Co-Overexpression of Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Adversely Affects the Postoperative Survival in Non-small Cell Lung Cancer

IntroductionCyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 have been found to be overexpressed in non-small cell lung cancer (NSCLC). The aim of this study was to investigate the expression profiles of COX-2 and mPGES-1 and their correlation with the clinical characteristics and survival outcomes in patients with resected NSCLC.Methods/ResultsSeventy-nine paired adjacent normal-tumor matched samples were prospectively procured from patients undergoing surgery for NSCLC. The protein levels of COX-2 and mPGES-1 were assessed by Western blot analysis. Overexpression in the tumor sample was defined as more than twofold increase in protein expression compared with the corresponding adjacent normal tissue. Co-overexpression of COX-2 and mPGES-1 were further confirmed by immunohistochemistry. COX-2 was overexpressed in 58% and mPGES-1 in 70% of the tumor samples (p < 0.0001). Co-overexpression of mPGES-1 and COX-2 was noted in 43%, and they were unrelated to each other (p = 0.232). Co-overexpression of both proteins was significantly associated with less tumor differentiation (p = 0.046), tumor size larger than 5 cm (p = 0.038), and worse survival status during the follow-up (p = 0.036). Multivariate analysis showed that in addition to overall stage, co-overexpression of both proteins adversely affected the overall (hazard ratio, 2.40; p = 0.045) and disease-free survivals (hazard ratio, 2.27; p = 0.029).ConclusionsOverexpression of either COX-2 or mPGES-1 is common but unrelated in NSCLC. Co-overexpression of both COX-2 and mPGES-1 adversely affects postoperative overall and disease-free survivals

Protective Effect of Caffeic Acid on Paclitaxel Induced Anti-Proliferation and Apoptosis of Lung Cancer Cells Involves NF-κB Pathway

Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC50 dose of paclitaxel (PTX), an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

Mortality, readmission, and reoperation after hip fracture in nonagenarians

Abstract Background Osteoporotic hip fractures are associated with high mortality and morbidity in people of advanced age; however, few studies have investigated the complication rates in nonagenarians. In this study, we applied a competing risk analysis to estimate the mortality, readmission, and reoperation rates after surgery for hip fracture among nonagenarians. Methods A total of 11,184 nonagenarians (aged ≥ 90) who received surgery for hip fracture during the period 1 January 1997 and 31 December 2010 were selected from Taiwan’s National Health Insurance (NHI) database. Nonagenarians were followed up until the end of 2012, death, or the date they left the NHI program. Cumulative mortality was estimated using the Kaplan-Meier analysis and risk factors for mortality were investigated using a Cox proportional hazards model. Competing risk analysis was used to estimate cumulative incidence rates and to assess the risk factors for reoperation and readmission. Results The mortality rates were 29.5% at 1 year, 45.0% at 2 years and 78.1% at 5 years. The cumulative incidence rates of reoperation were 7.3% at 1 year, 9.2% at 2 years and 11.6% at 5 years whereas those of readmission were 18.9% at 1 month and 24.1% at 3 months. Significant risk factors for death included age, male gender, trochanteric fracture, and higher Charlson comorbidity index (CCI) whereas those for reoperation were age, cervical fracture and higher CCI. Furthermore, age, male gender, and higher CCI were risk factors for readmission. Conclusions The overall 2-years mortality rate among nonagenarians in Taiwan was around 45%, the 2-years reoperation rate was around 9% and the 90-days medical complication rate was around 24%. High complication rates are associated with increased risk for death. Postoperative care to prevent medical complications is likely the most effective strategy to reduce mortality rates among nonagenarians with hip fracture

Empirical Evidences for the Endogenous Growth Generated by Evolution in Division of Labor

Following up the empirical works of Jones (1995a,b) that reject two classes of the major endogenous growth models: the AK models and R&D based models, the paper tests the third class of endogenous growth models that generate endogenous evolution in division of labor against empirical data. It is shown that this class of endogenous growth models not only avoid scale effect, but also accommodate both convergence and divergence phenomena. One of the hypotheses generated by this class of endogenous growth models is that the divergence phenomenon takes place first between each pair of economies that enter the take off stage at different points in time, then the convergence phenomenon follows. This implies that the difference in per capita real income between the two economies is an inverse U shape curve. The empirical data strongly support the hypothesis

Empirical Evidences for the Endogenous Growth Generated by Evolution in Division of Labor

Following up the empirical works of Jones (1995a,b) that reject two classes of the major endogenous growth models: the AK models and R&D based models, the paper tests the third class of endogenous growth models that generate endogenous evolution in division of labor against empirical data. It is shown that this class of endogenous growth models not only avoid scale effect, but also accommodate both convergence and divergence phenomena. One of the hypotheses generated by this class of endogenous growth models is that the divergence phenomenon takes place first between each pair of economies that enter the take off stage at different points in time, then the convergence phenomenon follows. This implies that the difference in per capita real income between the two economies is an inverse U shape curve. The empirical data strongly support the hypothesis

Comparison of a minimally invasive technique with open tension band wiring for displaced transverse patellar fractures

Background: Open reduction and internal fixation with tension band wire is the standard treatment for displaced transverse patellar fractures. Recently, some minimally invasive techniques have been proposed as possible alternative methods. This retrospective study compared a newly reported percutaneous osteosynthesis with conventional open method for the treatment of displaced transverse patellar fractures. Methods: The minimally invasive technique was performed by percutaneous osteosynthesis with modified Carpenter’s (POMC) technique, using figure-eight wiring through two-paired cannulated screws under the control of arthroscopy and fluoroscopy. The conventional open surgery was performed with open modified anterior tension band (OMATB) technique. Totally 60 displaced transverse fractures were included in our study. Twenty were treated with percutaneous technique and 40 with open method. Outcome assessment included analysis of radiographic images, range of motion, Lysholm scores, complications, and reoperations. Results: Mean follow-up was 37.3 months. Comparison of POMC and OMATB groups showed statistically significant results as follows: shorter surgical time, 70.4 ± 12.5 minutes for POMC group; greater degrees of flexion, 140.4 ± 6.1 for POMC group; better total range of motion, 139.6 ± 8.2 for POMC group; higher Lysholm scores, 93.6 ± 3.1 for POMC group. Frequencies of total complications and reoperations were significantly lower in POMC group. Conclusion: POMC method was a reproducibly reliable method, offering better functional outcome, lower incidence of complications, and reoperations, as compared with standard OMATB group for transverse patellar fractures. Nevertheless, it is not recommended for severely comminuted fractures