Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.
Objectives: Inflammatory bowel disease (IBD) is chronic inflammatory disorders of the intestines. Due to limitation of conventional treatment including steroids, herbal medicines have emerged as possible therapeutic options for IBD. The purpose of the current study was to investigate the therapeutic and prophylactic effects and mechanisms of Zostera Marina water extract (ZME) on DSS-induced colitis. Methods: Colitis was induced by DSS in Balb/c mice. In pre-treatment setting, ZME was administered 7 days before DSS treatment and in co-treatment setting, ZME was simultaneously administrated with DSS treatment. In both settings, ZME 100, 300 and 1000 mg/kg were orally administered twice a day, respectively. Mice weight and clinical findings were measured daily. Colon length, macroscopic findings and histological damages of colon mucosa were assessed at the end of experiments. The levels of cytokines including TNF-${\alpha}$, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, IL-10 and IL-17 were measured by Biometric Multiplex Cytokine Profiling method. Results: In a dose dependent manner, ZME significantly inhibited the colon shortening, and improved macroscopic score and histological score. However, there were insignificant changes on inhibition of weight loss and improvement of clinical score. There were no significant differences of effects between co-treatment and pre-treatment settings. ZME 300 and 1000 mg/kg groups significantly inhibited IFN-${\gamma}$. Only ZME 1000 mg/kg group significantly inhibited TNF-${\alpha}$, IL-$1{\beta}$ and IL-6. Conclusions: The current results show the possibility of therapeutic use and its prophylactic application of ZME on inflammatory bowel diseases. Future studies for targeted mechanisms of ZME are needed.
Crohn's disease (CD) is a chronic inflammatory bowel disease with multifactorial causes including environmental and genetic factors. Several studies have demonstrated that the organic cation/carnitine transporter 1 (OCTN1) non-synonymous variant L503F is associated with susceptibility to CD. However, it was reported that L503F is absent in Asian populations. Previously, we identified and functionally characterized genetic variants of the OCTN1 promoter region in Koreans. In that study, four variants demonstrated significant changes in promoter activity. In the present study, we determined whether four functional variants of the OCTN1 promoter play a role in the susceptibility to or clinical course of CD in Koreans. To examine it, the frequencies of the four variants of the OCTN1 promoter were determined by genotyping using DNA samples from 194 patients with CD and 287 healthy controls. Then, associations between genetic variants and the susceptibility to CD or clinical course of CD were evaluated. We found that susceptibility to CD was not associated with OCTN1 functional promoter variants or haplotypes showing altered promoter activities in in vitro assays. However, OCTN1 functional promoter haplotypes showing decreased promoter activities were significantly associated with a penetrating behavior in CD patients (HR=2.428, p=0.009). Our results suggest that the OCTN1 functional promoter haplotypes can influence the CD phenotype, although these might not be associated with susceptibility to this disease.
The Korean diet, including breakfast, is becoming more Western, which could increase the risk of metabolic syndrome. Our aim was to assess whether breakfast patterns are associated with risk for metabolic syndrome in Korean adults. The study subjects (n=371; 103 men, 268 women) were employees of Jaesang Hospital in Korea and their acquaintances, and all subjects were between 30 and 50 years old. The data collected from each subject included anthropometric measurements, three-day food intake, blood pressure (BP) and blood analyses. The three breakfast patterns identified by factor analysis were "Rice, Kimchi and Vegetables", "Potatoes, Fruits and Nuts" and "Eggs, Breads and Processed meat". The "Rice, Kimchi and Vegetables" pattern scores were positively correlated with systolic (SBP) and diastolic blood pressure (DBP) measurements in men (P<0.05) and with serum triglyceride (TG) levels in women (P<0.05). The "Eggs, Breads and Processed meat" pattern scores correlated positively with weight, body mass index (P<0.05) and serum TGs (P<0.01) in men. The "Potatoes, Fruits and Nuts" pattern was associated with lower risk of elevated BP (OR 0.49, 95% CI 0.28-0.88) and fasting glucose levels (OR 0.51, 95% CI 0.26-1.00). In contrast, the "Eggs, Breads and Processed meat" pattern was associated with increased risk of elevated TGs (OR 2.06, 95% CI 1.06-3.98). Our results indicate that reducing the consumption of eggs, western grains and processed meat while increasing fruit, nut and vegetable intake for breakfast could have beneficial effects on decreasing metabolic syndrome risk in Korean adults.
