Donna H Murrell1,2, Niloufar Zarghami2, Michael D Jensen2, Fiona Dickson1, Ann F Chambers2,3, Eugene Wong2,3, Paula J Foster1,2. 1. Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada. 2. Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. 3. London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada.
Abstract
PURPOSE: Incidence of brain metastasis attributed to breast cancer is increasing and prognosis is poor. It is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatments, thereby facilitating a mechanism for recurrence. Radiotherapy is used to treat brain metastases clinically, but assessment has been limited to macroscopic tumor volumes detectable by clinical imaging. Here, we use cellular MRI to understand the concurrent responses of metastases and nonproliferative or slowly cycling cancer cells to radiotherapy. METHODS: MRI cell tracking was used to investigate the impact of early cranial irradiation on the fate of individual iron-labeled cancer cells and outgrowth of breast cancer brain metastases in the human MDA-MB-231-BR-HER2 cell model. RESULTS: Early whole-brain radiotherapy significantly reduced the outgrowth of metastases from individual disseminated cancer cells in treated animals compared to controls. However, the numbers of nonproliferative iron-retaining cancer cells in the brain were not significantly different. CONCLUSIONS: Radiotherapy, when given early in cancer progression, is effective in preventing the outgrowth of solitary cancer cells to brain metastases. Future studies of the nonproliferative cancer cells' clonogenic potentials are warranted, given that their persistent presence suggests that they may have evaded treatment. Magn Reson Med 78:1506-1512, 2017.
PURPOSE: Incidence of brain metastasis attributed to breast cancer is increasing and prognosis is poor. It is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatments, thereby facilitating a mechanism for recurrence. Radiotherapy is used to treat brain metastases clinically, but assessment has been limited to macroscopic tumor volumes detectable by clinical imaging. Here, we use cellular MRI to understand the concurrent responses of metastases and nonproliferative or slowly cycling cancer cells to radiotherapy. METHODS: MRI cell tracking was used to investigate the impact of early cranial irradiation on the fate of individual iron-labeled cancer cells and outgrowth of breast cancer brain metastases in the human MDA-MB-231-BR-HER2 cell model. RESULTS: Early whole-brain radiotherapy significantly reduced the outgrowth of metastases from individual disseminated cancer cells in treated animals compared to controls. However, the numbers of nonproliferative iron-retaining cancer cells in the brain were not significantly different. CONCLUSIONS: Radiotherapy, when given early in cancer progression, is effective in preventing the outgrowth of solitary cancer cells to brain metastases. Future studies of the nonproliferative cancer cells' clonogenic potentials are warranted, given that their persistent presence suggests that they may have evaded treatment. Magn Reson Med 78:1506-1512, 2017.
Authors: Natalie J Serkova; Kristine Glunde; Chad R Haney; Mohammed Farhoud; Alexandra De Lille; Elizabeth F Redente; Dmitri Simberg; David C Westerly; Lynn Griffin; Ralph P Mason Journal: Cancer Res Date: 2020-12-01 Impact factor: 13.312
Authors: Niloufar Zarghami; Donna H Murrell; Michael D Jensen; Frederick A Dick; Ann F Chambers; Paula J Foster; Eugene Wong Journal: Radiat Oncol Date: 2018-06-01 Impact factor: 3.481
Authors: Niloufar Zarghami; Alexandre A Khrapitchev; Francisco Perez-Balderas; Manuel Sarmiento Soto; James R Larkin; Luca Bau; Nicola R Sibson Journal: Int J Nanomedicine Date: 2018-07-25