No abstract available.
Animals ; Rats*

PURPOSE: Recently, the use of radiosurgery as a local therapy in patients with early stage non-small cell lung cancer has become favored over surgical resection. To evaluate the efficacy of radiosurgery, we analyzed the results of stereotactic body radiosurgery in patients with primary or recurrent non-small cell lung cancer. MATERIALS AND METHODS: We reviewed medical records retrospectively of total 24 patients (28 lesions) with non-small cell lung cancer (NSCLC) who received stereotactic body radiosurgery (SBRT) at Inha University Hospital. Among the 24 patients, 19 had primary NSCLC and five exhibited recurrent disease, with three at previously treated areas. Four patients with primary NSCLC received SBRT after conventional radiation therapy as a boost treatment. The initial stages were IA in 7, IB in 3, IIA in 2, IIB in 2, IIIA in 3, IIIB in 1, and IV in 6. The T stages at SBRT were T1 lesion in 13, T2 lesion in 12, and T3 lesion in 3. 6MV X-ray treatment was used for SBRT, and the prescribed dose was 15~60 Gy (median: 50 Gy) for PTV1 in 3~5 fractions. Median follow up time was 469 days. RESULTS: The median GTV was 22.9 mL (range, 0.7 to 108.7 mL) and median PTV1 was 65.4 mL (range, 5.3 to 184.8 mL). The response rate at 3 months was complete response (CR) in 14 lesions, partial response (PR) in 11 lesions, and stable disease (SD) in 3 lesions, whereas the response rate at the time of the last follow up was CR in 13 lesions, PR in 9 lesions, SD in 2 lesions, and progressive disease (PD) in 4 lesions. Of the 10 patients in stage I, one patient died due to pneumonia, and local failure was identified in one patient. Of the 10 patients in stages III-IV, three patients died, local and loco-regional failure was identified in one patient, and regional failure in 2 patients. Total local control rate was 85.8% (4/28). Local recurrence was recorded in three out of the eight lesions that received below biologically equivalent dose 100 Gy10. Among 20 lesions that received above 100 Gy10, only one lesion failed locally. There was a higher recurrence rate in patients with centrally located tumors and T2 or above staged tumors. CONCLUSION: SBRT using a CyberKnife was proven to be an effective treatment modality for early stage patients with NSCLC based on high local control rate without severe complications. SBRT above total 100 Gy10 for peripheral T1 stage patients with NSCLC is recommended.
Carcinoma, Non-Small-Cell Lung ; Follow-Up Studies ; Humans ; Lung ; Medical Records ; Pneumonia ; Radiosurgery ; Recurrence ; Retrospective Studies

Regular exercise and a certain level of physical activity reduce the mortality rate in the elderly. The purpose of this study was to investigate the effect of physical activity on the prevention of fracture in the middle aged or older in Korea. The basic data are based on the Ansan and Ansung community cohort studies of the Korean Genome and Epidemiology Study conducted by the Korea Centers for Disease Control and Prevention in 2001, and the fracture data from the third survey in 2005 to the sixth survey in 2011. The physical activity of the aged in the 40s was mostly distributed in the World Health Organization (WHO) recommended range of 7.5 to 30.0 metabolic equivalent·hr/wk, and the activity was gradually divided into the low and high groups in the 50s and 60s. In the 60s, the risk of fracture was reduced to 0.63 times compared to that of the 50s when physical activity was the recommended level (odds ratio, 0.63; p<0.001). For Korean adults, there was no significant difference in fracture incidence according to the amount of physical activity in the middle-aged people. However, for the elderly aged 60 and over, the risk of fracture decreased when the WHO recommended level of activity was performed, and the risk increased when less or more activities were performed.
Adult* ; Aged ; Centers for Disease Control and Prevention (U.S.) ; Cohort Studies* ; Epidemiology ; Fractures, Bone ; Genome ; Gyeonggi-do ; Humans ; Incidence ; Korea ; Middle Aged ; Mortality ; Motor Activity* ; World Health Organization

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1alpha activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1alpha. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1alpha expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1alpha was important for MSC survival under hypoxic conditions.
Cell Survival ; Cobalt ; Gene Expression Regulation/*physiology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Mesenchymal Stromal Cells/drug effects/metabolism/*physiology ; MicroRNAs/*metabolism ; Oxygen/pharmacology ; *Oxygen Consumption ; RNA, Small Interfering/metabolism

Purpose: The purpose of this study was to investigate the clinicopathologic characteristics of young gastric cancer patients and analyze the risk factors for stage underestimation and survival. Methods: Relevant data of 5029 patients who underwent surgery for gastric cancer at Seoul National University Bundang Hospital between 2003 to 2014 were collected. Patients were divided based on age (younger group and older group). Clinical stages were compared to pathologic stages for accuracy, and risk factors for underestimation were analyzed using univariate and multivariate analysis regression. Overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Results: A total of 4396 patients were eligible for inclusion. The younger group was an independent risk factor for nodal metastasis (RR=1.44, 95% CI 1.06~1.95) and an independent risk factor for clinical N-stage underestimation (RR=1.50, 95% CI=1.14~1.98). However, there was no significant difference in 5-year cancer-specific survival for both age groups (92.2% vs 90.2%, p=0.306). Conclusion In conclusion, intra-operative investigation of T-stage with standard operation should be done in young gastric cancer patients as they have a higher incidence of lymph node metastasis, with greater frequency of stage underestimation.

Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH.
Animals ; DNA Methylation/drug effects ; Drug Discovery/methods ; *Epigenesis, Genetic/drug effects ; Genetic Therapy/methods ; Humans ; Hypertension, Pulmonary/*genetics/therapy ; MicroRNAs/*genetics

Lithium is the drug of choice for treating bipolar affective disorders. However, it has a narrow therapeutic index and acute and chronic toxicity can occur in patients with chronic ingestion. Chronic toxicity commonly presents as nephrogenic diabetes insipidus or thyroid dysfunction. Neurologic symptoms such as apathy, hyperreflexia, or clonus can also occur in acute toxicity. However, it rarely causes peripheral neuropathy. We experienced a case of lithium-induced peripheral polyneuropathy who had already nephrogenic diabetes insipidus and chronic kidney disease during 25 years of lithium ingestion due to bipolar disorder.
Apathy ; Bipolar Disorder ; Diabetes Insipidus ; Diabetes Insipidus, Nephrogenic* ; Eating ; Humans ; Lithium ; Mood Disorders ; Neurologic Manifestations ; Peripheral Nervous System Diseases ; Polyneuropathies* ; Reflex, Abnormal ; Renal Insufficiency, Chronic ; Thyroid Gland ; Upper Extremity*

PURPOSE: This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. MATERIALS AND METHODS: The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. RESULTS: A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. CONCLUSION: The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.
Breast Neoplasms* ; Breast* ; Drug Therapy ; Education* ; Educational Status ; Humans ; Mastectomy, Segmental ; Multivariate Analysis ; Prognosis ; Survival Analysis

Butylated hydroxyanisole (BHA) is a synthetic phenolic compound consisting of a mixture of two isomeric organic compounds: 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. We examined the effect of BHA against hydrogen peroxide (H2O2)-induced apoptosis in primary cultured mouse hepatocytes. Cell viability was significantly decreased by H2O2 in a dose-dependent manner. Additionally, H2O2 treatment increased Bax, decreased Bcl-2, and promoted PARP-1 cleavage in a dose-dependent manner. Pretreatment with BHA before exposure to H2O2 significantly attenuated the H2O2-induced decrease of cell viability. H2O2 exposure resulted in an increase of intracellular reactive oxygen species (ROS) generation that was significantly inhibited by pretreatment with BHA or N-acetyl-cysteine (NAC, an ROS scavenger). H2O2-induced decrease of cell viability was also attenuated by pretreatment with BHA and NAC. Furthermore, H2O2-induced increase of Bax, decrease of Bcl-2, and PARP-1 cleavage was also inhibited by BHA. Taken together, results of this investigation demonstrated that BHA protects primary cultured mouse hepatocytes against H2O2-induced apoptosis by inhibiting ROS generation.
Animals ; Apoptosis/*drug effects ; Butylated Hydroxyanisole/chemistry/*pharmacology ; Cell Survival/drug effects ; Cells, Cultured ; Hepatocytes/*drug effects ; Hydrogen Peroxide/*toxicity ; Male ; Mice ; Mice, Inbred ICR ; Molecular Structure

PURPOSE: Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27(Kip1) and retinoblastoma protein (RB). However, the upstream signaling mechanisms associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase pathway is the central regulator of cell growth and proliferation, and increases cell proliferation by inhibiting the activities of p27(Kip1) and retinoblastoma protein (RB). Therefore, we hypothesized in this study that rosiglitazone inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K signaling pathway. MATERIALS and METHODS: Rat aortic smooth muscle cells (RAoSMCs) were treated with 10microM of rosiglitazone 24 hours before the addition of insulin as a mitogenic stimulus. Western blot analysis was performed to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR-P70S6K signaling pathway. Carotid balloon injury was also performed in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3 mg/kg of rosiglitazone. RESULTS: Western blot analysis demonstrated significant inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex. CONCLUSION: The inhibitory effect of rosiglitazone on RAoSMC proliferation in vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.
Animals ; Cell Proliferation/drug effects ; Cells, Cultured ; Cytoprotection/drug effects ; Enzyme Activation/drug effects ; Insulin/*pharmacology ; Male ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Muscle, Smooth, Vascular/drug effects/*metabolism ; Myocytes, Smooth Muscle/drug effects/*metabolism ; Phosphorylation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism ; Rats ; Ribosomal Protein S6 Kinases, 70-kDa/*metabolism ; Signal Transduction/drug effects ; Thiazolidinediones/*pharmacology