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Phloretin is one of the apple polyphenols with anticancer activities. Since tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves important roles in inducing apoptosis, the present study examined the effect of phloretin on TRAIL-induced apoptosis in colon cancer cells. Treatment with both phloretin and TRAIL markedly suppressed the survival of cancer cells from several colon cancer cell lines compared with that of cells treated with either TRAIL or phloretin. Additionally, decreased numbers of colonies were observed following addition of phloretin and TRAIL. Furthermore, TRAIL- and phloretin-treated HT-29-Luc cells exhibited decreased luciferase activity. Increased apoptosis was observed in phloretin- and TRAIL-treated HT-29-Luc colon cancer cells, accompanying elevated levels of cleaved poly(ADP-ribose) polymerase, and caspase-3, -8 and -9. The expression levels of MCL1 apoptosis regulator BCL2 family member (Mcl-1) were decreased following addition of phloretin in colon cancer cells. In addition, overexpression of Mcl-1 in phloretin- and TRAIL-treated HT-29-Luc cells resulted in increased cell survival. Treatment of HT-29-Luc cells with a combination of cycloheximide (CHX) and phloretin led to a more prominent decrease in Mcl-1 expression compared with that in cells treated with CHX alone, while Mcl-1 expression was recovered by treatment with MG132. Binding of ubiquitin with Mcl-1 was verified using immunoprecipitation. Intraperitoneal injection of both TRAIL and phloretin into tumor xenografts was associated with a decreased tumor volume compared with that following injection with either TRAIL or phloretin. Overall, the present results suggest a synergistic effect of phloretin on TRAIL-induced apoptosis in colon cancer cells.

Background/Aims: Patients with pancreatic cancer (PC) generally have poor clin ical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indi cators in patients with advanced PC treated with gemcitabine-based chemothera py as the first line regimen. Methods: This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. Results: Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was signif icant (p < 0.001) among three groups divided by the number of marker-related risks. Conclusions: Baseline inflammatory markers including NLR, PLR, and CRP-al bumin ratio are useful in predicting survival rates in patients with PC. Combin ing these three markers is proven to be valuable.

To evaluate the efficacy of intraoperative extrinsic manual bladder compression (Crede maneuver) for trans-obturator tape adjustment during mid-urethral sling surgery in women with stress urinary incontinence and those with mixed urinary incontinence. The study included 148 randomly selected women who underwent mid-urethral sling surgery with trans-obturator tape for stress urinary incontinence between January 2016 and May 2017. Subgroup analysis of 66 women with mixed urinary incontinence included 43 patients from the Crede maneuver group and 23 from the non-Crede maneuver group. In the Crede maneuver group, the pattern of urine leakage was determined during the Crede maneuver, and tape tension was adjusted according to the pattern. The cure rate was 86.6% and improved rate was 11.9% in the Crede maneuver patients. The cure rate was 50.6% and improved rate was 38.3% in the non-Crede maneuver patients. The success rate was significantly higher in the Crede than in the non-Crede maneuver group (p = 0.023). In subgroup analysis of patients with mixed urinary incontinence, the cure rate was 81.4% and improved rate was 16.3% in the Crede maneuver group. The cure rate was 43.5% and improved rate was 47.8% in the non-Crede maneuver group. The cure rate was significantly higher in the Crede maneuver group (p = 0.007). Intraoperative trans-obturator tape adjustment using the Crede maneuver to identify the leaking pattern significantly improved the success rate in women with mixed urinary incontinence, and Crede maneuver-directed adjustment significantly improved the cure rate.

