ABSTRACT
BACKGROUND@#Pneumonectomy and sleeve resection are routine operations for the treatment of central non-small cell lung cancer (NSCLC), but some patients suffered of central NSCLC, whose pulmonary function is too poor to tolerate pneumonectomy, or the tumor involves the bronchus and pulmonary artery extensively,it is hard to perform bronchovascular sleeve lobectomy. The aim of this study is to assess the feasibility of lung autotransplantation in the treatment of central NSCLC.@*METHODS@#The clinical data of 3 cases with central NSCLC treated by lung autotransplantation was reviewed from December 2016 to December 2018. One patient underwent double sleeve resection of left upper lobe with end-to-end anastomosis of the bronchus. Because the resection of the pulmonary artery was too long to perfrom a tension-free anastomosis, the inferior pulmonary vein was cut off, then the left lower lobe was moved up for an anastomosis of the inferior pulmonary vein and the stump of the superior pulmonary vein. In the other 2 cases, left pneumonectomy was performed directly, and the upper left lobe was excised in vitro. The lower left lobe was reset to the chest after trimming and flushing and then the bronchus, pulmonary artery and pulmonary vein were anastomosed in turn.@*RESULTS@#The average operation time was 333 min, the average time of vascular occlusion was 86 min, the average blood loss was 450 mL, and the average hospital stay was 18.7 d; Perioperative complications included a case of bronchial obstruction, which improved after sputum aspiration through bronchofibroscope. The average follow-up period was 20 mon; One case died of cancer, one case had recurrence of anastomotic stoma and brain metastasis, one case had 4R lymph node metastasis (stable condition after chemotherapy), and one case survived without recurrence.@*CONCLUSIONS@#For patients with central NSCLC with extensive tumor invasion, thus inability to tolerate sleeve resection or pneumonectomy, autologous lung transplantation can preserve lung function to the greatest extent with a complete tumor resection and improve postoperative quality of life.
ABSTRACT
Objective To analyze the differences in microRNA (miRNA) expression between A549 and A549/DDP cells and explore the association between miRNA expression and drug resistance in non-small cell lung cancer (NSCLC).Methods The drug resistance of A549/DDP cells was evaluated using CCK-8 assay and flow cytometry.Microarray technique and RT-PCR were used to analyze the differential expression of the miRNA between A549 and A549/DDP cells.Enforced or inhibited target miRNA expression in cisplatin resistant cell was used to investigate whether miRNA involve in modulating the sensitivity of NSCLC cells to chemotherapeutic agent,exploiting the emerging knowledge of miRNA for the development of new human therapeutic applications for overcoming anticancer drug resistance and trying to discover biomarkers that were better able to predict the cancer chemotherapy sensitivity.Results The drug resistance index of A549/DDP cells relative to the parental A549 cells was 18.Microarray analysis of A549 and A549/DDP cells identified 51 differentially expressed genes (≥4-fold),including 24 up-regulated and 27 down-regulated genes in A549/DDP cells.RT-PCR identified 9 miRNA that were differentially expressed between A549 and A549/DDP cells.Of these differentially expressed miRNA,miR-376c,miR-31,miR-29a,miR-221 showed significantly increased expression,and miR-196a,miR-20a,miR-20b,miR-17,miR-451 showed significantlylowered expression in A549/DDP cells as indicated by the results of microarray analysis and RT-PCR.DDP sensitivity was increased 11.7 ％ in A549/DDP cells transfected with miR-17,but the chemosensitivity was decreased when miR-451 was over-expressed or miR-29a was inhibited by selective inhibitor,the reduction was 15.5 ％,12.9 ％,respectively,whereas chemosensitivity did not change when miR-376c,miR-31,miR-221 were inhibited or miR-196a,miR-20b,miR-20a were over-expressed.Conclusion A549/DDP cells show a different miRNA expression profile from its parental A549 cells,suggesting the involvement of miRNA in tumor cell drug resistance.miR-17 has the potential to be an efficient agent for preventing and reversing DDP-resistance in NSCLC.These results provide a strong rationale for the development of miRNA-based therapeutic strategies aiming to overcome cancer cell resistance.
ABSTRACT
MicroRNAs (miRNAs) are a small noncoding family of 22 ut RNAs that play an important role in the negative regulation of gene expression at the post-transcriptional level by base pairing to the 3'untranslated region of target messenger RNAs.miRNAs are involved in a variety of basic processes,such as cell proliferation and apoptosis,metabolism and signaling pathways.A lot of studies have indeed described the aberrant expression of miRNAs in human tumors and have investigated their potential role as oncogenes or tumor suppressor genes,depending on the targets they regulate.Furthermore,more and more studies have demonstrated that an important role of miRNAs in anticancer drug resistance and miRNA expression profiling can correlate with the development of anticancer drug resistance.A systematic and intensive study on the mechanisms of miRNA in anticancer drug resistance will provide us a strong rationale for the development of miRNA-based therapeutic strategies aiming to overcome cancer cell resistance.This paper has reviewed the recent development of miRNAs involved in anticancer drug resistance.