, and were more associated with positive family history. Estimation of this study of prevalence of hereditary nonpolyposis colorectal cancer in Iran was 5.5% of the total colorectal cancers. CONCLUSIONS: Along with the recommendations of the National Institute of Cancer, we recommend immunohistochemistry staining for MLH1, MSH2, PMS2, and MSH6 for determining the eligibility of patients for mutation analysis of MMR genes.


Assuntos
Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina Trifosfatases/metabolismo , Idoso , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Irã (Geográfico) , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Análise Multivariada , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/metabolismo , Coloração e Rotulagem , Análise de Sobrevida
16.
Dig Dis Sci ; 55(1): 28-31, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19241170

RESUMO

BACKGROUND: Eosinophilic esophagitis is among the causes of refractory reflux disease. Biopsy of esophagus is the gold standard for diagnosis. In this study we determined the frequency of eosinophilic esophagitis (EE) in refractory reflux cases referred to Motility Department of Shahid Beheshti Research Center of Gastroenterology and Liver Disease, Tehran, Iran. METHODS: In this cross-sectional study, 68 cases with refractory reflux disease underwent endoscopy and had biopsies taken. Specimens were stained by hematoxylin and eosin and two independent pathologists confirmed the diagnosis of eosinophilic esophagitis. RESULTS: Mean (standard deviation, SD) age at diagnosis was 41.8 (10.94) years. All had allergy or atopy, and unknown dysphagia was noted for 66%. Endoscopic findings were as follows: esophagitis (33.3%), rings (33.3%), and whitish plaques (33.3%). Prevalence of eosinophilic esophagitis was 8.8% (N = 6; one man and five women). No statistical difference in demographic variables was found between eosinophilic esophagitis cases and others, except for history of atopy, food impaction, and endoscopic features (P value <0.005). CONCLUSION: Eosinophilic esophagitis should be considered in the differential diagnosis of any cases with refractory reflux who complain of chronic unexplained dysphagia, with history of recurrent food impaction, and atopy or abnormal endoscopic features.


Assuntos
Eosinofilia/complicações , Eosinofilia/diagnóstico , Esofagite/complicações , Refluxo Gastroesofágico/etiologia , Adulto , Esofagite/diagnóstico , Esofagoscopia , Esôfago/patologia , Feminino , Humanos , Hipersensibilidade Imediata/complicações , Masculino
17.
World J Gastroenterol ; 14(43): 6717-21, 2008 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-19034977

RESUMO

AIM: To determine the expression of DNA (MMR) proteins, including hMLH1 and hMSH2, in gastric epithelial cells in the patients with or without Helicobacter pylori (H pylori)-infected gastritis. METHODS: Fifty H pylori-positive patients and 50 H pylori-negative patients were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, two antral and two corpus biopsies were taken for histological examination (Giemsa stain) and for immunohistochemical staining of hMLH1 and hMSH2. RESULTS: The percentage of epithelial cell nuclei that demonstrated positivity for hMLH1 staining was 84.14 +/- 7.32% in H pylori-negative patients, while it was 73.34 +/- 10.10% in H pylori-positive patients (P < 0.0001). No significant difference was seen between the two groups regarding the percentage of epithelial cell nuclei that demonstrated positivity for hMSH2 staining (81.16 +/- 8.32% in H pylori-negative versus 78.24 +/- 8.71% in H pylori-positive patients; P = 0.09). CONCLUSION: This study indicates that H pylori might promote development of gastric carcinoma at least in part through its ability to affect the DNA MMR system.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Reparo de Erro de Pareamento de DNA/fisiologia , Gastrite/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Adulto , Biópsia , Epitélio/metabolismo , Epitélio/patologia , Feminino , Mucosa Gástrica/metabolismo , Gastrite/patologia , Infecções por Helicobacter/patologia , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteínas MutL , Estômago/patologia
18.
Med Princ Pract ; 17(2): 126-30, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18287796

