Erlotinib as salvage treatment after failure to first-line Gefitinib in non-small cell lung cancer

Purpose Chemotherapy is the mainstay treatment for advanced non-small cell lung cancer (NSCLC). Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recently shown to be effective as a first-line treatment in Asian patients with advanced NSCLC, especially for those with favourable clinical features such as female, non-smoker and adenocarcinoma. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment. The purpose of this study is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib. Method Retrospective review of NSCLC patients with favourable clinical features who received gefitinib as firstline treatment and subsequent salvage treatment with erlotinib. Results A total of 21 patients with NSCLC were included in the study. Among them, 18 (85.7%) patients had disease control with gefitinib and 12 (57.1%) patients with salvage erlotinib. There was an association between the disease control with gefitinib and erlotinib (p = 0.031). The disease control rate of erlotinib was independent of the chemotherapy use between the two EGFR-TKIs. Conclusion For NSCLC patients with favourable clinical features, erlotinib was effective in those who had prior disease control with first-line gefitinib. © Springer-Verlag 2009.published_or_final_versionSpringer Open Choice, 01 Dec 201

High Energy Cosmic Rays From Supernovae

Cosmic rays are charged relativistic particles that reach the Earth with extremely high energies, providing striking evidence of the existence of effective accelerators in the Universe. Below an energy around $\sim 10^{17}$ eV cosmic rays are believed to be produced in the Milky Way while above that energy their origin is probably extragalactic. In the early '30s supernovae were already identified as possible sources for the Galactic component of cosmic rays. After the '70s this idea has gained more and more credibility thanks to the the development of the diffusive shock acceleration theory, which provides a robust theoretical framework for particle energization in astrophysical environments. Afterwards, mostly in recent years, much observational evidence has been gathered in support of this framework, converting a speculative idea in a real paradigm. In this Chapter the basic pillars of this paradigm will be illustrated. This includes the acceleration mechanism, the non linear effects produced by accelerated particles onto the shock dynamics needed to reach the highest energies, the escape process from the sources and the transportation of cosmic rays through the Galaxy. The theoretical picture will be corroborated by discussing several observations which support the idea that supernova remnants are effective cosmic ray factories.Comment: Final draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdi

Schlieren Studies of Compressibility Effects on Dynamic Stall of Airfoils in Transient Pitching Motion

Compressibility effects on the flowfield of an airfoil executing rapid transient pitching motion from 0 - 60 degrees over a wide range of Mach numbers and pitching rates were studied using a stroboscopic schlieren flow visualization technique. The studies have led to the first direct experiments] documentation of multiple shocks on the airfoil upper surface flow for certain conditions. Also, at low Mach numbers, additional coherent vortical structures were found to be present along with the dynamic stall vortex, whereas at higher Mach numbers, the flow was dominated by a single vortex. The delineating Mach number for significant compressibility effects was 0.3 and the dynamic stall process was accelerated by increasing the Mach number above that value. Increasing the pitch rate monotonically delayed stall to angles of attack as large as 27 degrees.AFOSR-MIPR-87-0029 and 88-0010NAVAIRAR

Cyclic-di-AMP synthesis by the diadenylate cyclase CdaA is modulated by the peptidoglycan biosynthesis enzyme GlmM in lactococcus lactis

© 2016 John Wiley & Sons Ltd. The second messenger cyclic-di-adenosine monophosphate (c-di-AMP) plays important roles in growth, virulence, cell wall homeostasis, potassium transport and affects resistance to antibiotics, heat and osmotic stress. Most Firmicutes contain only one c-di-AMP synthesizing diadenylate cyclase (CdaA); however, little is known about signals and effectors controlling CdaA activity and c-di-AMP levels. In this study, a genetic screen was employed to identify components which affect the c-di-AMP level in Lactococcus. We characterized suppressor mutations that restored osmoresistance to spontaneous c-di-AMP phosphodiesterase gdpP mutants, which contain high c-di-AMP levels. Loss-of-function and gain-of-function mutations were identified in the cdaA and gdpP genes, respectively, which led to lower c-di-AMP levels. A mutation was also identified in the phosphoglucosamine mutase gene glmM, which is commonly located within the cdaA operon in bacteria. The glmM I154F mutation resulted in a lowering of the c-di-AMP level and a reduction in the key peptidoglycan precursor UDP-N-acetylglucosamine in L. lactis. C-di-AMP synthesis by CdaA was shown to be inhibited by GlmMI154F more than GlmM and GlmMI154F was found to bind more strongly to CdaA than GlmM. These findings identify GlmM as a c-di-AMP level modulating protein and provide a direct connection between c-di-AMP synthesis and peptidoglycan biosynthesis. c-di-AMP is an essential signalling molecule which affects peptidoglycan homeostasis and resistance against various stressors, however little is known regarding how the c-di-AMP level is regulated in the cell. Here we identify the peptidoglycan biosynthesis enzyme GlmM as a modulator of c-di-AMP synthesis through its regulation of diadenylate cyclase enzyme CdaA activity in Lactococcus lactis

Integrated human papillomavirus analysis as an adjunct for triage of atypical cervical cytology

published_or_final_versio

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Association between Self-esteem and Smoking among Religious Schools Students in Petaling District, Selangor

Introduction : According to the Youth Behaviour Risk Factor Surveillance (YBRFSS, 2011) in Malaysia, the prevalence of smokers nationally among Form 1, 2 and 4 students government secondary school students was 9.1% (ever smokers) and 8.7% (current smokers). However, there is limited information on the prevalence of smoking among religious secondary school students and self-esteem as risk factor. Thus, this study was conducted to determine the prevalence and factors associated with smoking among the religious secondary school students in Petaling district, Selangor. Methods: A cross-sectional study was conducted among 899 students. The schools were selected using cluster sampling and self-administered questionnaire was used. Data was analyzed using chi-square test and multivariate logistic regression to identify the independent factors for smoking. Results: The response rate was 94%. The prevalence of ever smoking was 10.1%; 3.9% among female and 18.6% among male. The median age (interquartile range) of smoking initiation was 12.00 (4.01) years. The results showed that independent factors for smoking were: males (OR= 5.47); age group 14-15years (OR=2.82) and 16-17 years (OR=3.63) and having low self -esteem (OR=6.24). Conclusion: prevalence of ever smokers is higher when compared to YBRFSS, (2011) and it was revealed that most of the smokers started smoking even before secondary school. The results also revealed the importance of promoting self-esteem. Efforts in smoking prevention should therefore be focused on curbing the initiation of the acts and improving students’ self-worth

NEMO: A Project for a km3^3 Underwater Detector for Astrophysical Neutrinos in the Mediterranean Sea

The status of the project is described: the activity on long term characterization of water optical and oceanographic parameters at the Capo Passero site candidate for the Mediterranean km$^3$ neutrino telescope; the feasibility study; the physics performances and underwater technology for the km$^3$; the activity on NEMO Phase 1, a technological demonstrator that has been deployed at 2000 m depth 25 km offshore Catania; the realization of an underwater infrastructure at 3500 m depth at the candidate site (NEMO Phase 2).Comment: Proceeding of ISCRA 2006, Erice 20-27 June 200

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Hsp21potentiates antifungal drug tolerance in Candida albicans

Peer reviewedPublisher PD