Management of endometrial cancer, an adenocarcinoma of the endometrium which occupies most uterine corpus neoplasms, including uterine sarcomas, has been more relevant due to its increasing incidence. Extensive research on tumorigenesis molecular mechanisms and molecular characterization across cancers has brought paradigm shifts in the treatment of various malignant tumors. Endometrial cancer treatment has been traditionally guided according to the disease extent or histology types, while recent studies on molecular features have led to the introduction of targeted agents into clinical use, along with conventional chemotherapeutic agents in patients with recurrent or metastatic disease. Considering the proven efficacy and relatively tolerable toxicities of targeted therapies across malignant tumors, improvement of treatment outcomes is also expected in endometrial cancer by adopting an individualized therapy depending on the specific molecular features. Efficacy assessment of new biological agents is still ongoing based on previous preclinical data on endometrial cancer molecular features. Here, endometrial cancer molecular characterization will be reviewed, and then, we will introduce preclinical data, directing the adoption of new biological agents.

Amplification of fibroblast growth factor receptor2 (FGFR2) has been regarded as a druggable target in gastric cancer (GC). Despite known potential of AZD4547, a selective inhibitor of FGFR 1-3, to suppress tumorigenic effects of activated FGFR2, resistance to the targeted agent has been an unresolved issue. This study was performed to elucidate the mechanism of AZD4547 resistance in GC cells. SNU-16 cells were used to establish an AZD4547-resistant GC cell line, SNU-16R. Elevated phosphorylation of EphB3 was confirmed using the Human Phospho-Receptor Tyrosine Kinase Array kit. A tyrosine kinase inhibitor (TKI) of EphB3 was used to investigate the effects of suppressed EphB3 activity in the SNU-16R cell line. SNU-16R cells exhibited upregulated phosphorylation of EphB3. Treatment of SNU-16R cells with the EphB3 TKI resulted in induction of apoptosis, decreased cellular viability, and cell cycle arrest at sub-G1 phase. SNU-16R cells expressed upregulated levels of N-cadherin, vimentin, Snail, matrix metalloproteinase 2 (MMP-2), and MMP-9, and reduced levels of E-cadherin, characteristic of epithelial to mesenchymal transition (EMT). Matrigel invasion assay also demonstrated the increased invasiveness of SNU-16R cells. EphB3 TKI treatment inhibited EMT of SNU-16R cells. Activation of mammalian target of rapamycin (mTOR) through the Ras-ERK1/2 pathway was suggested as the signal transduction mechanism downstream EphB3 by showing enhanced phosphorylation of Raf-1, MEK1/2, ERK1/2, mTOR and its downstream substrates in SNU-16R cells. As expected, EphB3 TKI decreased phosphorylation of these proteins. Our data suggest phosphorylation of mTOR through signaling by EphB3 is a potential mechanism of AZD4547 resistance in GC cells.

Hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) play important roles in cancer progression in various cancer cell lines. Although genipin, a constituent of Gardenia fruit, has been shown to have anti-tumor activity, its role in the suppression of HIF-1 and its downstream target genes is not well understood. We examined the effect of genipin on the intracellular level of HIF-1α and extracellular level of VEGF using the colon cancer cell line HCT116. We observed that genipin suppressed the accumulation of HIF-1α under hypoxia in various cancer cell lines, including HCT116, via the modulation of protein degradation. Genipin also suppressed the expression of VEGF and the invasion of colon cancer cells by blocking the extracellular signal-regulated kinase signaling pathway. Taken together, our results provide new insights into the potential role of genipin in suppressing colon cancer progression.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT+RT; RT+CT) and concurrent modalities (CCRT; CCRT+CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P=0.027), prognostic index for NK/T-cell lymphoma (PINK) (P=0.026) and types of initial treatment (P=0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P=0.021) and PINK-EBV DNA (PINK-E) (P=0.002) significantly impacted on PFS; whereas ECOG performance score (P=0.008) and stage (P

