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1.  Genome expression analysis by suppression subtractive hybridization identified overexpression of Humanin, a target gene in gastric cancer chemoresistance 
Background
In cancer cells, apoptosis is an important mechanism that influences the outcome of chemotherapy and the development of chemoresistance. To find the genes involved in chemoresistance and the development of gastric cancer, we used the suppression subtractive hybridization method to identify the genes that are overexpressed in gastric cancer tissues compared to normal gastric tissues.
Results
In the suppression subtractive hybridization library we constructed, the most highly overexpressed genes were humanin isoforms. Humanin is a recently identified endogenous peptide that has anti-apoptotic activity and has been selected for further study due to its potential role in the chemoresistance of gastric cancer. Upregulation of humanin isoforms was also observed in clinical samples by using quantitative real-time PCR. Among the studied isoforms, humanin isoform 3, with an expression level of 4.166 ± 1.44 fold, was the most overexpressed isoform in GC.
Conclusions
The overexpression of humanin in gastric cancer suggests a role for chemoresistance and provides new insight into the biology of gastric cancer. We propose that humanin isoforms are novel targets for combating chemoresistance in gastric cancer.
doi:10.1186/2008-2231-22-14
PMCID: PMC3896685  PMID: 24401285
Apoptosis; Chemoresistance; Gastric cancer; Suppression subtractive hybridization; Humanin
2.  Overexpression of FOXO3, MYD88, and GAPDH Identified by Suppression Subtractive Hybridization in Esophageal Cancer Is Associated with Autophagy 
To find genes involved in tumorigenesis and the development of esophageal cancer, the suppression subtractive hybridization (SSH) method was used to identify genes that are overexpressed in esophageal cancer tissues compared to normal esophageal tissues. In our SSH library, the forkhead box O3 (FOXO3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and myeloid differentiation primary response 88 (MYD88) genes were the most highly upregulated genes, and they were selected for further studies because of their potential role in the induction of autophagy. Upregulation of these genes was also observed in clinical samples using qRT-PCR. In addition, coexpression analysis of the autophagy-related genes Beclin1, ATG12, Gabarapl, PIK3C3, and LC3 demonstrated a significant correlation between the differentially overexpressed genes and autophagy. Autophagy is an important mechanism in tumorigenesis and the development of chemoresistance in cancer cells. The upregulation of FOXO3, GAPDH, and MYD88 variants in esophageal cancer suggests a role for autophagy and provides new insight into the biology of esophageal cancer. We propose that FOXO3, GAPDH, and MYD88 are novel targets for combating autophagy in esophageal cancer.
doi:10.1155/2014/185035
PMCID: PMC3910442  PMID: 24527027
3.  Predictors of Colorectal Cancer Survival in Golestan, Iran: A Population-based Study 
Epidemiology and Health  2013;35:e2013004.
OBJECTIVES
We aimed to investigate factors associated with colorectal cancer survival in Golestan, Iran.
METHODS
We used a population based cancer registry to recruit study subjects. All patients registered since 2004 were contacted and data were collected using structured questionnaires and trained interviewers. All the existing evidences to determine the stage of the cancer were also collected. The time from first diagnosis to death was compared in patients according to their stage of cancer using the Kaplan-Meir method. A Cox proportional hazard model was built to examine their survival experience by taking into account other covariates.
RESULTS
Out of a total of 345 subjects, 227 were traced. Median age of the subjects was 54 and more than 42% were under 50 years old. We found 132 deaths among these patients, 5 of which were non-colorectal related deaths. The median survival time for the entire cohort was 3.56 years. A borderline significant difference in survival experience was detected for ethnicity (log rank test, p=0.053). Using Cox proportional hazard modeling, only cancer stage remained significantly associated with time of death in the final model.
CONCLUSIONS
Colorectal cancer occurs at a younger age among people living in Golestan province. A very young age at presentation and what appears to be a high proportion of patients presenting with late stage in this area suggest this population might benefit substantially from early diagnoses by introducing age adapted screening programs.
doi:10.4178/epih/e2013004
PMCID: PMC3691365  PMID: 23807907
Colorectal cancer; Stage; Survival
4.  Goiter Frequency Is More Strongly Associated with Gastric Adenocarcinoma than Urine Iodine Level 
Journal of Gastric Cancer  2013;13(2):106-110.
Purpose
We designed our study to evaluate the hypothesis that gastric cancer is correlated with iodine deficiency or thyroid dysfunction.
Materials and Methods
We investigated the total body iodine reserve, thyroid function status and autoimmune disorder in 40 recently diagnosed gastric adenocarcinoma cases versus 80 healthy controls. The participants came from a region with high gastric cancer rate but sufficient iodine supply due to salt iodination. The investigation included urine iodine level, thyroid gland clinical and ultrasonographic examination, and thyroid function tests.
Results
Goiter was detected more frequently in the case group (P=0.001); such a finding, however, was not true for lower than normal urine iodine levels. The free T3 mean level was significantly lower in the case group compared to the control group (P=0.005).
Conclusions
The higher prevalence of goiter rather than low levels of urinary iodine in gastric adenocarcinoma cases suggests that goiter, perhaps due to protracted but currently adjusted iodine deficiency, is more likely to be associated with gastric adenocarcinoma compared to the existing iodine deficiency itself.
doi:10.5230/jgc.2013.13.2.106
PMCID: PMC3705130  PMID: 23844325
Stomach neoplasms; Goiter; Iodine; Thyroid function tests; Autoimmune diseases
5.  Modifiable Risk of Breast Cancer in Northeast Iran: Hope for the Future. A Case-Control Study 
Breast Care  2011;6(6):453-456.
