Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
Department of DLAR-Veterinary Services, University of Pittsburgh, Pittsburgh, PA, U.S.A.
In Vivo. 2024 Nov-Dec;38(6):2582-2590. doi: 10.21873/invivo.13734.
BACKGROUND/AIM: Radiation oncologists are reluctant to treat cancer in Fanconi Anemia (FA) patients due to their lack of homologous recombination repair of DNA strand breaks in normal tissues. To determine the therapeutic effects of irradiation and combination chemotherapy on cancer in syngeneic, radiosensitive FA mice, we derived transplantable cancers of the same genotype in three FA mouse strains.
Fancd2-/- mice on a C57BL/6 or Sv/129 background and Fancg-/- mice (C57BL/6 background) that received 3-methylcholanthrene (3-MCA), were monitored for the development of subcutaneous tumors.
Tumors were induced at the site of 3-MCA injection, and tumor cell lines were established and found to be transplantable. Explanted tumors were identified as pleomorphic/rhabdomyosarcomas using immunohistochemical biomarkers.
These transplantable FA mouse tumor cell lines should be valuable for testing effects of new radiation therapy protocols including FLASH high dose rate radiation delivery, immunotherapies, and combined radiation and chemotherapy treatments for radiosensitive FA patients.
背景/目的：由于缺乏正常组织中 DNA 链断裂的同源重组修复，放射肿瘤学家不愿意治疗范可尼贫血（FA）患者的癌症。为了确定照射和联合化疗对同基因、辐射敏感 FA 小鼠癌症的治疗效果，我们在三种 FA 小鼠品系中衍生出了可移植的同种癌症。
在 C57BL/6 或 Sv/129 背景下的 Fancd2-/- 小鼠和接受 3-甲基胆蒽（3-MCA）的 Fancg-/- 小鼠（C57BL/6 背景）中，监测皮下肿瘤的发展情况。
在 3-MCA 注射部位诱导出肿瘤，建立并发现可移植的肿瘤细胞系。通过免疫组织化学生物标志物鉴定，移植的肿瘤被鉴定为多形性/横纹肌肉瘤。
这些可移植的 FA 小鼠肿瘤细胞系对于测试新的放射治疗方案的效果应该是有价值的，包括 FLASH 高剂量率放射治疗、免疫疗法以及对辐射敏感的 FA 患者的联合放射和化疗治疗。
