The effect of radiotherapy dose on survival in stage III non-small-cell lung cancer patients undergoing definitive chemoradiotherapy.

Background: In this study, we examined trends in the radiotherapy dose prescribed and the effect of dose escalation on survival in patients with stage III lung cancer.

Materials And Methods: Radiation dose prescription patterns were analyzed for 38,848 patients in the National Cancer Database with clinical stage III disease who underwent concurrent chemoradiation between 2004 and 2011 to a dose between 57 and 80 Gy. Survival information was available for patients diagnosed from 2004 to 2006 (n = 12,024).

RBx10080307, a dual EGFR/IGF-1R inhibitor for anticancer therapy.

Pharmacological intervention of epidermal growth factor receptor (EGFR) family members by antibodies or small molecule inhibitors has been one of the most successful approaches for anticancer therapy. However this therapy has its own limitations due to the development of resistance, over a period of time. One of the possible causes of the development of resistance to the therapy with EGFR inhibitors could be the simultaneous activation of parallel pathways.

Improved survival associated with neoadjuvant chemoradiation in patients with clinical stage IIIA(N2) non-small-cell lung cancer.

Introduction: Optimal management of clinical stage IIIA-N2 non-small-cell lung cancer (NSCLC) is controversial. This study examines whether neoadjuvant chemoradiation plus surgery improves survival rates when compared with other recommended treatment strategies.

Methods: Adult patients from the National Cancer Database, with clinical stage IIIA-N2 disease definitively treated between 1998 and 2004 at American College of Surgeons Commission on Cancer accredited facilities, were included in the study.

Comparative deacetylase activity of wild type and mutants of SIRT1.

SIRT1, human ortholog of yeast SIR2 protein, deacetylates histones and several other transcription factors. Recently, SIRT1 has emerged as a drug target for treating age related diseases, type II diabetes, neurodegeneration, inflammation and cancer. Here, we have optimized production of functionally active wild type full-length SIRT1 protein and its N-terminal deleted mutants.

Purification of recombinant human phosphodiesterase 7A expressed in Dictyostelium discoideum.

Phosphodiesterase plays an important role in regulating inflammatory pathways and T cell function. The development of phosphodiesterase 7 inhibitor may give better efficacy profile over phosphodiesterase 4 inhibitors. However, the recombinant phosphodiesterase 7 is required in large quantity for high-throughput screening of new drugs by in vitro enzymatic assays.

Differential gene expression analysis of a known hepatotoxin, N-acetyl-p-amino-phenol (APAP) as compared to its non-toxic analog, N-acetyl-m-amino-phenol (AMAP) in mouse liver.

Drug-induced hepatotoxicity is one of the most common adverse events associated with drug withdrawal from the market. Elucidating the molecular mechanism of hepatotoxicity is essential to predict the safety of a new molecule. To examine genes involved in hepatotoxicity, we have used oligonucleotide CodeLink Bioarrays and determined the transcriptional profile of mice liver treated with hepatotoxic drug N-acetyl-p-amino-phenol (APAP) as well as its non-toxic analog N-acetyl-m-amino-phenol (AMAP).

Cloning, stable expression of human phosphodiesterase 7A and development of an assay for screening of PDE7 selective inhibitors.

Phosphodiesterases (PDEs) constitute a superfamily of enzymes that plays an important role in signal transduction by catalysing the hydrolysis of cAMP and cGMP. cDNA encoding PDE7A1 subtype was cloned and a stable recombinant HEK 293 cell line expressing high levels of PDE7A1 was generated. Transient transfection of pCRE-Luc plasmid, harboring luciferase reporter gene into the stable recombinant cell line and subsequent treatment with PDE7 inhibitor, resulted in a dose-dependent increase in luciferase activity.

Development of a cell-based assay for screening of phosphodiesterase 10A (PDE10A) inhibitors using a stable recombinant HEK-293 cell line expressing high levels of PDE10A.

The cDNA encoding PDE10A (phosphodiesterase 10A) was cloned and a stable recombinant HEK-293 (human embryonic kidney-293) cell line expressing high levels of PDE10A was generated. Transient transfection of pCRE-Luc plasmid, harbouring the luciferase reporter gene under the control of CRE (cAMP-response element)-binding sequence, into the stable recombinant cell line, followed by treatment with PDE10 inhibitor, resulted in a dose-dependent increase in luciferase activity. This method provides a simple and sensitive cell-based assay for screening of PDE10 inhibitors for development of novel therapeutics for the treatment of neurological disorders.

A reporter gene assay for screening of PDE4 subtype selective inhibitors.

Phosphodiesterase (PDE) constitutes a superfamily of enzymes that catalyze the hydrolysis of cAMP and cGMP into their corresponding monophosphates and play an important role in diverse physiological functions. The present study provides a process for identifying PDE4 subtypes selective inhibitors using a reporter gene assay. Stable recombinant HEK-293 cell lines expressing high levels of PDE4A4B, PDE4B2A, and PDE4D3 subtypes individually were generated.

Assessment of Aegilops tauschii for resistance to biotypes of wheat curl mite (Acari: Eriophyidae).

Aegilops tauschii, the wild diploid D-genome progenitor of wheat, Triticum aestivum L., is an important source of resistance to several arthropod pests and pathogens. A total of 108 Ae.