ObjectiveTo investigate the molecular pathogenesis of pulmonary fibrosis induced by bleomycin in a murine model,and provide novel insights for clinical diagnosis and treatment. MethodsFrom Gene Expression Omnibus,we downloaded microarray data extracted from experiments of bleomycin induced pulmonary fibrosis in wild-type mice. With BRB-Array Tools,differentially expressed genes at different time points during disease development were screened,selected and analyzed by DAVID software. ResultsBRB array analysis identified 45101 differentially expressed genes. After induction by bleomycin on 7th day,1164 genes and 735 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. On 14th day,731 genes and 390 genes were significantly up-regulated and down-regulated (P<0.05,fold change>2),respectively. DAVID analysis revealed that the up-regulated genes were significantly enriched in cell cycle,p53 signaling and chemokine signaling pathway,damaging reaction and collagen metabolism gene sets. While the down-regulated genes were enriched in the drug metabolism pathway gene set. ConclusionsBioinformatics methodologies are able to efficiently analyze microarray data and extract its underlying information,provide novel insights for major molecular events and shift of cell signaling pathway during pulmonary fibrosis progression,and furthermore,finding molecular markers for early diagnosis and therapeutic targets.
ObjectiveTo summarize the progress in mechanisms of resistance to trastuzumab in treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. MethodsBy searching Pubmed and CNKI, the literatures of mechanisms of resistance to trastuzumab in treating HER2-positive breast cancer were reviewed. ResultsThe possible mechanism of resistance to trastuzumab are thought to include HER2 gene amplification and high protein expression; impaired access of trastuzumab to HER2; bidirectional crosstalk between ER and HER2; HER2 downstream signal transduction pathway activation; expansion expression of other RTKs and membrane-associated receptors; alterations in apoptosis and cell cycle control as well as multi-gene mutation, etc. ConclusionsMechanisms of trastuzumab resistance in HER2-positive breast cancer is complicated, a better understanding will be achieved by comprehensive analysis of existing possible mechanisms. The outcome of HER2-positive breast cancer patients who developed resistance to trastuzumab will be improved by appropriate multi-target regime.