Effects of EGFT-TKIs on Sequential Pemetrexed for Advanced Pulmonary Adenocarcinoma

Background and objective Pemetrexed and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) were used in patients with EGFR mutation to determine their effects. This study analyzed the influence of EGFR-TKIs on pemetrexed by observing the clinical efficacy and toxicity of pemetrexed following responses to EGFR-TKIs. Methods Pulmonary adenocarcinoma patients were divided into EGFR-TKIs and no-EGFR-TKI groups according to the targeted therapy. All patients received pemetrexed (500 mg/m2) as second (or higher)-line treatment. The Response Evaluation Criteria in Solid Tumors (version 1.0) were used to evaluate the response to pemetrexed. Adverse events were classified based on version 4.0 of the National Cancer Institute Common Toxicity Criteria. Results There were 57 patients in the EGFR-TKIs group and 56 in the no-EGFR-TKIs group. The disease control rates (DCRs) were 77.2% and 67.9% (P=0.367). The progression free survival (PFS) periods were 5.95 and 3.55 months (P=0.535). The overall survival (OS) periods were 10.10 and 8.24 months (P=0.432). However, these values were not statistically significant. The common toxicities of pemetrexed were hematologic and gastrointestinal (grades I and II). Two patients in the EGFR-TKIs group discontinued pemetrexed because of severe toxicities, which were not observed in the no-EGFR-TKIs group. Both groups had one patient who reduced dosage because of myelosuppression (grade IV). There were five and nine patients in the EGFR-TKIs and no-EGFR-TKIs groups, respectively, who delayed therapy not because of severe toxicities but due to subjective factors. Conclusion The DCRs, PFS periods, and OS periods of the patients administered with pemetrexed following EGFR-TKIs were better than those of the EGFR-TKIs group, but the differences were not statistically significant. Therefore, sequential pemetrexed administration caused negligible toxicities and can be used in adenocarcinoma therapy following responses to EGFR-TKIs

LncRNA-MSC-AS1 inhibits the ovarian cancer progression by targeting miR-425-5p

Abstract Background Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were reported to be aberrantly expressed and related to the pathogenesis of ovarian cancer. However, the role and regulatory mechanism of MSC-AS1 in ovarian cancer has yet to be fully elucidated. Methods Expression of lncRNA MSC-AS1 (MSC-AS1) and microRNA-425-5p (miR-425-5p) in the ovarian cancer tissue samples and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The functions of MSC-AS1 on ovarian cancer cell proliferation, cell cycle and apoptosis were determined using MTT, colony formation and flow cytometry analyses. The protein expression levels were evaluated using western blot assay. The targeting relationship MSC-AS1 and miR-425-5p was verified via dual-luciferase reporter assay. Results MSC-AS1 expression level was lowly expressed, while miR-425-5p level was highly in ovarian cancer tissues and cells. Elevation of MSC-AS1 has the ability to significantly inhibit cell proliferation and facilitate cell apoptosis in SKOV3 and A2780 cells. Moreover, MSC-AS1 targeted and negatively modulated miR-425-5p. MiR-425-5p up-regulation has been proved to partially reverse the tumor suppressive function of MSC-AS1 overexpression Conclusion MSC-AS1 sponged miR-425-5p to inhibit the ovarian cancer progression. These findings may provide a promising therapeutic target for the treatment of ovarian cancer

Network analysis of gene essentiality in functional genomics experiments

Many genomic techniques have been developed to study gene essentiality genome-wide, such as CRISPR and shRNA screens. Our analyses of public CRISPR screens suggest protein interaction networks, when integrated with gene expression or histone marks, are highly predictive of gene essentiality. Meanwhile, the quality of CRISPR and shRNA screen results can be significantly enhanced through network neighbor information. We also found network neighbor information to be very informative on prioritizing ChIP-seq target genes and survival indicator genes from tumor profiling. Thus, our study provides a general method for gene essentiality analysis in functional genomic experiments (http://nest.dfci.harvard.edu). Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0808-9) contains supplementary material, which is available to authorized users

Transcriptomic and Metabolomic Analysis Revealed Multifaceted Effects of Phage Protein Gp70.1 on Pseudomonas aeruginosa

The impact of phage infection on the host cell is severe. In order to take over the cellular machinery, some phage proteins were produced to shut off the host biosynthesis early in the phage infection. The discovery and identification of these phage-derived inhibitors have a significant prospect of application in antibacterial treatment. This work presented a phage protein, gp70.1, with nonspecific inhibitory effects on Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). Gp70.1 was encoded by early gene – orf 70.1 from P. aeruginosa phage PaP3. The P. aeruginosa with a plasmid encoding gp70.1 showed with delayed growth and had the appearance of a small colony. The combination of multifaceted analysis including microarray-based transcriptomic analysis, RT-qPCR, nuclear magnetic resonance (NMR) spectroscopy-based metabolomics and phenotype experiments were performed to investigate the effects of gp70.1 on P. aeruginosa. A total of 178 genes of P. aeruginosa mainly involved in extracellular function and metabolism were differentially expressed in the presence of gp70.1 at 3 examined time points. Furthermore, our results indicated that gp70.1 had an extensive impact on the extracellular phenotype of P. aeruginosa, such as motility, pyocyanin, extracellular protease, polysaccharide, and cellulase. For the metabolism of P. aeruginosa, the main effect of gp70.1 was the reduction of amino acid consumption. Finally, the RNA polymerase sigma factor RpoS was identified as a potential cellular target of gp70.1. Gp70.1 was the first bacterial inhibitor identified from Pseudomonas aeruginosa phage PaP3. It was also the first phage protein that interacted with the global regulator RpoS of bacteria. Our results indicated the potential value of gp70.1 in antibacterial applications. This study preliminarily revealed the biological function of gp70.1 and provided a reference for the study of other phage genes sharing similarities with orf70.1

Additional file 1: of Network analysis of gene essentiality in functional genomics experiments

Supplementary methods, Supplementary Figures S1 to S12 and Tables S1 and S2. (PDF 524 kb