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Biomedical subjects

M Sotoudeh

Publications and source records attributed to M Sotoudeh.

12 recordsLinked to original sources

Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin.

BACKGROUND: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. PATIENTS AND METHODS: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The frequency and the spectrum of K-ras mutations were compared with those observed in a series of colorectal cancer patients from Italy. RESULTS: K-ras mutations were observed in 68/182 (37.4%) cases. Mutation frequencies were similar in HNPCC-associated, sporadic MSI-H and sporadic microsatellite-stable (MSS) tumors. However, the G13D substitution was more frequent in HNPCC (3/4, 75%) and sporadic MSI-H (7/11, 63.6%) tumors compared to sporadic MSS tumors (11/53, 20.4%) (P <0.01). Comparison of mutations in the two series from Iran and Italy showed a significantly higher frequency of G13D among Italian patients. CONCLUSIONS: While the frequency of K-ras mutations could be similar, the mutational spectrum could be differentially influenced by genetic and environmental factors.

Codon↗

Golestan cohort study of oesophageal cancer: feasibility and first results.

To investigate the incidence of oesophageal cancer (EC) in the Golestan province of North-East Iran, we invited 1349 rural and urban inhabitants of Golestan province aged 35-80 to undergo extensive lifestyle interviews and to provide biological samples. The interview was repeated on a subset of 130 participants to assess reliability of questionnaire and medical information. Temperature at which tea was consumed was measured on two occasions by 110 subjects. Samples of rice, wheat and sorghum were tested for fumonisin contamination. An active follow-up was carried out after 6 and 12 months. A total of 1057 subjects (610 women and 447 men) participated in this feasibility study (78.4% participation rate). Cigarette smoking, opium and alcohol use were reported by 163 (13.8%), 93 (8.8%) and 39 (3.7%) subjects, respectively. Tobacco smoking was correlated with urinary cotinine (kappa = 0.74). Most questionnaire data had kappa > 0.7 in repeat measurements; tea temperature measurement was reliable (kappa = 0.71). No fumonisins were detected in the samples analysed. During the follow-up six subjects were lost (0.6%), two subjects developed EC (one dead, one alive); in all, 13 subjects died (with cause of death known for 11, 84.6%). Conducting a cohort study in Golestan is feasible with reliable information obtained for suspected risk factors; participants can be followed up for EC incidence and mortality.

Adult↗

Epidemiologic features of upper gastrointestinal tract cancers in Northeastern Iran.

Previous studies have shown that oesophageal and gastric cancers are the most common causes of cancer death in the Golestan Province, Iran. In 2001, we established Atrak Clinic, a referral clinic for gastrointestinal (GI) diseases in Gonbad, the major city of eastern Golestan, which has permitted, for the first time in this region, endoscopic localisation and histologic examination of upper GI cancers. Among the initial 682 patients seen at Atrak Clinic, 370 were confirmed histologically to have cancer, including 223 (60%) oesophageal squamous cell cancers (ESCC), 22 (6%) oesophageal adenocarcinomas (EAC), 58 (16%) gastric cardia adenocarcinomas (GCA), and 58 (16%) gastric noncardia adenocarcinomas. The proportional occurrence of these four main site-cell type subdivisions of upper GI cancers in Golestan is similar to that seen in Linxian, China, another area of high ESCC incidence, and is markedly different from the current proportions in many Western countries. Questioning of patients about exposure to some known and suspected risk factors for squamous cell oesophageal cancer confirmed a negligible history of consumption of alcohol, little use of cigarettes or nass (tobacco, lime and ash), and a low intake of opium, suggesting that the high rates of ESCC seen in northeastern Iran must have other important risk factors that remain speculative or unknown. Further studies are needed to define more precisely the patterns of upper GI cancer incidence, to test other previously suspected risk factors, and to find new significant risk factors in this high-risk area.

Adenocarcinoma↗

Coeliac disease in Iranian type I diabetic patients.

