No abstract

This study was conducted to estimate the socioeconomic costs of overweight and obesity in a sample of Korean adults aged 20 yr and older in 2005. The socioeconomic costs of overweight and obesity include direct costs (inpatient care, outpatient care and medication) and indirect costs (loss of productivity due to premature deaths and inpatient care, time costs, traffic costs and nursing fees). Hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, stroke, colon cancer and osteoarthritis were selected as obesity-related diseases. The population attributable fraction (PAF) of obesity was calculated from national representative data of Korea such as the National Health Insurance Corporation (NHIC) cohort data and the 2005 Korea National Health and Nutrition Examination Survey (KNHANES) data. Direct costs of overweight and obesity were estimated at approximately U$1,081 million equivalent (men: U$497 million, women: U$584 million) and indirect costs were estimated at approximately U$706 million (men: U$527 million, women: U$178 million). The estimated total socioeconomic costs of overweight and obesity were approximately U$1,787 million (men: U$1,081 million, women: U$706 million). These total costs represented about 0.22% of the gross domestic product (GDP) and 3.7% of the national health care expenditures in 2005. We found the socioeconomic costs of overweight and obesity in Korean adults aged 20 yr and older are substantial. In order to control the socioeconomic burden attributable to overweight and obesity, effective national strategies for prevention and management of obesity should be established and implemented.

No abstract

Human epidermal growth factor receptor 2 (HER2 or ErbB2) can be overexpressed, amplified and/or mutated in malignant tumors, and is a candidate for therapeutic targeting. However, molecular associations and clinical significances of these alterations were controversial in lung cancer. In this study, we investigated the frequency and clinicopathological significance of HER2 dysregulation in patients with lung adenocarcinoma. HER2 protein overexpression, gene amplification, and gene mutation were evaluated by immunohistochemistry (IHC), silver in situ hybridization, and direct sequencing, respectively. The H-scoring method and American Society of Clinical Oncology/College of American Pathologists breast cancer guidelines were used to interpret IHC results. Genetic analyses of EGFR and KRAS mutations, and of ALK and ROS1 rearrangements, were also performed. Of the 321 adenocarcinoma patients identified, HER2 overexpression (H-score ≥200) and gene amplification were found in 6 (1.9%) and 46 (14.3%), respectively. HER2 overexpression was correlated with papillary predominant histology; furthermore, it indicated poor overall survival and was an independent prognostic factor. HER2 amplification was associated with pleural invasion and showed a tendency towards shorter overall and disease-free survival. High-level gene amplification (HER2/CEP17 ratio ≥5 or copy number ≥10) was a poor prognostic factor for disease-free survival. HER2 mutations were detected in 6.7% (7 of 104) of driver oncogene-negative adenocarcinomas. Our study suggests that HER2 overexpression or amplification is a poor prognostic factor in lung adenocarcinoma, although the frequency of such events is low. Since molecular targeted agents are being tested in clinical trials, awareness of the specific HER2 status can influence the prognostic stratification and treatment of patients with molecularly defined subsets of lung adenocarcinoma.

Nuclear factor-κB (NF-κB) ligand (RANKL) was shown to induce osteoclast differentiation by increasing the expression of c-Fos, NFATc1 and TRAP. Salubrinal treatment to bone marrow macrophage (BMM) cells, however, significantly blocked NFATc1 expression and osteoclast differentiation by RANKL. Overexpression of NFATc1 further confirmed that NFATc1 is a key factor affected by salubrinal in osteoclast differentiation by RANKL. Unexpectedly, NFATc1 and c-Fos mRNA expressions were not affected by salubrinal, implicating that NFATc1 expression is regulated at a translational stage. In support of this, salubrinal increased the phosphorylation of a translation factor eIF2α, decreasing the global protein synthesis including NFATc1. In contrast, a phosphorylation mutant plasmid pLenti-eIF2α-S51A restored RANKL-induced NFATc1 expression and osteoclast differentiation even in the presence of salubrinal. Furthermore, knockdown of ATF4 significantly reduced salubrinal-induced osteoblast differentiation as evidenced by decreased calcium accumulation and lowered expressions of the osteoblast differentiation markers, alkaline phosphatase and RANKL in MC3T3-E1 osteoblast cells. Salubrinal treatment to co-cultured BMM and MC3T3-E1 cells also showed reduction of osteoclast differentiation. Finally, salubrinal efficiently blocked osteoporosis in mice model treated with RANKL as evidenced by elevated bone mineral density (BMD) and other osteoporosis factors. Collectively, our data indicate that salubrinal could affect the differentiation of both osteoblast and osteoclast, and be developed as an excellent anti-osteoporosis drug. In addition, modulation of ATF4 and NFATc1 expressions through eIF2α phosphorylation could be a valuable target for the treatment of osteoporosis.