AIM To evaluate the prognostic role of interim analysis of 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) volumetric parameters in patients with recurrent or metastatic advanced gastric cancer (AGC) treated with fluoropyrimidine-based palliative chemotherapy. METHODS Forty-four patients who underwent baseline and interim PET/CT scanning during palliative chemotherapy were analyzed retrospectively. Initial and change of metabolic parameters (MP) - metabolic tumor volume (MTV), tumor lesion glycolysis (TLG) and maximum and mean standardized uptake values (SUV) were measured with PET/CT. Metabolic change was measured by ∆MP (%) = (MPinterim - MPinitial )/MP initial × 100. Independent t-test was employed to compare values of initial, interim and change of metabolic parameters between each response group. Log-rank test was employed for univariate analysis, and multivariate analysis was performed using the Cox proportional hazards regression model to determine independently significant prognostic factors. RESULTS Reduced percentage values of maximum and mean SUV on interim PET/CT and initial values of volumetric parameters (MTV and TLG) were significant predicting factors to response to fluoropyrimidine-based palliative chemotherapy. The decreased percentage values of metabolic parameters as well as maximum and mean SUV with receiver operating characteristic (ROC) curve determined cut-off points were significant prognostic factors for overall survival and progression-free survival in univariate and multivariate analyses. CONCLUSION Measurement of metabolic decrease of volumetric parameters by interim PET/CT analysis is useful to determine the prognosis of patients with recurrent or metastatic AGC.

Genipin, a major component of Gardenia jasminoides Ellis fruit, has been shown to inhibit the growth of gastric, prostate, and breast cancers. However, the anti-proliferative activity of genipin in colorectal cancer (CRC) has not been characterized. Herein, we demonstrated that genipin inhibits the proliferation of CRC cells and that genipin suppressed the Hedgehog pathway. Further investigation showed that p53 and NOXA protein levels were increased during inhibition of Hedgehog pathway-mediated apoptosis in CRC cells. We also showed that p53 modulated the expression of NOXA during genipin-induced apoptosis, and suppression via SMO also played a role in this process. Subsequently, GLI1 was ubiquitinated by the E3 ligase PCAF. In a xenograft tumor model, genipin suppressed tumor growth, which was also associated with Hedgehog inactivation. Taken together, these results suggest that genipin induces apoptosis through the Hedgehog signaling pathway by suppressing p53. These findings reveal a novel regulatory mechanism involving Hedgehog/p53/NOXA signaling in the modulation of CRC cell apoptosis and tumor-forming defects.

Salinity is one of the major abiotic stresses that severely effects rice production throughout the world. Previously, there have not been many studies which focused on studying diversity among rice germplasm based on specific physiological traits for salt tolerance. Our diversity study was based on physiological traits such as Na+ concentration, K+ concentration, K+/Na+ ratio, osmotic potential, and biomass which are major components determining salt tolerance. This study has systematically analyzed phenotypic data of 191 germplasms in two different salt concentrations apart from the control. The current study identified salt tolerant germplasms based on their response to a single physiological trait as well as a combination of different physiological traits. Some of the germplasm identified outperformed known salt tolerant cultivar Pokkali. This study identifies correlation among various physiological traits. The salt tolerant germplasms can be taken forward into developing better varieties by conventional breeding and exploring genes for salt tolerance.

Background The present study aimed to evaluate the indications for a second prostate biopsy in patients suspected with prostate cancer after an initial negative prostate biopsy. Methods The present study included 421 patients who underwent repeat prostate biopsy between January 2007 and December 2015 at three hospitals. Clinicopathological data, including patient age, body mass index, history of prostate biopsy, prostate volume, prostate-specific antigen (PSA) level, PSA density, PSA velocity, and PSA fluctuation patterns, were analyzed. The patients were stratified into two groups based on the first PSA pattern (increase/decrease) within 1 year after the initial negative prostate biopsy. Results Prostate cancer was detected in 100 (23.8%) of the 421 patients at the second prostate biopsy. In patients with a PSA decrease at the first follow-up, prostate volume and number of increases in the PSA level from the initial prostate biopsy were predictors for prostate cancer diagnosis at the second prostate biopsy. In patients with a steady PSA increase after the initial prostate biopsy, prostate volume and number of biopsy cores were predictors for prostate cancer diagnosis at the second prostate biopsy. Conclusion The indications for a second prostate biopsy are a low prostate volume and a high number of increases in the PSA level among patients with a PSA decrease at the first follow-up and a low prostate volume and a high number of biopsy cores among patients with a PSA increase at the first follow-up.