Background
Breast cancer is the most common cancer in women. Its prevalence is increasing annually by 2%. The determination of modifiable risk factors has been the subject of various studies. The aim of this study was to determine risk factors of breast cancer in women in Golestan Province.
Patients and Methods
This case-control study was conducted among women with breast cancer recorded in the cancer registry system between 2004 and 2006 (n = 134), and their age-matched healthy neighbors (n = 133). Data were statistically analyzed.
Results
Age at marriage, menarche and pregnancy, breast feeding, positive family history, marital status, and educational level were not significantly correlated with risk of breast cancer, but age at menopause (< 46.6 years) was significantly correlated (95% confidence interval 1.15–7.37; p = 0.021). Live births, still births, and infant deaths were not significantly different between the 2 groups. For other variables, such as smoking history, no odds ratio was calculated.
Conclusion
Results show that there is no significant correlation between variables and risk of breast cancer in our population, except for age at menopause. A large cohort study is recommended.
doi:10.1159/000335203
PMCID: PMC3290010  PMID: 22419899
Breast cancer; Risk factors; Golestan; Case-control study
6.  None-endoscopic Screening for Esophageal Squamous Cell Carcinoma- A Review 
Esophageal cancer (EC) is the eighth most common cancer and sixth most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. ESCC develops by progression from premalignant lesions, which are called esophageal squamous dysplasia (ESD). Prevention is the most effective strategy for controlling this disease. Generally, two methods may be defined for ESCC prevention. The aim of the first preventive method is to prevent the initiation of ESD by avoiding the known risk factors, or primary prevention. Secondary prevention focuses on detection of the disease in its early curable stage, thus preventing its progression into advanced stages. Endoscopy with iodine staining and biopsy is the diagnostic choice for ESD. However it is invasive and expensive, and not accepted by asymptomatic ESD cases. Therefore, it is necessary to find a non-endoscopic screening method. Despite the large number of studies conducted worldwide, no approved method has been developed for ESCC screening. Regarding the multi-factorial nature of ESCC, it is proposed that the use of a combination of various criteria, such as cytological examination, risk factors, genetic alteration, and molecular markers may result in the development of a comprehensive and effective ESCC screening program.
PMCID: PMC4017690  PMID: 24829644
Esophageal squamous cell carcinoma; Screening; Non-endoscopic; Review
7.  The Role of IL-6 for Predicting Neonatal Sepsis: A Systematic Review and Meta-Analysis 
Iranian Journal of Pediatrics  2011;21(4):411-417.
Objective
Neonatal sepsis (NS) is a common and life-threatening disorder in infants. Previous studies showed that interleukin-6 (IL-6) may be a valid non-invasive and rapid method for diagnosis of NS. We conducted this review to assess the validity of IL-6 for predicting NS.
Methods
This was a systematic review with meta-analysis. Embase, Medline and Web of Science databases were searched between January 1990 and December 2009. The search terms used were “cytokine”, “neonate”, “sepsis” and “interleukin-6". We used standard methods recommended for meta analyses of diagnostic test evaluations. The analysis was based on a summary ROC (SROC) curve. Meta-regression analysis was used to assess the effects of some confounding factors on the results of meta-analysis. Potential presence of publication bias was tested using funnel plots and the Egger test.
Findings
Meta-analysis was performed on 13 publications including 353 infants with sepsis and 691 control infants. The pooled sensitivity and specificity of IL-6 was 0.79 and 0.84, respectively. The maximum joint sensitivity and specificity (i.e., the Q value) in SROC curve was 0.82 and the area under curve (AUC) was 0.89 (95% CI: 0.84-0.94). Meta-regression analysis showed that the diagnostic accuracy of IL-6 was not affected by confounding variables. The evaluation of publication bias showed that the Egger test was not significant (P=0.07).
Conclusion
IL-6 seems to be a valid marker for predicting NS. It may be considered for early diagnosis of sepsis in neonatal care units.
PMCID: PMC3446138  PMID: 23056824
Interlukin-6; Cytokines; Sepsis; Neonate; Meta-analysis
9.  Incidence of Childhood Cancers in Golestan Province of Iran 
Iranian Journal of Pediatrics  2010;20(3):335-342.
Objective
This paper presents the incidence rates of childhood cancers using the data obtained from Golestan population based cancer registry (GPCR) between 2004 and 2006.
Methods
GPCR registers only primary cancers based on standard protocols of the international association of cancer registries (IACR). We collect data on newly diagnosed (incident) cancer cases from all public and private diagnostic and therapeutic centers of the whole province. CanReg-4 software was used for data entry and analysis.
Findings
Totally 5076 cancer cases (all ages) were diagnosed in GPCR between 2004 and 2006. Of these, 139 (2.74 %) were children (aged 0–14 years) with mean (±SD) age of 8.06 (±4.48) years. The age standardized incidence rates for childhood cancer were 119.8 and 78.3 per 1000000 person-years in male and female children, respectively. Leukemia was the most common childhood cancer in Golestan province of Iran. Lymphomas and central nervous system tumors were the second and third ones, respectively.
Conclusion
The incidence rates of childhood cancers were relatively high in Golestan province of Iran. So, controlling of childhood cancers should be mentioned as an important issue in health policy making in this area.
PMCID: PMC3446043  PMID: 23056726
Childhood; Cancer; Population; Cancer registry; Iran

Results 1-9 (9)