Consumption of a diet consistent with dietary guidelines is believed to have a beneficial effect on the prevention of chronic diseases and the promotion of general health. This study was conducted to explore the relationship between adherence to the Korean Food Guidance System (KFGS), which was based on the 2010 revised KDRIs, and the risk of metabolic abnormalities. Five hundred and ninety-six Korean adults between 30 and 59 years of age were recruited by advertisement to the Bundang Jesaeng General Hospital (BJGH), and those not taking regular medications and without diagnoses of fulminant disease were included. Data were collected on anthropometric measurements, diagnostic parameters for metabolic syndrome (MetS), and 3-day dietary intakes from individuals in the study. The number of servings consumed from each food group was compared to the KFGS recommended servings for each of the 6 food groups. Poor adherence to the recommendations for servings of milk and dairy products (OR: 2.038, 1.128-3.682) was associated with a higher risk of MetS, and poor adherence to the guidelines for fruit consumption (OR: 1.849, 1.027-3.329) was associated with a higher risk for the existence an elevated waist circumference. Conversely, the consumption of meat, fish, eggs, and beans above the recommended number of servings was associated with a lower risk of having an elevated waist circumference (OR: 0.523, 0.288-0.950), and the consumption of vegetables above the recommended number of servings was associated with a reduced risk of having elevated fasting glucose (OR: 0.533, 0.298-0.954). These results suggest that adherence to the KFGS guidelines helps to prevent the development of MetS, but this association needs to be confirmed by prospective studies.
Mutations in the rdxA gene had been reported to be associated with metronidazole resistance in Helicobacter pylori. In this study, sensitivity to metronidazole, RAPD profiles, and DNA sequences of the rdxA gene of 32 local H. pylori isolates were analyzed. Of these, 13 were found to be resistant, while 19 were sensitive to metronidazole. Among the 32 isolates, 10 were paired isolates from the antrum and body of the stomach of individual patients. Interestingly, the RAPD profiles of isolates from individual patients were distinctly different from each other, whereas paired isolates from the same patient were identical regardless of their sensitivities to metronidazole. DNA sequences of the rdxA gene of all 32 isolates showed 95% to 97% homology when compared with the HP0954 locus of H. pylori 26695 genome. From the 19 metronidazole-sensitive strains, 10 (with $MIC{\le}0.5\;\mu\textrm{g}/ml$ metronidazole) were selected and induced to become metronidazole resistant by sequentially passaging through serial 2-fold increasing concentrations of metronidazole. Nine of the 10 induced paired isolates showed mutations in the rdxA sequences which resulted in truncated protein or changes in the translated amino acid sequences. However, the changes did not occur at any specific site in the DNA or amino acid sequences of the rdxA gene of all the isolates analyzed. The results show that the rdxA gene cannot be a definitive marker for metronidazole resistance in H. pylori isolates of an Asian population, and that other factors may contribute to resistance to metronidazole.
Background: The aim of this study was to investigate differences of miRNA-34a expression in benign and malignant colorectal lesions. Materials and Methods: Samples of cancer, paraneoplastic tissues and polyps were selected and total RNA was extracted by conventional methods for real-time PCR to detect the miRNA-34a expression. In addition, the LOVO colorectal cancer cell line was cultured, treated with the demethylating agent 5-azacytidine and screened for differentially expressed miRNA-34a. Results: After the drug treatment, the miRNA-34a expression of colorectal cancer cell line LOVO was increased and real-time PCR showed that levels of expression in both cell line and colorectal cancer tissues were low, as compared to paraneoplastic tissue (p<0.05). Polyps tissues had significantly higher expression than paraneoplastic and colorectal cancer samples (p<0.05). Conclusions: miRNA-34a-5p may play a role as a tumor suppressor gene in colorectal cancer, with involvement of DNA methylation.