Background: The impacts of pulmonary function in patients with metastatic non-small cell lung cancer (NSCLC) and extended disease stage small cell lung cancer (SCLC-ED) treated with palliative chemotherapy remain to still be determined. Methods: Results of spirometry performed in 449 patients with either stage IV NSCLC (n=313) or SCLC-ED (n=136) at diagnosis were reviewed retrospectively. Overall survival (OS) was estimated using the Kaplan-Meier method and compared via a log-rank test. Multivariate analysis was performed using a Cox proportional hazards regression model. Results: The presence of chronic obstructive pulmonary disease (COPD) was not a risk factor for OS in either NSCLC or SCLC. However, NSCLC patients with COPD with a forced expiratory volume in one second (FEV1) value of less than 80% predicted were associated with a worse OS in both univariate and multivariate analyses [hazard ratio (HR): 1.43; 95% confidence interval (CI): 1.04–1.97; P=0.03]. Intriguingly, only the OS of NSCLC patients treated with chemotherapeutic agents was affected by the airflow limitation FEV1 value of less than 80% predicted (P=0.02). Patients with an FEV1 value of less than 80% predicted treated with targeted agents were not associated with OS (P=0.24). On the other hand, NSCLC patients with COPD were significantly linked to the occurrence of pulmonary complications during palliative therapy (P=0.01) but not associated with death resulting from pulmonary complications (P=0.22). Conclusions: Careful attention is required when chemotherapeutic agents are administered to patients with metastatic NSCLC with accompanying COPD with a FEV1 value of less than 80% predicted.

Pudendal nerve block (PNB) is performed for differential diagnosis and treatment of chronic pelvic and perineal pain. Several block methods, such as transvaginal, transperineal, computerized tomography-, ultrasound- and fluoroscopy-guided approach are currently under practice. Compared to others, a fluoroscopy-guided approach has several advantages, such as its relatively low cost, facility and ease of landmark recognition. We depicted a fluoroscopy-guided PNB technique to selectively block and elaborate a pulsed radiofrequency treatment in a 51-year-old man with chronic pelvic and perineal pain. The patient had undergone a ganglion of impar block with a limited pain relief. Thereafter, a PNB was performed and the pain was relieved significantly for 2 weeks. Further PNB with a pulsed radiofrequency treatment reduced the pain for more than 8 weeks. The pain relief sustained up to the time of this report. The fluoroscopy-guided PNB and pulsed radiofrequency treatment allowed simplicity in manipulation and precision in performing the procedures with a favorable outcome.

Intravesical BCG therapy after transurethral resection of bladder tumor (TURB) is considered the most effective treatment for prophylaxis against the recurrence of high risk non-muscle invasive bladder cancer, and generally well tolerated and infectious complication are rare. We reported a case of granulomatous prostatitis is a patient who had undergone intravesical BCG therapy due to non-invasive superficial urothelial carcinoma of bladder. This patient was diagnosed by prostate biopsy because of PSA elevation without any other voiding symptoms and abnormal abscess pocket in transrectal ultrasonography.

