Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts.

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies

Prognostic Factors and Clinical Outcomes of High-Dose Chemotherapy followed by Autologous Stem Cell Transplantation in Patients with Peripheral T Cell Lymphoma, Unspecified: Complete Remission at Transplantation and the Prognostic Index of Peripheral T Cell Lymphoma Are the Major Factors Predictive of Outcome

AbstractHigh-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) offers a rescue option for T cell lymphoma patients with poor prognosis. However, the effectiveness of HDT/ASCT in patients with various peripheral T cell subtypes, optimal transplant timing, and the prognostic factors that predict better outcomes, have not been identified. We retrospectively investigated the clinical outcomes and prognostic factors for HDT/ASCT in 64 Korean patients with peripheral T cell lymphoma, unspecified (PTCL-U) between March 1995 and February 2007. The median age at transplantation was 44 years (range: 15-63 years). According to the age-adjusted International Prognostic Index (a-IPI) and the prognostic index of PTCL (PIT), 8 patients (12.5%) were in the high-risk group and 16 (26.6%) had the 2-3 PIT factors, respectively. After a median follow-up of 29.7 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 53.0% ± 7.5% and 44.3% ± 7.0%, respectively. Univariate analysis showed that poor performance status, high lactate dehydrogenase (LDH) levels, high a-IPI score, high PIT classes, failure to achieve complete response (CR) at transplantation, and nonfrontline transplantation were associated with poor OS. Multivariate analysis showed that failure to achieve CR at transplantation (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.78-7.93) and 2-3 PIT factors (HR 3.76; 95% CI 1.02-5.42) were independent prognostic factors for OS. Failure to achieve CR at transplantation and high PIT are negative predictable factors for survival following HDT/ASCT in patients with PTCL-U

The Effect of Direct Communication between Emergency Physicians and Interventional Cardiologists on Door to Balloon Times in STEMI

We developed an institutional protocol mandating emergency physicians to contact the interventional cardiologist directly in all cases of ST-segment elevation myocardial infarction (STEMI) and hypothesized that this would reduce door-to-balloon-times (DTBT). From January 2004 to July 2006, 208 patients with STEMI were treated with primary percutaneous coronary intervention (PCI). A total of 144 patients were treated before implementing the new protocol ("before") and 64 patients were treated after the implementation ("after"). The DTBT was significantly reduced from 148±101 min to 108±56 min (p<0.05). While only 25% of the "before" patients received PCI within 90 min after arrival, 50% of the "after" patients received PCI within 90 min (p<0.05). There were no significant differences between two groups in other outcomes (postprocedural TIMI flow, mortality, subsequent stroke, heart failure, shock, reinfarction, length of stay in intensive care unit, and the total hospital length of stay). In conclusion, mandating emergency physicians to directly notify interventional cardiologists of all STEMI patients reduces DTBT

Upregulation of Glutamate Receptors in Rat Cerebral Cortex with Neuronal Migration Disorders

Neuronal migration disorders (NMDs) constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes on radiation-induced NMD in rats. The lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic and immunohistochemical findings for glutamate receptor subunit proteins on NMD cortex were correlated with development of behavioral seizures and EEG abnormality. Spontaneous seizures uncommonly occurred in NMD rats (5%); however, clinical stages of seizures were significantly increased in NMD rats by an administration of kainic acid. Brains taken from irradiated rats revealed gross and histopathologic features of NMD. Focal cortical dysplasia was identified by histopathology and immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1 and NR2A/B immunoreactivities were demonstrated in cytomegalic and heterotopic neurons of NMD rats. The results of the present study indicate that epileptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs

Efficacy and Tolerability of Peginterferon Alpha Plus Ribavirin in the Routine Daily Treatment of Chronic Hepatitis C Patients in Korea: A Multi-Center, Retrospective Observational Study

Background/Aims: We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea. Methods: We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea. Results: Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was &gt;= 6x10(5) IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p&lt;0.001), genotype 2/3 (p&lt;0.001), HCV RNA &lt;6x10(5) IU/mL (p=0.005) and adherence to the drug &gt;80% of the planned dose (p&lt;0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%). Conclusions: Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.This study was supported by the Korean Association for the Study of the Liver in 2009

Ectopic over-expression of tristetraprolin in human cancer cells promotes biogenesis of let-7 by down-regulation of Lin28

Tristetraprolin (TTP) is a AU-rich element (ARE) binding protein and exhibits suppressive effects on cell growth through down-regulation of ARE-containing oncogenes. The let-7 microRNA has emerged as a significant factor in tumor suppression. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. In this work, an unexpected link between TTP and let-7 has been found in human cancer cells. TTP promotes an increase in expression of mature let-7, which leads to the inhibition of let-7 target gene CDC34 expression and suppresses cell growth. This event is associated with TTP-mediated inhibition of Lin28, which has emerged as a negative modulator of let-7. Lin28 mRNA contains ARE within its 3′-UTR and TTP enhances the decay of Lin28 mRNA through binding to its 3′-UTR. This suggests that the TTP-mediated down-regulation of Lin28 plays a key role in let-7 miRNA biogenesis in cancer cells

Effect of geometrical parameters in micro-grooved crosshatch pattern under lubricated sliding friction

Tribological test was carried out using a pin-on-disc geometry with textured SKD11 pin on bearing steel disc, under sliding in paraffin oil. Micro-grooved crosshatch pattern has been fabricated with various angles and widths. The effects of geometrical parameters on friction were mainly examined in mixed and elastohydrodynamic lubrication. The results show that friction control can be achieved by fabricating the micro-grooved crosshatch pattern on a contact surface. It is observed that each geometrical parameter of texture influence on friction, especially decrease of groove aspect ratio and increases of groove sliding length show friction reduction performance. Crucial parameter Gl was proposed for micro-grooved crosshatch texture. The friction mechanism is explained by micro fluid flow with limited theoretical approach

A Study to Suggest Monthly Baseflow Estimation Approach for the Long-Term Hydrologic Impact Analysis Models: A Case Study in South Korea

Changes in both land use and rainfall patterns can lead to changes in the hydrologic behavior of the watershed. The long-term hydrologic impact analysis (L-THIA) model has been used to predict such changes and analyze the changes in mitigation scenarios. The model is simple as only a small amount of input data are required, but it can predict only the direct runoff and cannot determine the streamflow. This study, therefore, aimed to propose a method for predicting the monthly baseflow while maintaining the simplicity of the model. The monthly baseflows for 20 watersheds in South Korea were estimated under different land use conditions. Calibration of the monthly baseflow prediction method produced values for R2 and the Nash–Sutcliffe efficiency (NSE) within the ranges of 0.600–0.817 and 0.504–0.677, respectively; during validation, these values were in the ranges of 0.618–0.786 and 0.567–0.727, respectively. This indicates that the proposed method can reliably predict the monthly baseflow while maintaining the simplicity of the L-THIA model. The proposed model is expected to be applicable to all the various forms of the model