The Impact of Smoking Status on the Efficacy of Erlotinib in Patients with Advanced Non-small Cell Lung Cancer

Background and objective Erlotinib is a targeted treatment for advanced non-small cell lung cancer. Smoking status may be one of influencing factors of the efficacy of erlotinib. The aim of this study is to explore the impact of smoking status on the efficacy of erlotinib in patients with advanced non-small cell lung cancer. Methods Patients with nonsmall cell lung cancer who had been previously treated with at least one course of platinum based chemotherapy received 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression-free survival, overall survival were analyzed in the different smoking status groups. Kaplan-Meier method was used to analyze the survival rate. Results Fortyeight patients were enrolled into the study from December 2005 to September 2006. We followed up these patients until 28th December, 2008. Median follow up time was 30 months. The compliance rate was 100%. The response rate was 32.1% in the smoking group and 35% in the never smoking group (P=0.836); The median progression-free survival was 3 months and 9 months, respectively (P=0.033). The median overall survival was 5 months and 17 months, respectively (P=0.162). Conclusion Erlotinib is an effective drug for advanced non-small cell lung cancer patients with different smoking status. Progressionfree survival is better in the never smoking patients than the smoking patients

Analysis of Differentially Expressed Proteins in Self-Paired Sera of Advanced Non-small Cell Lung Cancer Patients Responsive to Gefin

Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy. The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted therapy in advanced non-small cell lung cancer. Methods Twenty self-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control (SD or PR) after gefinitib therapy, at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress. All samples were pre-separated by WCX microbeads, and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM. ClinProTools (Version: 2.1) was used to analyze the differentially expressed proteins. Results There were 7 protein peaks (m/z), 3242.09, 8 690.36, 2 952.64, 3 224.04, 1 450.51, 1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples. Three proteins (3 242.09, 2 952.64 and 3 224.04) were down-regulated and four proteins (8 690.36, 1 450.51, 1 887.8 and 3 935.73) up-regulated in gefinitib treated sera. Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance, yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation

Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression

<p>Abstract</p> <p>Background</p> <p>The anaplastic lymphoma kinase (<it>ALK</it>) gene is frequently involved in translocations that lead to gene fusions in a variety of human malignancies, including lymphoma and lung cancer. Fusion partners of <it>ALK </it>include <it>NPM</it>, <it>EML4</it>, <it>TPM3</it>, <it>ATIC</it>, <it>TFG</it>, <it>CARS</it>, and <it>CLTC</it>. Characterization of ALK fusion patterns and their resulting clinicopathological profiles could be of great benefit in better understanding the biology of lung cancer.</p> <p>Results</p> <p>RACE-coupled PCR sequencing was used to assess <it>ALK </it>fusions in a cohort of 103 non-small cell lung carcinoma (NSCLC) patients. Within this cohort, the <it>EML4</it>-<it>ALK </it>fusion gene was identified in 12 tumors (11.6%). Further analysis revealed that <it>EML4</it>-<it>ALK </it>was present at a frequency of 16.13% (10/62) in patients with adenocarcinomas, 19.23% (10/52) in never-smokers, and 42.80% (9/21) in patients with adenocarcinomas lacking <it>EGFR </it>and <it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion was associated with non-smokers (<it>P </it>= 0.03), younger age of onset (<it>P </it>= 0.03), and adenocarcinomas without <it>EGFR</it>/<it>KRAS </it>mutations (<it>P </it>= 0.04). A trend towards improved survival was observed for patients with the <it>EML4</it>-<it>ALK </it>fusion, although it was not statistically significant (<it>P </it>= 0.20). Concurrent deletion in <it>EGFR </it>exon 19 and fusion of <it>EML4</it>-<it>ALK </it>was identified for the first time in a Chinese female patient with an adenocarcinoma. Analysis of ALK expression revealed that ALK mRNA levels were higher in tumors positive for the <it>EML</it>-<it>ALK </it>fusion than in negative tumors (normalized intensity of 21.99 vs. 0.45, respectively; <it>P </it>= 0.0018). However, expression of EML4 did not differ between the groups.</p> <p>Conclusions</p> <p>The <it>EML4</it>-<it>ALK </it>fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking <it>EGFR</it>/<it>KRAS </it>mutations. The <it>EML4</it>-<it>ALK </it>fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of <it>EML4</it>-<it>ALK</it>-positive patients.</p

Distribution of CRISPR Types in Fluoroquinolone-Resistant Campylobacter jejuni Isolates

To aid development of phage therapy against Campylobacter, we investigated the distribution of the clustered regularly interspaced short palindromic repeats (CRISPR) systems in fluoroquinolone (FQ)-resistant Campylobacter jejuni. A total of 100 FQ-resistant C. jejuni strains from different sources were analyzed by PCR and DNA sequencing to determine resistance-conferring mutation in the gyrA gene and the presence of various CRISPR systems. All but one isolate harbored 1–5 point mutations in gyrA, and the most common mutation was the Thr86Ile change. Ninety-five isolates were positive with the CRISPR PCR, and spacer sequences were found in 86 of them. Among the 292 spacer sequences identified in this study, 204 shared 93–100% nucleotide homology to Campylobacter phage D10, 44 showed 100% homology to Campylobacter phage CP39, and 3 had 100% homology with Campylobacter phage CJIE4-5. The remaining 41 spacer sequences did not match with any phages in the database. Based on the results, it was inferred that the FQ-resistant C. jejuni isolates analyzed in this study were potentially resistant to Campylobacter phages D10, CP39, and CJIE4-5 as well as some unidentified phages. These phages should be excluded from cocktails of phages that may be utilized to treat FQ-resistant Campylobacter

Experimental study on stepless capacity regulation for reciprocating compressor based on novel rotary control valve

A capacity-regulation system based on a novel rotary control valve for reciprocating refrigeration compressor is proposed and designed for the first time. The regulation system is mainly composed of a rotary control valve and an adaptive regulation system. The structure and working principle of the rotary control valve is described in detail, and the control process of the adaptive regulation system for the valve is studied together with the program design. In addition, the parameters for the design and control of the rotary control valve are theoretically determined. To verify the feasibility and effectiveness of the proposed system, a three-cylinder reciprocating compressor was adopted as a test device. Experimental results showed that the technology was able to realize continuous stepless capacity regulation for the compressor within the range of (0)10-100%, and power consumption decreased correspondingly with the load reduction. (C) 2013 Elsevier Ltd and IIR. All rights reserved