Purpose The prognosis of young colorectal cancer (CRC) patients has not fully been addressed. The prognostic significance of systemic inflammatory markers was examined in those patients. Methods A total of 965 patients with resectable CRC were divided into young (≤ 50 years, n = 101) and old groups (> 51 years, n = 864). Neutrophil-to-lymphocyte ratio (NLR) > 5, derived NLR (dNLR) > 3, lymphocyte-to-monocyte ratio (LMR) < 2, platelet-to-lymphocyte ratio (PLR) > 150, and prognostic nutritional index (PNI) < 45 were analyzed for prognosis. Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test. A multivariate analysis was performed using a Cox proportional hazards regression model. Results In the young group, NLR > 5, LMR < 2, and PNI < 45 were significantly associated with OS with univariate analyses. dNLR > 3 and those markers showed significance for PFS. LMR < 2 was a significant marker for poor PFS (hazard ratio [HR], 5.81; P = 0.020) in the multivariate analysis. In the old group, all inflammatory markers were significantly associated with OS and PFS with univariate analyses. LMR < 2 (HR, 2.66; P = 0.016) and PNI < 45 (HR, 2.14; P = 0.016) were independently associated with OS in multivariate analyses. PLR > 150 (HR, 1.45; P = 0.036) and PNI < 45 (HR, 1.73; P = 0.002) were significant markers for PFS. Conclusion Systemic inflammation might be one of biologic factors that influence on prognosis of young CRC.

Biliary tract cancer is a heterogenous group. Gemcitabine plus cisplatin has been the standard chemotherapy for advanced biliary tract cancer, but there is lack of evidence on treatment in patients with intrahepatic cholangiocarcinoma (IHC). We analyzed 29 patients with only IHC who received gemcitabine plus cisplatin between June 2010 and February 2013. The median age was 63 years (range, 40-78 years), and Eastern Cooperative Oncology Group performance status of all patients was

// Seong Hye Park 1, * , Dae-Hee Lee 1, 2, * , Jung Lim Kim 2 , Bo Ram Kim 1 , Yoo Jin Na 1 , Min Jee Jo 1 , Yoon A. Jeong 2 , Suk-Young Lee 2 , Sun Il Lee 3 , Yong Yook Lee 4 , Sang Cheul Oh 1, 2 1 Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul, Republic of Korea 2 Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea 3 Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea 4 The Korean Ginseng Research Institute, Daejeon, Republic of Korea * These authors contributed equally to this work Correspondence to: Sang Cheul Oh, email: sachoh@korea.ac.kr Keywords: metformin, TRAIL, CRC, Mcl-1, Noxa Received: December 20, 2015 Accepted: July 06, 2016 Published: August 09, 2016 ABSTRACT Metformin is an anti-diabetic drug with a promising anti-cancer potential. In this study, we show that subtoxic doses of metformin effectively sensitize human colorectal cancer (CRC) cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which induces apoptosis. Metformin alone did not induce apoptosis, but significantly potentiated TRAIL-induced apoptosis in CRC cells. CRC cells treated with metformin and TRAIL showed activation of the intrinsic and extrinsic pathways of caspase activation. We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL. Further experiments revealed that metformin did not affect mRNA levels, but increased proteasomal degradation and protein stability of Mcl-1. Knockdown of Mule triggered a significant decrease of Mcl-1 polyubiquitination. Metformin caused the dissociation of Noxa from Mcl-1, which allowed the binding of the BH3-containing ubiquitin ligase Mule followed by Mcl-1ubiquitination and degradation. The metformin-induced degradation of Mcl-1 required E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1. Our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through Noxa and favors the interaction between Mcl-1 and Mule, which consequently affects Mcl-1 ubiquitination.

