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.     

Can we rely on public data as a source of information for cancer registry in developing countries?

BACKGROUND/AIMS: Although a "hospital-based cancer registry" is important in improving patient care, a "population-based cancer registry" with emphasis on epidemiology is important in allocating health care resources and prioritizing public health programs. Because of its reliance on retrieved clinical and para-clinical documents, there is some limitation in registering all cancer incidents in this system, especially in developing countries. In this study we examined the possibility of using public data as a complementary source of information for recording cancers in a population-based cancer registry. METHODS: Along with the annual census in rural areas, a survey was performed in Golestan province in March 2004 to identify public awareness about cancer incidents in the community. Individuals were questioned about history of cancer in their close relatives during the last two years. Those who reported cancer in their relatives were also asked to name the main organ of involvement. A similar list was retrieved from the cancer registry at the Ministry of Health in Gorgan, and cases with upper GI (esophagus and gastric) cancer diagnosis from 21 March 2002 through 20 March 2004 were selected for this study. Finally, these two lists were compared for examining accuracy of the collected data. RESULTS: We included 137 cases in our study with rural residence and known addresses. Only 35 (25.5%) cases were reported by the relatives and among them only 20 (57.1%) relatives correctly reported the tumor location. Although we found a difference in accurate reporting of cancer incidents by year of diagnosis (more correct cases reported during the second versus the first year), the difference was not statistically significant between the two years. CONCLUSION: In this study, we examined the possibility of using public awareness about cancer incidents as a complementary source of information for a population-based cancer registry. We found that this approach is not ideal for reducing limitations. Therefore, we recommend a nationwide cancer registry to record all cancer-related information at the time of diagnosis. This strategy will reduce the need for performing retrospective surveys in collecting cancer-related information.     

Modifiable Risk of Breast Cancer in Northeast Iran: Hope for the Future. A Case-Control Study

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.     

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.     

The effect of granulocyte colony‐stimulating factor dose and administration interval after allogeneic hematopoietic cell transplantation on early engraftment of neutrophil and platelet

BackgroundHematopoietic stem cell transplantation (HSCT) is one of the treatments for hematologic malignancies. Numerous factors affect the HSCT outcome. The purpose of this study was to investigate the effect of post‐HSCT administration of granulocyte colony‐stimulating factor (post‐G‐CSF) on early neutrophil and platelet engraftment in allogeneic HSCT (allo‐HSCT).Material & methodsThe study was performed on 76 patients diagnosed with AML and ALL. All patients underwent allo‐HSCT at Taleghani stem cell transplantation center, Tehran, Iran, from February 2016 to December 2018. Chemotherapy regimens based on patients'' conditions were selected between myeloablative and reduced‐intensity regimens.ResultsStatistical analysis revealed that the number of administered G‐CSF units after HSCT was a time‐dependent variable. Statistical analysis before day +11 reported that patients who received G‐CSF <14 units had three times better early neutrophil engraftment than those with G‐CSF ≥14 (CI 95%, AHR = 3.03, p:0.002). CD3+ cells count <318.5 × 10⁶/kg was associated with fast platelet engraftment (CI 95%, AHR 2.28, p:0.01).ConclusionIn this study, post‐G‐CSF stimulation was associated with early engraftment in a time‐ and dose‐dependent manner. Administration of G‐CSF beyond 14 units resulted in adverse effects on neutrophil early engraftment. It also appeared that with a reduction in CD3+ cell counts, the likelihood of GVHD decreases, and platelet engraftment occurs earlier. Further investigations in the future are required to determine the factors affecting the process of early engraftment.     

Interaction of HLA-DRB1*1501 allele and TNF-alpha -308 G/A single nucleotide polymorphism in the susceptibility to multiple sclerosis

Multiple sclerosis is a multifactorial disorder with complex genetic basis. It is believed that genes encoding HLA molecule and cytokines are involved in the pathogenesis of MS. In this study, we have evaluated the impact of HLA-DRB1*1501 allele and TNF-alpha -308 G/A single nucleotide polymorphism, and their interaction, in the susceptibility to MS in Iranian population. Genomic DNA samples were prepared from whole blood of 366 MS Patients and 414 control subjects. The genotypes were determined by SSP-PCR method. Frequency of alleles and genotypes were compared between the two groups by using Fisher's exact test. HLA-DRB1*1501 allele was more frequent among patients (OR=1.57, P=0.0026). TNF-α -308 G allele and G/G genotype had higher frequency among MS patients than control subjects (G vs. A: OR=1.26, P<0.05); G/G vs. A/A: OR=4.59, P=0.0003). The odds ratio was higher among HLA-DRB1*1501 positive individuals. Co-existence of TNF G and HLA-DRB1*1501 alleles showed higher prevalence among MS patients (OR=7.07, P=0.0007). Our results have shown that HLA-DRB1*1501 allele and TNF-α -308 G/A polymorphism are associated with the risk of multiple sclerosis in Iranian population. We also observed an interaction between these two loci that support the role of HLA alleles and cytokine genes and gene-gene interaction in the development and pathogenesis of MS.     

Effect of intrauterine morphine sulfate exposure on cerebellar histomorphological changes in neonatal mice

Neurotoxic effects of morphine sulfate in adult cerebellar cortex and neonatal cerebral cortex have been studied in animal models. This study was done to determine the neurotoxic effects of prenatal morphine exposure on the histo-morphological changes of cerebellar cortical layer and Purkinje cells in mice neonates. In this experimental study 30 female mice were randomly allocated into cases and controls. In the case group, animals received morphine sulfate 10 mg/kg/body weight intraperitoneally for 7 days. After mating, dams received morphine sulfate 10 mg/kg/body weight intraperitoneally for 20 days of gestation. Animals in the control group received normal saline. On the day of delivery (P0), the cerebella of six neonates for each group were removed and stained with cresyl violet. Quantitative computer-assisted morphometric study was done on the cortical layer of the cerebellum. Morphine exposure caused a non-significant increase in fetal weight in the case group. Purkinje cells in cases were decreased in comparison with controls (p < 0.05). Histomorphometric examination revealed that the thickness of Purkinje and internal granular layers of the cerebellar cortex decreased in the morphine-exposed group (p < 0.05). This study revealed that morphine administration before and during pregnancy can cause Purkinje cell loss and reduction of thickness of the Purkinje and internal granular layer of the cerebellar cortex and size of Purkinje cells in neonatal mice.     

Midterm outcomes of penetrating keratoplasty after cultivated oral mucosal epithelial transplantation in chemical burn

Purpose

To evaluate the midterm outcomes of penetrating keratoplasty (PKP) after cultivated oral mucosal epithelial transplantation (COMET) in patients with bilateral total limbal stem cell deficiency (LSCD) due to chemical burn.