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Purpose Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventive or chemotherapeutic agents. The mechanism underlying the deregulation of survivin by NSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. In this study, we investigated the synergistic interaction of sulindac and simvastatin in lung cancer A549 cells. Materials and Methods Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells. Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDA and MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. The effects of AKT on survivin expression in sulindac- and simvastatin-treated cells were assessed. Survivin was knocked down or overexpressed to determine its role in apoptosis induced by sulindac and simvastatin. Results Sulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROS production in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, while AKT overexpression markedly increased survivin expression, even in the presence of sulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininduced apoptosis. In contrast, survivin upregulation protected against sulindac- and simvastatin-induced apoptosis. Conclusion Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. These results indicate that sulindac and simvastatin may be clinically promising therapies for the prevention of lung cancer.

Background: DNA content analysis of human solid tumor is now widely performed by flow cytometric study. One of the most interesting and potentially important observation in this field is that proliferative activity(S-Phase fraction of cell cycle) may profoundly affect prognosis. Method: S-Phase fraction(SPF) have been measured by flow cytometric method using tumor cells isolated from paraffin embedded tissue. To evaluate the prognostic significance, SPF of squamous lung cancer cell was assessed in 21 patients who died without any specific treatment. Results: 1) Mean survival time of squamous lung cancer patients was 225() days. Survival time were shortened, when TNM stage and PS scale were advanced. 2) Mean value of SPF of squamous lung cancer patients was 23.4()%. SPF had nothing to do with advance of TNM stage and PS scale. 3) Mean survival time of high SPF group(more than 20% of cell proliferation cycle) and low SPF group were 153() days and 342() days(p

연구배경 : 대량 객혈은 기도폐색의 위험이 높은 응급 상황이므로, 지혈을 위한 방법이 즉시 동원되어야 한다. 기관지동맥등의 폐순환동맥 색전술은 대량 객혈의 출혈부위 확인과 함께 신속히 지혈시킬 수 있는 방법이다. 저자들은 대량 객혈 환자에서 동맥 색전술을 시행하여 지혈의 효과와 출혈의 재발에 대하여 경과 관찰하였다. 방법 : 1990년 6월부터 1992년 7월까지 동맥 색전술을 시행하고나서 최소 6개월이상의 경과 관찰이 가능한 23명의 환자를 대상으로 하였다. 대퇴 동맥을 통한 경피적 삽관으로, 기관지동맥외에 비기관지 체측부동맥을 전부 혈관 조영하여 출혈 부위를 확인하고, 출혈부위 동맥에 gelfoam으로 색전하고, 출혈이 큰 경우에는 금속 제재인 coil을 함께 색전시켰다. 결과 : 23예 전예에서 즉각적인 지혈 효과를 볼 수 있었고, 7예(30%) 에서 재발하였다. 비기관지동맥 출혈군과 기관지동맥 단독출혈군의 재발률은 46% (6/13)와, 10% (1/10)로서 서로 비교되었다. 재발의 원인 질환은 비활동성 폐결핵 4예, 활동성 폐결핵 1예, 기관지 확장증 1예, 국균종 1예였으며, 조치로서 1예는 경과 관찰, 2예는 재색전, 2예는 재색전후 수술, 2예는 대량 객혈로 사망하였으며, coil로 색전한 경우는 아직 재발이 없었다. 결론 : 폐순환 동맥색전술은 대량 객혈 환자에서 장기간의 지혈 효과는 확실치 않으나, 응급적 조치로서는 확실한 지혈 효과가 있으며, 응급적 지혈후에는 원인 질환에 대한 대책을 즉시 수렵해야한다. 【Background: Massive hemoptysis that may induce acute asphyxia can be a fatal problem. Bronchial arteries and other nonbronchial systemic arteries of lungs must be searched by angiography, because they are main source of hemoptysis. Arterial embolization is a well-accepted and widely used for management of massive hemoptysis. This study was designed to evaluate the effectiveness of this method. Method: Prospective analysis was done in 23 cases, that underwent arterial embolization from June 1990 to July 1992. Hemorrhaged arteries were embolized with Gelfoam particles. In cases with severe broad hemorrhagic findings, Coils were added to Gelfoam particles. And they were observed for 6 months at least. Results: Immediate cessation of hemoptysis was achieved in all cases. Recurrent hemoptysis was observed in 7 cases (30%). The patients with nonbronchial artery hemoptysis had increased tendency of recurrence (6/13) than only bronchial artery hemotysis (1/10). The 7 cases treated with Coils had not any recurrence. Conclusion: Arterial embolization in massive hemoptysis is a useful and safe procedure for immediate control. But, the patients with this procedure had a potentiality of recurrence. So diagnostic and therapeutic efforts for underlying causes should be performed.】