An Essential Regulatory Role of Downstream of Kinase-1 in the Ovalbumin-Induced Murine Model of Asthma

The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population

<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population.</p> <p>Methods</p> <p>We conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis.</p> <p>Results</p> <p>The MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, <it>P </it>= 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, <it>P </it>= 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer.</p> <p>Conclusions</p> <p>The T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.</p

Recent Trends in Prostate Cancer Incidence by Age, Cancer Stage, and Grade, the United States, 2001–2007

Objective. To examine prostate cancer trends by demographic and tumor characteristics because a comprehensive examination of recent prostate cancer incidence rates is lacking. Patients and Methods. We described prostate cancer incidence rates and trends using the 2001–2007 National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program data (representing over 93% of US population). Because of coding changes in cancer grade, we restricted analysis to 2004–2007. We conducted descriptive and trend analyses using SEER*Stat. Results. The overall prostate cancer incidence rate was stable from 2001 to 2007; however, rates significantly increased among men aged 40–49 years (APC = 3.0) and decreased among men aged 70–79 years (APC = 2.3), and 80 years or older (APC = −4.4). About 42% of localized prostate cancers diagnosed from 2004 to 2007 were poorly differentiated. The incidence of poorly differentiated cancer significantly increased among localized (APC = 8.0) and regional stage (APC = 6.1) prostate cancers during 2004–2007. Conclusions. The recent trend in prostate cancer incidence was stable but varied dramatically by age. Given the large proportion of poorly differentiated disease among localized prostate cancers and its increasing trend in more recent years, continued monitoring of prostate cancer incidence and trends by demographic and tumor characteristics is warranted

Metabolic Risk Profile and Cancer in Korean Men and Women

Objectives: Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. Methods: We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. Results: A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. Conclusions: The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women

The Economic Burden of Cancers Attributable to Metabolic Syndrome in Korea

Objectives: Metabolic syndrome is an important etiologic factor in the development of certain types of cancers. The economic cost of the treatment of cancer has been steadily increasing. We therefore estimated the economic burden of cancers attributable to metabolic syndrome in Korea. Methods: We reviewed metabolic syndrome-related cancers and relative risk and then calculated population attributable fractions. We analyzed insurance claims data for metabolic syndrome-related cancers in 2012 in order to estimate the direct costs associated with these cancers, including hospitalization, outpatient visits, transportation costs, and caregivers’ costs as well as indirect costs such as loss of productivity due to cancer treatment and premature death. Results: In 2012, 18 070 patients in Korea had cancers attributable to metabolic syndrome. The economic burden was USD 199.8 million and the direct and indirect costs were USD 124.5 million and USD 75.3 million, respectively. Conclusions: We estimated the economic burden of cancers attributable to metabolic syndrome in Korea and the efforts are necessary to reduce this burden