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Purpose: To identify genes responsible for the radiosensitivity, we investigated the role of the differential gene expression profiles by comparing radioresistant H1299 with radiosensitive H460 lung cancer cell lines. Materials and methods: mRNA profiles of lung cancer cell lines were assessed using microarray, and subsequent validation was performed with qRT-PCR (Quantitative real time-polymerase chain reaction). The expression levels of differentially expressed genes were determined by Western blot and the radioresistance of lung cancer cell lines was measured by clonogenic assay. Results: From the differentially expressed apoptosis-related genes between H1299 and H460, we found Dcr3 (Decoy receptor 3, also known as TNFRSF6B; Tumour necrosis factor receptor super family member 6B) expression was significantly (P=4.38 x 10 (7)) higher in H1299 cells than H460 cells. Moreover, the Dcr3 mRNA expression level in the radioresistant cell lines (H1299, A549, DLD1, MB231, MB157) was increased in comparison to the radiosensitive cell lines (ME180, Caski, U87MG, MCF7, H460). Overexpression of Dcr3 increased the survival rate of radiosensitive H460, MCF7, and U87MG cells, and knockdown of Dcr3 abolished the radioresistance of A549 cells. The survival rate of p53 (Tumour protein 53)-deficient H1299 after gamma-irradiation was not affected by the suppression of Dcr3 expression. However, when we introduced p53 into H1299 cells, siDcr3 (siRNA of Dcr3) suppressed the radioresistance of H1299 cells by inducing p53-dependent Fas (Fas receptor, also known as TNFRSF6; Tumour necrosis factor receptor super family member 6)-mediated apoptosis pathway. Conclusion: Characterisation of gene expression profiles in two lung cancer cell lines revealed that Dcr3 expression and p53-dependent apoptosis signalling pathway regulate cellular response to ionising radiation. ; This paper was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean Government (MOST; M20706000020- 07M0600-02010; W-Y. Park), the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs (A084022) and Brain Korea21 (BK21) Program (S-H. Jung and W-Y. Park). ; Chaudhry MA, 2008, J BIOMED SCI, V15, P557, DOI 10.1007/s11373-008-9253-z ; Toscano F, 2008, ONCOGENE, V27, P4161, DOI 10.1038/onc.2008.52 ; Aravindan N, 2008, MOL CELL BIOCHEM, V310, P167, DOI 10.1007/s11010-007-9678-0 ; Chaudhry MA, 2008, J BIOMED BIOTECHNOL, DOI 10.1155/2008/541678 ; Hayashi S, 2007, ARTHRITIS RHEUM, V56, P1067, DOI 10.1002/art.22494 ; Ogawa K, 2006, INT J ONCOL, V28, P705 ; Liu XG, 2005, CANCER RES, V65, P9169, DOI 10.1158/0008-5472.CAN-05-0939 ; Guo WF, 2005, RADIAT RES, V164, P27 ; Nix P, 2005, BRIT J CANCER, V92, P2185, DOI 10.1038/sj.bjc.6602647 ; Viktorsson K, 2005, BIOCHEM BIOPH RES CO, V331, P868, DOI 10.1016/j.bbrc.2005.03.192 ; Fukuda K, 2004, BRIT J CANCER, V91, P1543, DOI 10.1038/sj.bjc.6602187 ; Harima Y, 2004, INT J RADIAT ONCOL, V60, P237, DOI 10.1016/j.ijrobp.2004.02.047 ; Kelley SK, 2004, CURR OPIN PHARMACOL, V4, P333, DOI 10.1016/j.coph.2004.02.006 ; Dunne AL, 2003, BRIT J CANCER, V89, P2277, DOI 10.1038/sj.bjc.6601427 ; Dent P, 2003, RADIAT RES, V159, P283 ; Park WY, 2002, ONCOGENE, V21, P8521 ; Grace MB, 2002, INT J RADIAT BIOL, V78, P1011, DOI 10.1080/09553000210158056 ; Kitahara O, 2002, NEOPLASIA, V4, P295 ; Embree-Ku M, 2002, BIOL REPROD, V66, P1456, DOI 10.1095/biolreprod66.5.1456 ; Sheard MA, 2001, INT J CANCER, V96, P213 ; Hanna E, 2001, CANCER RES, V61, P2376 ; Bernhard EJ, 2000, CANCER RES, V60, P6597 ; Amundson SA, 2000, RADIAT RES, V154, P342 ; Maecker HL, 2000, CANCER RES, V60, P4638 ; Park WY, 2000, J BIOL CHEM, V275, P20847 ; Maebayashi K, 1999, INT J RADIAT ONCOL, V44, P677 ; Ashkenazi A, 1999, CURR OPIN CELL BIOL, V11, P255 ; Matsumura Y, 1997, CANCER LETT, V115, P91 ; Hsiao M, 1997, BIOCHEM BIOPH RES CO, V233, P329 ; Riva C, 1995, ORAL ONCOL, V31B, P384 ; BIARD DSF, 1994, CANCER RES, V54, P3361 ; SLICHENMYER WJ, 1993, CANCER RES, V53, P4164 ; BRACHMAN DG, 1993, CANCER RES, V53, P3667 ; LEE JM, 1993, P NATL ACAD SCI USA, V90, P5742 ; SKLAR MD, 1988, SCIENCE, V239, P645 ; 2