Microporous polyvinylidene difluoride (PVDF) hollow fiber membranes were fabricated via a thermally-induced phase separation (TIPS) method using an environmental-friendly hydrophobic solvent, acetyl tributyl citrate (ATBC, tradename Citroflex ® A4 ). To maximize membrane tensile strength, the TIPS method was fully utilized by spinning fibers with high polymer content. It was observed that the fiber quality was significantly affected by the dope and bore flow rates and compositions, and an appropriate spinning range was established. The prepared membranes were subsequently stretched to tune the porosity, mean pore size, permeability, tensile strength, and fiber strain. A design of experiment (DOE) analysis was conducted using a 3-factor quadratic model to optimize the stretching conditions and to understand the effects of the parameters and interactions thereof. The permeability of the stretched membranes improved by a factor of 35 (15.1–538 L m −2 h −1 bar −1 ), and the tensile strength increased from 7.2 MPa to 8.4 MPa at the expense of the fiber strain. The DOE analysis revealed that the stretching ratio positively affects the permeability and porosity but decreases the fiber strain. On the other hand, it was determined that the stretching temperature positively influences the permeability and fiber strength. The stretched membranes exceeded the PVDF performance upper bound prepared by the TIPS method. The membranes were primarily in the α-phase polymorph, and stretching the fibers up to 40% at 90 °C did not induce any detectable β-phase crystals. The proposed preparation method offers a feasible and sustainable alternative to fabricate hollow fibers membranes with high tensile strength and high permeability.

Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.

Objective: This retrospective study was undertaken to assess the incidence of and risk factors for febrile neutropenia (FN) during adjuvant chemotherapy for early-stage breast cancer (ESBC). Methods: A multicenter survey of three tertiary hospitals was conducted, with data extracted from the records of ESBC patients treated with adjuvant chemotherapy containing AC (doxorubicin, 60 mg/m2 and cyclophosphamide, 600 mg/m2 every 21 days). Assessments included clinical characteristics, chemotherapy dose modifications, and incidence of FN. Results: A total of 610 patients were included for analysis. The incidence of grade 4 neutropenia and FN was 44.6 and 8.5%, respectively. Reduced relative dose intensity (RDI) less than 85% occurred in 11.0% of patients, and there were treatment delays in 12.6% of patients. Multivariate analysis identified several independent predictors for FN, including the presence of grade 4 neutropenia and pretreatment calculated estimated glomerular filtration rate less than 60 ml/min. Conclusion: Patients with ESBC are at substantial risk for FN and reduced RDI when treated with adjuvant AC chemotherapy. Predictive models based on risk factors identified in this study should enable the selective application of supportive measures in an effort to deliver the full dose of chemotherapy.

Background/Objective: The aim of this study was to evaluate the characteristics and prognostic factors of small cell lung cancer (SCLC) with bone metastases. We also investigated the characteristics and predictive factors of skeletal-related events (SREs) in these patients. Materials and Methods: Sixty-one patients who were first diagnosed with SCLC with bone metastases at our institution were included in this retrospective analysis. Results: The overall survival (OS) of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs. 6.17 months, p = 0.015). Poor Eastern Cooperative Oncology Group (ECOG) performance status (PS; ≥2) and higher serum alkaline phosphatase (ALP; above upper normal limit × 2) were independent poor prognostic factors (p = 0.027 for ECOG PS, p = 0.002 for ALP). More than 1 SRE occurred in 21 patients (34.4%). Cervical spine metastasis, thoracic spine metastasis, pelvic bone metastasis, more than 5 bone metastatic regions and higher serum lactate dehydrogenase were correlated with the occurrence of SREs. Thoracic spinal metastasis was a strong predictive factor for the occurrence of SREs (odds ratio = 5.475; 95% CI: 1.080-27.755). Conclusion: Our study demonstrates the poor prognosis of SCLC patients with bone metastases. Physicians should treat SCLC patients with bone metastases with caution.

Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review.

This study investigates the result of thermal stress analysis on burning plate by classes at outdoor gas boiler. In the analysis results at the steady state, the maximum stress and deformations are 666,8MPa at A type and 0.20476mm at B type respectively. The deformation becomes larger as the field goes on from the center to the outside at burning plate. As there are 8 types in the order of maximum stress and deformation, F and C type have safest among 8 types respectively. Therefore, F type becomes most excellent on strength and safety among 8 types. By using the analysis result of burning plate model at gas boiler, it is possible to design the model applied practically at the safe component parameters of boiler system.