BACKGROUND: The association between coeliac disease and type I diabetes mellitus has been evaluated in some previous studies, but its prevalence in Iranian diabetic patients remains unknown. AIM: To evaluate the prevalence of coeliac disease in patients with type I diabetes mellitus in Iran. PATIENTS: A total of 250 consecutive patients (102 male and 148 female) with type I diabetes mellitus. METHODS: Total serum immunoglobulin A level and immunoglobulin A endomysial antibody was measured for all patients. Endoscopy and biopsy of the duodenum were performed for immunoglobulin A endomysial antibody-positive patients and pathologic evaluation was done according to modified Marsh classification. RESULT: The mean age of the patients was 18.7 years (range: 2-55 years). Total serum immunoglobulin A was in the normal range for all patients. Immunoglobulin A endomysial antibody was positive in six (2.4%) patients (all of them were females; P = 0.04). Duodenal biopsy samples revealed grade I in two patients, grade II in three patients and grade IIIb in one patient (modified Marsh classification). Patients with coeliac disease and diabetes mellitus were older than patients with diabetes mellitus alone (mean age: 29.5 years versus 18.4 years; P < 0.001). There was a trend for longer duration of diabetes mellitus in coeliac patients than in patients without it (mean age: 17.3 years versus 12.5 years; P = 0.16). CONCLUSION: The prevalence of coeliac disease in Iranian patients with type I diabetes mellitus is relatively high (2.4%). Since almost half of the patients with coeliac disease are asymptomatic, all patients with type I diabetes mellitus should be screened for coeliac disease regardless of the presence of symptoms, at diagnosis of diabetes mellitus and with regular intervals in the follow up.

Adolescent↗

Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran.

BACKGROUND/AIMS: Ardabil Province, in northwestern Iran, has the highest rate of gastric (predominantly cardia) adenocarcinoma in Iran. This study aimed to investigate the feasibility of endoscopic screening and to look for associated Helicobacter pylori infection and gastric precancerous lesions. METHODS: One thousand one hundred and five adult volunteers, residents of Ardabil and Meshkinshahr, districts, 40 years old and above were selected and invited by a simple random household canvass in rural and urban locations. Informed consents were obtained and upper gastrointestinal video endoscopy was performed to biopsy all visible lesions and standard sites in the antrum, corpus, and cardia. RESULTS: One thousand and eleven of the invited individuals agreed to participate, including 494 men and 517 women, with a mean (SD) age of 53.32 (10.39) years. Endoscopy was well tolerated by all subjects; 96.7% of antral and 80.7% of cardia mucosal biopsies were satisfactory. The urease test or histology for H pylori was positive in at least 89.2% of subjects. Histological evidence of mucosal atrophy was seen in 39.3% of antral and 21.9% of cardia samples. Chronic gastritis with or without activity, reactive atypia of glandular epithelium, intestinal metaplasia, dysplasia, and cancer were found in 95.1%, 38.0%, 8.7%, 0.2%, and 0.3% of antral and 85.3%, 22.9%, 3.8%, 0.3%, and 0.1% of cardiac biopsies, respectively. CONCLUSION: Endoscopic screening for upper gastrointestinal diseases was feasible and well tolerated in Ardabil, Iran. Most subjects showed H pylori infection. Atrophic gastritis, reactive atypia, and intestinal metaplasia were common in antrum, corpus, and cardia subsites.

Adenocarcinoma↗

Endoscopic esophageal cancer survey in the western part of the Caspian Littoral.

After a hiatus of 30 years an attempt is now being made to re-assess the previously reported very high esophageal cancer incidence rates in the Caspian Littoral. The extraordinarily high incidence rates found in the eastern side of the Littoral, were re-confirmed five years ago for the Turkoman region, using esophageal balloon cytology supplemented by esophagoscopy of suspected cases. The focus this time was on the Ardabil province in the western side of the Caspian Littoral, where the rates reported 30 years ago were moderately high. A pilot chromoendoscopic screening program was scheduled for 650 asymptomatic adults from a randomly selected part of the city of Ardabil and adjoining villages, to evaluate the overall patterns of esophageal disease and to establish the utility of endoscopy as an esophageal cancer screening tool. 504 healthy volunteers, giving a compliance rate of 77.5%, submitted to esophagogastroscopy without any mishaps. Contrary to expectation, no dysplasia or esophageal cancer was found in 914 satisfactory biopsy specimens. Total absence of esophageal cancer or precursor dysplastic changes in the surveyed population in the western part of the Caspian Littoral was at variance with the cancer registry findings of three decades ago for the western part of the Littoral. A plausible explanation could be the improved socio-economic conditions and life style changes which have taken place in the recent past all along the Caspian Littoral, except in the Turkoman Plain.

Adult↗

Cyclosporin A is a promising alternative to corticosteroids in autoimmune hepatitis.

Autoimmune hepatitis (AIH), a chronic T-cell-mediated liver injury, is treated with corticosteroids with or without Azathioprine. Corticosteroids are not universally effective and have serious side effects. Cyclosporin A was effective in refractory cases. To assess efficacy and safety of Cyclosporin A (Neoral) in induction of remission in AIH patients this study was performed. Nineteen consenting AIH patients (nine treatment-naive) were treated with cyclosporin A in an open label trial and followed for 26 weeks. Liver biopsy was done and hepatitis activity index (HAI) determined at the beginning and end of treatment. Four patients did not complete the study for various reasons. Mean AST and ALT levels decreased from 948.7 +/- 103.5 and 454.8 +/- 354 to 100.6 +/- 111.8 and 78.5 +/- 40.3 (P < 0.03, P < 0.001) respectively. HAI decreased from 15.2 +/- 3.16 to 7.14 +/- 4.01 (P < 0.005). Serum creatinine did not change significantly. In conclusion, low-dose cyclosporin A appears to be safe and effective even in treatment-naive autoimmune hepatitis patients. Randomized controlled trials are warranted.