Most cancer cells show resistance to ionizing radiation (IR)-induced cell death. Recently, Ki-Ras was reported to be responsible for the increased radioresistance. We report here that inhibition of IR-induced activaton of nuclear transcription factor kappa B (NF-kappaB) but not of either Akt or MAPK kinase (MEK), increased the radiosensitization of Ki-Ras transformed human prostate epithelial 267B1/K-ras cells. Proteosome inhibitor-1 (Pro1) reduced NF-kappaB activation, and this inhibition was accompanied by increased levels of cytoplasmic IkappaBalpha and p65/RelA. However, translocation of p50/NF-kappaB1 did not occur on exposure to IR, suggesting the cell-specific involvement of p50 in radiation signaling. Clonogenic cell survival and soft agar assays further confirmed the increased radiosensitivity of 267B1/K-ras cells by proteosome inhibition. In addition, proteosome inhibition enhanced the IR-induced degradation of apoptotic protein caspases 8 and 3, with the level of antiapoptotic protein Bcl-2 being unaffected, suggesting the involvement of an apoptotic process in IR-induced cell death of 267B1/K-ras cells. LY294002 and PD98059, specific inhibitors of phosphatidylinositol-3-kinase (PI3K) and MEK, respectively however, did not affect the radiosensitization. All these results suggest an application of blocking NF-kappaB activation pathway to the development of anticancer therapeutics in IR-induced radiotherapy of Ki-Ras-transformed cancer cells.

No abstract

BACKGROUND/OBJECTIVESChildhood obesity has increased in recent decades in Korea. This study was designed to examine differences in the eating habits, physical activity (PA), nutrition knowledge, and self-efficacy of children by obesity status.SUBJECTS/METHODSSubjects were 5th-grade children from 70 elementary schools in 17 cities nationwide. Two-stage stratified cluster sampling was employed. Survey questionnaire included items related to general characteristics, eating habits, PA, nutrition knowledge and self-efficacy. Excluding incomplete responses, 3,531 data were analyzed using SPSS. Subjects were categorized into overweight·obesity (OW) and normal weight (NW) groups based on body mass index percentiles for age by sex.RESULTSA total of 21.5% of subjects was overweight or obese. There were significant differences in gender, perceived stress, perception of body shape, body satisfaction, and interest in weight control between the OW and NW groups (P < 0.001). With respect to eating habits, the OW group ate breakfast (P < 0.05) and snacks (P < 0.01) less frequently, ate bigger meals (P < 0.001), and demonstrated less desirable behaviors during meals (P <0.05 in boys) compared to the NW group. The OW group participated in less PA than the NW group, especially boys. OW boys spent less time walking during weekdays (P < 0.05) or the weekend (P < 0.001), spent more time being sedentary during weekdays or the weekend (P < 0.001), and exercised a fewer number of days (P < 0.01). For girls, the OW group spent more time being sedentary during the weekend (P < 0.01) and exercised a fewer number of days by walking or bicycle riding (P < 0.05) than the NW group. Nutrition knowledge was not significantly different between the OW and NW groups. Self-efficacy (P < 0.01 in boys), especially PA self-efficacy (P < 0.01), was significantly lower in the OW than NW group.CONCLUSIONSThis study revealed differences in eating habits, PA, and self-efficacy between OW and NW children. Obesity management programs for children need to focus on increasing self-efficacy, modifying eating habits, and increasing PA.