RESUMO

OBJECTIVES: To evaluate the frequency and severity of fibrosis, and also the association of various viral and host factors of steatosis in Iranian patients with hepatitis C (CHC). SUBJECTS AND METHODS: Eighty treatment-naive CHC patients, age 37.6 +/- 11.77 years, were studied. Percutaneous liver biopsy was performed for all patients. Based on pathology reports, patients were divided into two groups: with and without significant steatosis. Hepatitis C virus RNA (HCV-RNA), various viral and host factors, and biochemical findings and genotyping of HCV were compared in the two groups. RESULTS: Of the 80 patients, 42 (52.5%) had pathologic evidence of significant steatosis. The mean serum level of cholesterol, triglyceride, glucose, and gamma-glutamyl transpeptidase as well as the mean body mass index, viral load, stage of fibrosis and frequency of genotype 3 were significantly higher in the patients with than those without steatosis (p < 0.05). In multivariate analysis, only genotype 3 and viral load had significant association with steatosis. In patients with genotype 3 infection, the mean viral load in those with and without steatosis was 1,623,357 +/- 833,543.46 and 821,262.1 +/- 924,480 copies/ml, respectively, and the difference was statistically significant (p = 0.009). The mean viral load in patients with genotype 1 infection was not significantly different between the two groups. The mean stage of fibrosis was higher in the group that had significant steatosis (p < 0.05). CONCLUSION: Steatosis is a common finding in Iranian patients with CHC. Infection with HCV genotype 3 and high viral load in these patients are associated with significant steatosis.


Assuntos
Fígado Gorduroso/epidemiologia , Fígado Gorduroso/virologia , Hepatite C Crônica/complicações , Adulto , Estudos Transversais , Fígado Gorduroso/patologia , Feminino , Genótipo , Hepatite C Crônica/genética , Hepatite C Crônica/patologia , Humanos , Irã (Geográfico)/epidemiologia , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Análise Multivariada , Prevalência , Fatores de Risco , Carga Viral
19.
Eur J Gastroenterol Hepatol ; 19(12): 1075-81, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17998832

RESUMO

BACKGROUND: Decision tree classification is a standard machine learning technique that has been used for a wide range of applications. Patients with inflammatory bowel disease (IBD) are at increased risk of developing low bone mineral density (BMD). This study aimed at developing a new approach to select truly affected IBD patients who are indicated for densitometry, hence, subjecting fewer patients for bone densitometry and reducing expenses. MATERIALS AND METHODS: Simple decision trees have been developed by means of WEKA (Waikato Environment for Knowledge Analysis) package of machine learning algorithms to predict factors influencing the bone density among IBD patients. The BMD status was the outcome variable whereas age, sex, duration of disease, smoking status, corticosteroid use, oral contraceptive use, calcium or vitamin D supplementation, menstruation, milk abstinence, BMI, and levels of calcium, phosphorous, alkaline phosphatase, and 25-OH vitamin D were all attributes. RESULTS: Testing showed the decision trees to have sensitivities of 65.7-82.8%, specificities of 95.2-96.3%, accuracies of 86.2-89.8%, and Matthews correlation coefficients of 0.68-0.79. Smoking status was the most significant node (root) for ulcerative colitis and IBD-associated trees whereas calcium status was the root of Crohn's disease patients' decision tree. CONCLUSION: BD specialists could use such decision trees to reduce substantially the number of patients referred for bone densitometry and potentially save resources.


Assuntos
Árvores de Decisões , Diagnóstico por Computador/métodos , Doenças Inflamatórias Intestinais/complicações , Osteoporose/diagnóstico , Osteoporose/etiologia , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Algoritmos , Densidade Óssea , Colite Ulcerativa/complicações , Colite Ulcerativa/fisiopatologia , Doença de Crohn/complicações , Doença de Crohn/fisiopatologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Fatores de Risco , Fumar/efeitos adversos , Fumar/fisiopatologia , Software
20.
World J Gastroenterol ; 12(35): 5658-62, 2006 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-17007018

RESUMO

AIM: To examine the relationship between H. pylori and gastro-oesophageal reflux disease (GORD) in Iran. METHODS: In this study 51 GORD patients (referred to endoscopy at Taleghani hospital) were compared with 49 age-sex matched controls. Diagnosis of H. pylori was made by gastric mucosal biopsy and rapid urease test (positive if the result of one or both diagnostic methods was positive). Updated Sydney system was used to report histopathological changes. RESULTS: The frequency of H. pylori infection based on rapid urease test and histology was 88.2% (45) in patients and 77.6% (38) in controls, which showed no significant difference. The frequency of H. pylori infection was significantly higher in the antrum than in the corpus and cardia. The mean activity, inflammation, and gastritis scores were also higher in the antrum of patients than in the antrum of controls. The mean scores were significantly higher in the corpus of controls than in the corpus of patients. Diffuse active gastritis was observed in a significantly larger number of controls, while the frequency of diffuse chronic gastritis was higher in patients. There was no significant difference in the frequency of other histological findings between patients and controls. CONCLUSION: H. pylori infection cannot prevent GORD in this region.


Assuntos
Esofagite Péptica/microbiologia , Esôfago/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cárdia/microbiologia , Cárdia/patologia , Estudos de Casos e Controles , Esofagite Péptica/epidemiologia , Esofagite Péptica/patologia , Esôfago/patologia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Antro Pilórico/microbiologia , Antro Pilórico/patologia
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