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1.  Expression, Tissue Distribution and Function of miR-21 in Esophageal Squamous Cell Carcinoma 
PLoS ONE  2013;8(9):e73009.
MiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells.
MiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion.
MiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4.
MiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in “activating” fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment.
PMCID: PMC3769386  PMID: 24039846
2.  Patterns of food and nutrient consumption in northern Iran, a high-risk area for esophageal cancer 
Nutrition and cancer  2009;61(4):475-483.
To investigate patterns of food and nutrient consumption in Golestan province, a high-incidence area for esophageal cancer (EC) in northern Iran.
Twelve 24-hour dietary recalls were administered during a one year period to 131 healthy participants in a pilot cohort study. We compare here nutrient intake in Golestan with Recommended Daily Allowances (RDAs) and Lowest Threshold Intakes (LTIs). We also compare the intake of 27 food groups and nutrients among several population subgroups, using mean values from the twelve recalls.
Rural women had a very low level of vitamin intake, which was even lower than LTIs (P < 0.01). Daily intake of vitamins A and C was lower than LTI in 67% and 73% of rural women, respectively. Among rural men, the vitamin intakes were not significantly different from LTIs. Among urban women, the vitamin intakes were significantly lower than RDAs, but were significantly higher than LTIs. Among urban men, the intakes were not significantly different from RDAs. Compared to urban dwellers, intake of most food groups and nutrients, including vitamins, was significantly lower among rural dwellers. In terms of vitamin intake, no significant difference was observed between Turkmen and non-Turkmen ethnics.
The severe deficiency in vitamin intake among women and rural dwellers and marked differences in nutrient intake between rural and urban dwellers may contribute to the observed epidemiological pattern of EC in Golestan, with high incidence rates among women and people with low socioeconomic status, and the highest incidence rate among rural women.
PMCID: PMC2796961  PMID: 19838919
esophageal cancer; Iran; Caspian Littoral; Golestan: Turkmen; diet record
3.  Epidemiology of upper gastrointestinal cancers in Iran: A sub site analysis of 761 cases 
AIM: To define the sub site distribution of upper gastrointestinal cancers in three provinces of Iran.
METHODS: The study was carried out in three provinces in Iran: Ardabil, Golestan, and Tehran. In Arbabil and Golestan, the data was collected from the sole referral center for gastrointestinal cancers and the local cancer registry. For Tehran province, data from two major private hospitals were used. All gastric and esophageal cancer patients diagnosed during the period from September 2000 and April 2002 were included in the study.
RESULTS: A total of 761 patients with upper gastrointestinal cancers were identified, 314 from Ardabil, 261 from Golestan, and 186 from Tehran. In Tehran, the relative rate of cancer increased from the upper esophagus to the distal stomach. In Golestan, the reverse pattern was observed. In Ardabil, the mid portion (distal esophagus and proximal stomach) was involved most frequently.
CONCLUSION: There were considerable variations in the sub site of upper gastrointestinal cancers in the three provinces studied. We cannot provide any explanation for this variation. Further research aimed at explaining the discrepancies in sub site distribution of upper gastrointestinal cancers may help identify important risk factors.
PMCID: PMC4171328  PMID: 17879408
Upper gastrointestinal tract; Gastrointestinal neoplasms; Iran
4.  Obesity and hypertension in an Iranian cohort study; Iranian women experience higher rates of obesity and hypertension than American women 
BMC Public Health  2006;6:158.
Once considered as the main public health problem in developed countries, obesity has become a major problem throughout the world and developing countries, like Iran, are joining the global obesity pandemic. We determined the prevalence of overweight, obesity, and hypertension in a large cohort of Iranians and compared age-adjusted rates with the rates in the US.
Golestan Cohort Study is a population-based study of 8,998 men and women, aged 35-81 years, from urban and rural areas. Anthropometric parameters were measured by interviewers. Prevalence rates were directly adjusted to the 2000 United States standard population.
The age-adjusted prevalence rates of overweight (BMI ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2) in this Iranian population were 62.2% and 28.0%, respectively. Both overweight and obesity were more common in women than men. Age-adjusted prevalence of overweight was significantly higher in Iranian women compared to the American women (68.6% vs. 61.6%), while the age-adjusted prevalence of obesity is closer in these two populations (34.9% vs. 33.2%). Iranian men—compared to American men—had significantly lower age-adjusted prevalence of overweight (53.7% vs. 68.8%) and obesity (16.2% vs. 27.5%). Age-adjusted prevalence of hypertension was higher in Iranian women than American women (35.7% vs. 30.5%). Diabetes mellitus was reported in 6.2% of participants. Mean waist-to-hip ratio (WHR) among women was 0.96. Smoking rates in men and women were 33.2% and 2.2%, respectively.
The prevalence of obesity, overweight, and hypertension in Iran is as high as the US. However, Iranian women are more obese than American women and Iranian men are less obese than their American counterparts. This discrepancy might be due to the low rate of smoking among Iranian women. Iranian women have higher mean WHR than what WHO has defined in 19 other populations.
PMCID: PMC1533819  PMID: 16784543

Results 1-4 (4)