• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.2
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• pp.177-182
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• 2014

Purpose : The goal of this study was to compare and analysis the dose distribution and treatment time between Tomotherapy planning with fixed jaw(FJ) and dynamic jaw(DJ). Materials and Methods : Seven patients were selected in the study including five common clinical cases(brain, head and neck(HN), lung, prostate, spine). 1) Helical Tomotherapy plans with FJ and DJ were generated with the same planning parameters such as Modulation factor, Pitch and Field width. 2) Tomo_edge plans with a larger field width were generated to compare to conventional HT delivery with fixed jaw. Dosimetric evaluation indices for target coverage are Dmin, Conformity index(CI) and for whole body including target are $V_{10%}$, $V_{25%}$, $V_{50%}$, $V_{75%}$ using Dose-volume histogram(DVH). Also, Treatment time and Cumulative MU were used for clinical review on Tomo_edge. Results : In case of using the same field width of Tomotherapy planning with FJ and DJ, the averaged variations were $V_{10%}$: -11.91%, $V_{25%}$: -7.6%, $V_{50%}$ :-4.75%, $V_{75%}$: -1.04%. Tomo_edge with a larger field width provides the averaged variations for target coverage: Dmin: -0.72%, CI: -1.25% and also shows the tendency of a sharp $V_{x%}$ decline in low dose area. The clinical improvements in the larger field width with DJ were observed in the treatment time, ranging from -51.21% to -15.11, and the Cumulative MU decrease, ranging from -57.74% to -15.31%. Conclusion : Target coverage achieved by FJ and DJ with the same field width has little differences. But integral doses on whole body efficiently decreased. Compared to the conventional HT delivery, Tomo_edge with a larger field width presents a little worse target coverage. However, it provides faster treatment delivery and improved cranial-caudal target dose conformity. Therefore, Tomo_edge mode is efficient in improving the treatment time and integral dose while maintaining comparable plan quality in clinic.