Statins, HMG-CoA reductase inhibitors have been studied for their antiproliferative and proapototic effects. Recently, statin-induced apoptosis has been associated with down-regulation of survivin expression in cancer cells. However, the mechanism of deregulated survivin by simvastatin on lung cancer is still unclear. Herein, we demonstrated that simvastatin induced caspase-dependent apoptosis in A549 lung cancer cells. Simvastatin also resulted in a decrease in the expression of phosphorylated Akt. In addition, simvastatin effectively down-regulated survivin mRNA and protein, but not cIAP-1 and cIAP-2. The combination of simvastatin and 10 μM LY294002 (non-toxic dose) augmented apoptosis significantly, as evidenced by cleavage of PARP. The immunoreactive band of survivin was markedly decreased in cells treated with 50 μM LY294002 (toxic dose) as well as by the combination of simvastatin and 10 μM LY294002. Moreover, survivin down-regulation by RNA interference induced apoptosis accompanied by an increase in hypodiploid DNA content. Taken together, these data suggest that the anti-cancer effect of simvastatin via induction of apoptosis is related to Akt signaling dependent down-regulation of survivin in lung cancer A549 cells.

BackgroundSerine/arginine-rich splicing factors (SRSFs) and HNRNPA1 have oncogenic properties. However, their proteomic expressions and practical priority in gastric cancer (GC) and colorectal cancer (CRC) are mostly unknown. To apply SFs in clinics, effective marker selection and characterization of properties in the target organ are essential.MethodsWe concurrently analyzed SRSF1, 3, and 5–7, and HNRNPA1, together with the conventional tumor marker carcinoembryonic antigen (CEA), in stomach and colorectal tissue samples (n = 420) using semiquantitative immunoblot, subcellular fractionation, and quantitative real-time polymerase chain reaction methods.ResultsIn the semiquantitative immunoblot analysis, HNRNPA1 and SRSF7 levels were significantly higher in GC than in gastric normal mucosa, and SRSF7 levels were higher in intestinal-type compared with diffuse-type of gastric adenocarcinoma. Of the SFs, only HNRNPA1 presented greater than 50 % upregulation (cancer/normal mucosa > 2-fold) incidences and CEA-comparable, acceptable (>70 %) detection accuracy (74 %) for GC. All SF protein levels were significantly higher in CRC than in colorectal normal mucosa, and HNRNPA1 levels were higher in low-stage CRC compared with high-stage CRC. Among the SFs, HNRNPA1 and SRSF3 presented the two highest upregulation incidences (88 % and 74 %, respectively) and detection accuracy (90 % and 84 %, respectively) for CRC. The detection accuracy of HNRNPA1 was comparable to that of CEA in low (≤ II)-stage CRC but was inferior to that of CEA in high (>II)-stage CRC. Extranuclear distributions of HNRNPA1 and SRSF6 (cytosol/microsome) differed from those of other SRSFs (membrane/organelle) in both cancers. In an analysis of the six SF mRNAs, all mRNAs presented unacceptable detection accuracies (≤70 %) in both cancers, and all mRNAs except SRSF6 were disproportionate to the corresponding protein levels in GC.ConclusionOur results provide a comprehensive insight into the six SF expression profiles in GC and indicate that, among the SFs, HNRNPA1, but not HNRNPA1 mRNA, is the most effective, novel GC marker. Regardless of the good to excellent detection accuracy of SRSF3 and HNRNPA1 in CRC, the SFs have lower practical priority than CEA, especially for high-stage CRC detection.

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Our results identified that HNRNPA1 is the best diagnostic marker among the SFs and conventional markers given its excellent diagnostic efficacy for cervical carcinoma, and it has a p16-comparable diagnostic value. We suggest that HNRNPA1 is an additional effective target protein for developing cervical cancer detection tools.

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Survivin has been shown to inhibit apoptosis, enhance proliferation and promote angiogenesis. This study aimed to identify diagnostic value of survivin protein in malignant pleural effusion (MPE) and to investigate the prediction of response to chemotherapy and the prognostic role on pleural survivin in lung cancer patients with MPE. Pleural effusion samples were collected from 67 patients with MPE (58 lung cancers; 9 extrathoracic tumors), and from 68 patients with benign conditions (31 with pneumonia; 37 with tuberculosis). Concentrations of pleural fluid survivin, Cyfra 21-1, and carcinoembryonic antigen (CEA) were measured by enzyme-linked immunosorbent assay. The expression profile of survivin in pleural fluid, and its association with survival, were investigated. Survivin levels were significantly elevated in patients with MPE, especially primary lung cancer than in those of benign origin. Survivin, Cyfra 21-1, and CEA varied in diagnostic accuracy for differentiating MPE from benign pleural effusion by 67.5, 68.3, and 93.4%, respectively. Lung cancer patients with MPE who were positive for survivin expression were more refractory to chemotherapy (P = 0.003). Positive for survivin expression was correlated with a reduced overall survival in univariate (P = 0.0001) and multivariate (P = 0.004) analyses. Using the appropriate cut-off points, CEA in pleural fluid has a higher accuracy than other tumor markers, and that survivin has a low diagnostic accuracy for differentiating MPE from benign pleural effusion. Our findings suggest that positive survivin expression may be used as a predictor of a poor response to chemotherapy and shorter survival in lung cancer patients with MPE.

First-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for patients with advanced non-small cell lung cancer who were selected on the basis of EGFR mutations have improved the progression-free survival with acceptable toxicity compared to standard chemotherapy. However, acquired resistance to EGFR-TKIs has been identified as an important clinical problem. Transformation to small cell lung cancer (SCLC) is a rare mechanism of resistance to EGFR-TKI therapy. We describe the case of a 61-year-old man who presented transformation from adenocarcinoma to SCLC as the manifestation of acquired resistance after EGFR-TKI treatment. He underwent chemotherapy with etoposide and cisplatin and achieved a complete response.

Malignant melanoma occurs most frequently on the skin. However, it can also arise in other organs and tissues of the body. Primary pulmonary malignant melanoma is a very rare non-epithelial neoplasm accounting for 0.01% of all primary pulmonary tumors. The treatment of choice is surgical resection of the tumor with an oncologically adequate margin as in lobectomy or pneumonectomy. The prognosis of this condition is rather poor. Based on previous data, its 5-year survival is at least 10%. Here, we report a case of an 82-year-old woman whose primary pulmonary melanoma was detected incidentally.