Background The aim of this study was to compare the plan quality of magnetic-resonance image-based intensity modulated radiation therapy (MRI-based-IMRT) with the MRIdian Linac system to that of volumetric modulated arc therapy (VMAT) with the TrueBeam STx system for lung stereotactic ablative radiotherapy (SABR). Methods A total of 22 patients with tumors located in the lower lobe were retrospectively selected for the study. For each patient, both the MRI-based-IMRT and VMAT plans were generated using an identical CT image set and identical structures with the exception of the planning target volume (PTV). The PTVs of the MRI-based-IMRT were generated by adding an isotropic margin of 3 mm from the gross tumor volume, whereas those of VMAT were generated by adding an isotropic margin of 5 mm from the internal target volume. For both the MRI-based-IMRT and VMAT, the prescription doses to the PTVs were 60 Gy in four fractions. Results The average PTV volume of the MRI-based-IMRT was approximately 4-times smaller than that of VMAT (p < 0.001). The maximum dose to the bronchi for the MRI-based-IMRT was smaller than that for the VMAT (20.4 Gy versus 24.2 Gy, p < 0.001). In addition, V40Gy of the rib for the MRI-based-IMRT was smaller than that for the VMAT (1.8 cm3 versus 7.7 cm3, p = 0.008). However, the maximum doses to the skin and spinal cord for the MRI-based-IMRT (33.0 Gy and 14.5 Gy, respectively) were larger than those for the VMAT (27.8 Gy and 11.0 Gy, respectively) showing p values of less than 0.02. For the ipsilateral lung, the mean dose, V20Gy, V10Gy, and V5Gy for the MRI-based-IMRT were smaller than those for the VMAT (all with p < 0.05). For the contralateral lung, V5Gy, V10Gy, D1500cc, and D1000cc for the MRI-based-IMRT were larger than those for the VMAT (all with p < 0.05). The mean dose and V50% of the whole body for the MRI-based-IMRT were smaller than those for the VMAT (0.9 Gy versus 1.2 Gy, and 78.7 cm3 versus 103.5 cm3, respectively, all at p < 0.001). Conclusions The MRI-based-IMRT using the MRIdian Linac system could reduce doses to bronchi, rib, ipsilateral lung, and whole body compared to VMAT for lung SABR when the tumor was located in the lower lobe. ; This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2017M2A2A7A02020640, 2017M2A2A7A02020641, and 2017M2A2A7A02020643).

Background This study set out to evaluate the effect of dose rate on normal tissues (the lung, in particular) and the variation in the treatment efficiency as determined by the monitor unit (MU) and energy applied in Linac-based volumetric arc therapy (VMAT) total marrow irradiation (TMI). Methods Linac-based VMAT plans were generated for the TMI for six patients. The planning target volume (PTV) was divided into six sub-volumes, each of which had their own isocenter. To examine the effect of the dose rate and energy, a range of MU rates (40, 60, 80, 100, 300, and 600 MU/min) were selected for 6, 10, and 15 MV. All the plans were verified by portal dosimetry. Results The dosimetric parameters for the target and normal tissue were consistent in terms of the energy and MU rate. The beam-on time was changed from 59.6 to 6 min for 40 and 600 MU/min. When 40 MU/min was set for the lung, the dose rate delivered to the lung was less than 6 cGy/min (that is, 90%), while the beam-on time was approximately 10 min. The percentage volume of the lung receiving 20 cGy/min was 1.47, 3.94, and 6.22% at 6, 10, and 15 MV, respectively. However, for 600 MU/min, the total lung volume received over 6 cGy/min regardless of the energy, and over 20 cGy/min for 10 and 15 MV (i.e., 54.4% for 6 MV). Conclusions In TMI treatment, reducing the dose rate administered to the lung can decrease the incidence of pulmonary toxicity. To reduce the probability of normal tissue complications, the selection of the lowest MU rate is recommended for fields including the lung. To minimize the total treatment time, the maximum MU rate can be applied to other fields. ; This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (no. 2017M2A2A7A02020641) and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (no. HA 16C0025).

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. ; Abstract Background Treatment of tonsil cancer, a subset of oropahryngeal cancer, varies between surgery and radiotherapy. Well-designed studies in tonsil cancer have been rare and it is still controversial which treatment is optimal. This study aimed to assess the outcome and failure patterns in tonsil cancer patients treated with either approaches. Methods We retrospectively reviewed medical records of 586 patients with tonsil cancer, treated between 1998 and 2010 at 16 hospitals in Korea. Two hundred and one patients received radiotherapy and chemotherapy (CRT), while 385 patients received surgery followed by radiotherapy and/or chemotherapy (SRT). Compared with the SRT group, patients receiving CRT were older, with more advanced T stage and received higher radiotherapy dose given by intensity modulation techniques. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and clinicopathologic factors were analyzed. Results At follow-up, the 5-year OS, DFS, LRRFS and DMFS rates in the CRT group were 82, 78, 89, and 94%, respectively, and in the SRT group were 81, 73, 87, and 89%, respectively. Old age, current smoking, poor performance status, advanced T stage, nodal involvement, and induction chemotherapy were associated with poor OS. Induction chemotherapy had a negative prognostic impact on OS in both treatment groups (p = 0.001 and p = 0.033 in the CRT and SRT groups, respectively). Conclusions In our multicenter, retrospective study of tonsil cancer patients, the combined use of radiotherapy and chemotherapy resulted in comparable oncologic outcome to surgery followed by postoperative radiotherapy, despite higher-risk patients having been treated with the definitive radiotherapy. Induction chemotherapy approaches combined with either surgery or definitive radiotherapy were associated with unfavorable outcomes. ; This research was supported by a grant from the National Research Foundation of Korea (NRF), which is funded by the Korean government (MEST, grant no.2015M2A2A7055063); a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (H14C3459); and the National R&D Program through the Dong-nam Institute of Radiological and Medical Sciences (DIRAMS) funded by the Ministry of Education, Science, and Technology (50595–2016). The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.