Hong Jun Kim,1 Min Jee Jo,2 Bo Ram Kim,2 Jung Lim Kim,2 Yoon A Jeong,2 Yoo Jin Na,2 Seong Hye Park,2 Suk-young Lee,1 Dae-Hee Lee,1,2 Baek-hui Kim,3 Young Do Yoo,4 Sang Cheul Oh1,2 1Division of Oncology and Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea; 2Laboratory of Oncology, Graduate School of Medicine, Korea University, Seoul, Republic of Korea; 3Department of Pathology, College of Medicine, Korea University, Seoul, Republic of Korea; 4Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University, Seoul, Republic of Korea Introduction: Reactive oxygen species modulator-1 (Romo1) is a protein that modulates levels of reactive oxygen species (ROS) and has been reported to affect cancer cell invasion and proliferation via persistent inflammation. Several studies have demonstrated the clinical application of Romo1 as a prognostic marker in non-small cell lung cancer (NSCLC); however, there have been no studies investigating the mechanism by which Romo1 adversely affects the prognosis of these patients. Methods: We examined Romo1, ROS, and vascular endothelial growth factor (VEGF) in tumor tissues immunohistochemically. We conducted survival analyses of patients who had curative resection (n=30) in accordance with clinical parameters including levels of Romo1 expression. Results: Romo1 levels were associated with serologic inflammatory markers and high lymphatic metastatic tendencies. Significantly longer disease-free survival (68.7 vs 24.2 months, P=0.031) and overall survival (92.7 vs 51.6 months) were observed in the group with low Romo1 compared with high Romo1. Survival outcomes were also significantly associated with serologic inflammatory markers. Spearman’s correlation analyses demonstrated significant positive correlations of Romo1 expression with VEGF-C (P=0.008, R=0.478) and ROS (P=0.016, R=0.436) in tumor samples. Conclusion: The current study demonstrates that Romo1 induces lymphatic metastasis of NSCLC by modulating persistent inflammation and oxidative stress (ROS)/VEGF signaling. Lymphatic metastasis associated with elevated Romo1 was shown to be a key reason for unfavorable survival rates. Keywords: non–small cell lung carcinoma, inflammation, reactive oxygen species modulator-1, vascular endothelial growth factor A, reactive oxygen species

Background This study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated. Methods A total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated. Results VTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (

We carried out three-dimensional flow analysis in a clean room. Flow field in a robot experiment system, induced from the moving robot, is numerically studied in this paper. The effects of moving robot in a clean room are investigated in order to find the section of dust accumulation. Contamination on the bottom produced from the moving robot is predicted from the analysis results from the flow fields. Results show that a large swirl flow is formed around the moving robot. Consequently, the optimal flow condition can be obtained by controlling the fluid velocity through the fixing of inlet or outlet position.

This research is that analyze multi-body system that have flexible and rigid body. Transfer robots are widely used mainly in automobile industry owing to its capability to handle heavy parts with high speed in wide range of movement. For the transfer robots to widen the application area, a new three-axis mechanism with heavy payload has been recently developed in consideration of the strength and stiffness. For the purpose, transient dynamic analysis is carried out to find the component position yielding a certain time. Though this research, we can analysis stress distribution and deformation of robot component.

Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres' cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

Gear pump has a simple structure high reliability, easy operation and maintenance, widely used as a source of hydraulic system of hydraulic. In general, the gear pump was designed using variety of variables, the variables through the analysis of the mass flow rate and efficiency. In this paper, three-dimensional flow of the gear pump, in order to produce the optimal design of product, analysis was performed by using commercial software ANSYS v15.0 CFX. And then, combination of design parameters selected by ANSYS was carried out to confirm the simulation result. The efficiency and mass flow rate of the gear pump were studied by varying its rotational speed and the clearance between the gear tip and the housing. In the simulation results, as the rotational speed were increased, the average mass flow rate and efficiency increased. Furthermore, as the clearance between the gear tip and the housing was increased, the average mass flow rate and efficiency decreased.