Analysis of radiation therapy in a model of triple-negative breast cancer brain metastasis.

作者: DeeDee Smart , Alejandra Garcia-Glaessner , Diane Palmieri , Sarah J. Wong-Goodrich , Tamalee Kramp

DOI: 10.1007/S10585-015-9739-9

关键词:

摘要: Most cancer patients with brain metastases are treated radiation therapy, yet this modality has not been meaningfully incorporated into preclinical experimental metastasis models. We applied two forms of whole therapy (WBRT) to the brain-tropic 231-BR model triple-negative breast cancer. When compared sham controls, WBRT as 3 Gy × 10 fractions (3 10) reduced number micrometastases and large by 87.7 54.5 %, respectively (both p < 0.01); whereas a single dose 15 1 (15 1) was less effective, reducing 58.4 % (p 0.01) 47.1 = 0.41), respectively. Neuroinflammation in adjacent parenchyma due solely reaction from metastases, radiotherapy, while adult neurogenesis brains adversely affected following both regimens. The nature resistance investigated ex vivo culture tumor cells that survived initial ("Surviving" cultures). Surviving cultures surprisingly demonstrated increased radiosensitivity vivo. In contrast, re-injection re-treatment regimen significantly developed vivo, suggesting role for microenvironment. Micrometastases derived surviving trend toward radioresistance upon repeat treatment 0.09). data confirm potency fractionated identify microenvironment potential determinant efficacy. also nominate new translational radiotherapy.

参考文章(61)
Charles L. Limoli, Omar Bosch, Munjal M. Acharya, Vipan K. Parihar, Lori-Ann Christie, Dante E. Roa, Defining functional changes in the brain caused by targeted stereotaxic radiosurgery. Translational cancer research. ,vol. 3, pp. 124- 137 ,(2014) , 10.3978/J.ISSN.2218-676X.2013.06.02
Florian Heitz, Philipp Harter, Hans-Joachim Lueck, Annette Fissler-Eckhoff, Fatemeh Lorenz-Salehi, Stefanie Scheil-Bertram, Alexander Traut, Andreas du Bois, Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases European Journal of Cancer. ,vol. 45, pp. 2792- 2798 ,(2009) , 10.1016/J.EJCA.2009.06.027
Amol Ghia, Wolfgang A. Tomé, Sayana Thomas, George Cannon, Deepak Khuntia, John S. Kuo, Minesh P. Mehta, Distribution of Brain Metastases in Relation to the Hippocampus: Implications for Neurocognitive Functional Preservation International Journal of Radiation Oncology Biology Physics. ,vol. 68, pp. 971- 977 ,(2007) , 10.1016/J.IJROBP.2007.02.016
John R. Fike, Radoslaw Rola, Charles L. Limoli, Radiation response of neural precursor cells. Neurosurgery Clinics of North America. ,vol. 18, pp. 115- 127 ,(2007) , 10.1016/J.NEC.2006.10.010
Brunilde Gril, Diane Palmieri, Yongzhen Qian, Talha Anwar, David J. Liewehr, Seth M. Steinberg, Zoraida Andreu, Daniel Masana, Paloma Fernández, Patricia S. Steeg, Fernando Vidal-Vanaclocha, Pazopanib Inhibits the Activation of PDGFRβ-Expressing Astrocytes in the Brain Metastatic Microenvironment of Breast Cancer Cells American Journal of Pathology. ,vol. 182, pp. 2368- 2379 ,(2013) , 10.1016/J.AJPATH.2013.02.043
Jay Jagannathan, T. David Bourne, David Schlesinger, Chun-Po Yen, Mark E. Shaffrey, Edward R. Laws, Jason P. Sheehan, Clinical and pathological characteristics of brain metastasis resected after failed radiosurgery. Neurosurgery. ,vol. 66, pp. 208- 217 ,(2010) , 10.1227/01.NEU.0000359318.90478.69
Dean B. Percy, Emeline J. Ribot, Yuhua Chen, Catherine McFadden, Carmen Simedrea, Patricia S. Steeg, Ann F. Chambers, Paula J. Foster, In Vivo Characterization of Changing Blood-Tumor Barrier Permeability in a Mouse Model of Breast Cancer Metastasis: A Complementary Magnetic Resonance Imaging Approach Investigative Radiology. ,vol. 46, pp. 718- 725 ,(2011) , 10.1097/RLI.0B013E318226C427
Ana Olariu, Kathryn M. Cleaver, Heather A. Cameron, Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle. The Journal of Comparative Neurology. ,vol. 501, pp. 659- 667 ,(2007) , 10.1002/CNE.21268
Caroline I. Schnegg, Dana Greene-Schloesser, Mitra Kooshki, Valerie S. Payne, Fang-Chi Hsu, Mike E. Robbins, The PPARδ agonist GW0742 inhibits neuroinflammation, but does not restore neurogenesis or prevent early delayed hippocampal-dependent cognitive impairment after whole-brain irradiation Free Radical Biology and Medicine. ,vol. 61, pp. 1- 9 ,(2013) , 10.1016/J.FREERADBIOMED.2013.03.002
Debabrata Saha, Henry Dunn, Heling Zhou, Hiroshi Harada, Masahiro Hiraoka, Ralph P. Mason, Dawen Zhao, In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model Journal of Visualized Experiments. ,vol. 2011, pp. 3175- ,(2011) , 10.3791/3175