Adolescent↗

Various durations of a standard regimen (amoxycillin, metronidazole, colloidal bismuth sub-citrate for 2 weeks or with additional ranitidine for 1 or 2 weeks) on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A randomized controlled trial.

INTRODUCTION: One of the most economical and effective therapeutic regimens for eradication of Helicobacter pylori is the classic triple therapy with amoxycillin or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor antagonists to these drugs may heighten the rate of eradication and shorten the duration. We therefore performed a randomized controlled trial comparing twice daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult patients with duodenal ulcer and H. pylori infection were randomly assigned to one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid, bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300 mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after starting the treatment. The rapid urease test and histology from antrum and corpus, and/or 14C- urea breath test were used to determine H. pylori eradication six weeks after starting the treatment. RESULTS: In total, 195 patients were followed up for 6 weeks. The most frequent drug side-effects were unpleasant taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution in all treatment groups. Endoscopy and 14C- urea breath test were performed for 178 and 123 patients, respectively. Eradication of H. pylori was documented in 19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3, respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2 versus group 3; difference not significant for group 1 versus group 2). An intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80 (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks post-treatment, the most sensitive test for evaluation of eradication of H. pylori was histology. CONCLUSION: Although combined use of an H2-receptor antagonist and twice daily triple therapy in a two-week regimen is more effective than two-week triple or one-week quadruple therapy in Iranian patients, none of these regimens is ideal in countries with a probable high rate of resistant and strongly toxic strains of H. pylori.

Adult↗

Shear stress activates p60src-Ras-MAPK signaling pathways in vascular endothelial cells.

The aim of this study was to elucidate the upstream signaling mechanism that mediates the fluid shear stress activation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinases (ERKs), in vascular endothelial cells (ECs). Our results indicate that p60src is rapidly activated by fluid shear stress in bovine aortic endothelial cells (BAECs). Shear stress induction of the hemagglutinin (HA) epitope-tagged HA-JNK1 and the Myc epitope-tagged Myc-ERK2 was significantly attenuated by v-src(K295R) and c-src(K295R), the kinase-defective mutants ofv-src and c-src, respectively. HA-JNK1 and Myc-ERK2 were activated by c-src(F527), a constitutively activated form of p60src, and the activation was abolished by RasN17, a dominant-negative mutant of p2lras. In contrast, although HA-JNK1 and Myc-ERK2 were also activated by RasL61, an activated form of p21ras, the activation was not affected by v-src(K295R). These results indicate that p60src is upstream to the Ras-JNK and Ras-ERK pathways in response to shear stress. The shear stress inductions of the promoters of monocyte chemotactic protein-1 (MCP-1) and c-fos, driven by TPA-responsive element (TRE) and serum-responsive element (SRE), respectively, were attenuated by v-src(K295R). This attenuation is associated with decreased transcriptional activities of c-Jun and Elk-1, the transcription factors targeting TRE and SRE, respectively. Thus, p60src plays a critical role in the shear stress activation of MAPK pathways and induction of Activating Protein-1 (AP- 1)/TRE and Elk-1/SRE-mediated transcription in ECs.

Animals↗

A strain device imposing dynamic and uniform equi-biaxial strain to cultured cells.

The objective of this study is to design a new apparatus to allow the control of the magnitude and frequency of dynamic stretch applied uniformly to cells cultured on a silicon elastic membrane. The apparatus is designed to produce equi-biaxial dynamic stretches with area changes ranging from 0% to 55% and frequencies ranging from 0 to 2 Hz. Homogeneous finite strain analysis using triangles of markers was performed to compute the symmetric two-dimensional Lagrangian strain tensor on the membrane. Measurements of strain in both static and dynamic conditions showed that the shear component of the strain tensor (Erc) was near zero, and that there was no significant difference between radial (Err) and circumferential (Ecc) components, indicating the attainment of equi-biaxial strain. Bovine aortic endothelial cells were transiently transfected with a chimeric construct in which the luciferase reporter is driven by TPA-responsive elements (TRE). The transfected cells cultured on the membrane were stretched. The luciferase activity increased significantly only when the cells were stretched by 15% or more in area. Cells in different locations of the membrane showed similar induction of luciferase activities, confirming that strain is uniform and equi-biaxial across the membrane.

Animals↗