Chang W Song1, Yoon-Jin Lee2, Robert J Griffin3, Inhwan Park4, Nathan A Koonce3, Susanta Hui4, Mi-Sook Kim2, Kathryn E Dusenbery4, Paul W Sperduto5, L Chinsoo Cho4. 1. Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota; Korea Institute of Radiological and Medical Sciences, Seoul, Korea. Electronic address: songx001@umn.edu. 2. Korea Institute of Radiological and Medical Sciences, Seoul, Korea. 3. Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas. 4. Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota. 5. Minneapolis Radiation Oncology and Gamma Knife Center, University of Minnesota, Minneapolis, Minnesota.
Abstract
PURPOSE: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). METHODS AND MATERIALS: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo--in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. RESULTS: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. CONCLUSIONS: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.
PURPOSE: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). METHODS AND MATERIALS: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo--in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. RESULTS: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. CONCLUSIONS: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of humantumors with SBRT and SRS.
Authors: Robert Timmerman; Rebecca Paulus; James Galvin; Jeffrey Michalski; William Straube; Jeffrey Bradley; Achilles Fakiris; Andrea Bezjak; Gregory Videtic; David Johnstone; Jack Fowler; Elizabeth Gore; Hak Choy Journal: JAMA Date: 2010-03-17 Impact factor: 56.272
Authors: Michael Staehler; Markus Bader; Boris Schlenker; Jozefina Casuscelli; Alexander Karl; Alexander Roosen; Christian G Stief; Axel Bex; Berndt Wowra; Alexander Muacevic Journal: J Urol Date: 2014-08-14 Impact factor: 7.450
Authors: Sunil Sharma; Ganesh Narayanasamy; Beata Przybyla; Jessica Webber; Marjan Boerma; Richard Clarkson; Eduardo G Moros; Peter M Corry; Robert J Griffin Journal: Technol Cancer Res Treat Date: 2016-07-08
Authors: M Protopapa; V Kouloulias; A Kougioumtzopoulou; Z Liakouli; C Papadimitriou; A Zygogianni Journal: Clin Transl Oncol Date: 2019-06-28 Impact factor: 3.405
Authors: Shelby Lennon; Ayman Oweida; Dallin Milner; Andy V Phan; Shilpa Bhatia; Benjamin Van Court; Laurel Darragh; Adam C Mueller; David Raben; Jorge L Martínez-Torrecuadrada; Todd M Pitts; Hilary Somerset; Kimberly R Jordan; Kirk C Hansen; Jason Williams; Wells A Messersmith; Richard D Schulick; Philip Owens; Karyn A Goodman; Sana D Karam Journal: Clin Cancer Res Date: 2019-04-03 Impact factor: 12.531
Authors: David G Kirsch; Max Diehn; Aparna H Kesarwala; Amit Maity; Meredith A Morgan; Julie K Schwarz; Robert Bristow; Sandra Demaria; Iris Eke; Robert J Griffin; Daphne Haas-Kogan; Geoff S Higgins; Alec C Kimmelman; Randall J Kimple; Isabelle M Lombaert; Li Ma; Brian Marples; Frank Pajonk; Catherine C Park; Dörthe Schaue; Phuoc T Tran; Eric J Bernhard Journal: J Natl Cancer Inst Date: 2018-04-01 Impact factor: 13.506
Authors: Nathan A Koonce; Mazen A Juratli; Chengzhong Cai; Mustafa Sarimollaoglu; Yulian A Menyaev; Judith Dent; Charles M Quick; Ruud P M Dings; Dmitry Nedosekin; Vladimir Zharov; Robert J Griffin Journal: Biochem Biophys Res Commun Date: 2017-08-16 Impact factor: 3.575
Authors: Jordan A Torok; Patrick Oh; Katherine D Castle; Michael Reinsvold; Yan Ma; Lixia Luo; Chang-Lung Lee; David G Kirsch Journal: Cancer Res Date: 2018-10-12 Impact factor: 12.701