Background: To investigate the effects of ASMase mediated endothelial cell apoptosis in multiple hypofractionated irradiations in CT26 tumor bearing mice. Materials and Methods: Thirty-five CT26 tumor bearing mice were subjected to single ionizing radiation (IR) of 0, 3, 6, 9, 12, 15, 18 Gy. Eight hours after IR, the mice were sacrificed and tumor tissues were used for CD31 immunohistochemistry staining, TUNEL and CD31 double staining, ASMase activity assay. Then 6 and 12 Gy were chosen for multiple hypofractionated IR experiments according to the above results. Each time after IR, 5 mice were sacrificed and assayed as above. Results: The ASMase activities were increased significantly after a single IR of 12 Gy or higher which was accompanied with remarkable increased endothelial cell apoptosis and decreased MVD. For 6 Gy which was not high enough to trigger ASMase activation, after 2 or more times of IR, the ASMase activities were significantly increased accompanied with remarkable increased endothelial cell apoptosis and decreased MVD. While for 12 Gy, after 2 or more times of IR, the ASMase activities and endothelial cell apoptosis rates were maintained without remarkable increase; however, the MVD was significantly decreased. What's more, the cancer cell apoptosis rates were significantly increased after multiple IR for both 6 Gy and 12 Gy. Conclusions: ASMase mediated endothelial cell apoptosis may play an important role in the process of multiple hypofractionated IR for CT26 colorectal carcinoma.
Zeinalian, Mehrdad;Hashemzadeh-Chaleshtori, Morteza;Akbarpour, Mohammad Javad;Emami, Mohammad Hassan
Asian Pacific Journal of Cancer Prevention
/
v.16
no.11
/
pp.4647-4652
/
2015
Background: Colorectal cancer (CRC) is becoming one of the most complicated challenges of human health, particularly in developing countries like Iran. In this paper, we try to characterize CRC cases diagnosed < age 50 at-risk for Lynch syndrome within central Iran. Materials and Methods: We designed a descriptive retrospective study to screen all registered CRC patients within 2000-2013 in Poursina Hakim Research Center (PHRC), a referral gastroenterology clinic in central Iran, based on being early-onset (age at diagnosis ${\leq}50years$) and Amsterdam II criteria. We calculated frequencies and percentages by SPSS 19 software to describe clinical and family history characteristics of patients with early-onset CRC. Results: Overall 1,659 CRC patients were included in our study of which 413 (24.9%) were ${\leq}50years$ at diagnosis. Of 219/413 successful calls 67 persons (30.6%) were reported deceased. Family history was positive for 72/219 probands (32.9%) and 53 families (24.2%) were identified as familial colorectal cancer (FCC), with a history of at-least three affected members with any type of cancer in the family, of which 85% fulfilled the Amsterdam II Criteria as hereditary non-polyposis colorectal cancer (HNPCC) families (45/219 or 20.5%). Finally, 14 families were excluded due to proband tumor tissues being unavailable or unwillingness for incorporation. The most common HNPCC-associated extracolonic-cancer among both males and females of the families was stomach, at respectively 31.8 and 32.7 percent. The most common tumor locations among the 31 probands were rectum (32.3%), sigmoid (29.0%), and ascending colon (12.9%). Conclusions: Given the high prevalence of FCC (~1/4 of early-onset Iranian CRC patients), it is necessary to establish a comprehensive cancer genetic counseling and systematic screening program for early detection and to improve cancer prognosis among high risk families.
Background: Gallbladder cancer (GBC) is a rare but highly invasive malignancy characterized by poor survival. In a national cancer survey, the age-standardized incidence rate of GBC was highest in Jeju Island among the 15 provinces in South Korea. The aim of this descriptive epidemiological study was to suggest the modifiable risk factors for this rare malignant disease in Jeju Island by performing an age-sex-matched case-control study. Materials and Methods: The case group included patients diagnosed with GBC at the Department of Internal Medicine of Cheju Halla General Hospital, Jeju, South Korea, within the 5-year study period. The control group consisted of age-sex-matched subjects selected from among the participants of the health promotion center at the same institute and in the same period. We compared 78 case-control pairs in terms of clinical variables such as histories of hypertension, diabetes, vascular occlusive disorders, alcohol and smoking consumption, obesity, and combined polypoid lesions of the gallbladder (PLG) or gallstone diseases (GSDs). Results: Among the relevant risk factors, alcohol consumption, parity ${\geq}2$, PLG, and GSDs were significant risk factors in the univariate analysis. PLG (p < 0.01; OR, 51.1; 95% confidence interval [CI], 2.98-875.3) and GSD (p < 0.01; OR, 54.9; 95% CI, 3.00-1001.8) were associated risk factors of GBC in the multivariate analysis with the conditional logistic regression model. However, we failed to find any correlation between obesity and GBC. We also found a negative correlation between alcohol consumption history and GBC in the multivariate analysis (p < 0.01; OR, 0.06; 95% CI, 0.01-0.31). Conclusions: These results suggest that combined PLG and GSDs are strongly associated with the GBC in Jeju Island and mild to moderate alcohol consumption may negatively correlate with GBC risk.
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