Hamade Diala F, Epperly Michael W, Fisher Renee, Hou Wen, Shields Donna, van Pijkeren Jan-Peter, Mukherjee Amitava, Yu Jian, Leibowitz Brian J, Vlad Anda M, Coffman Lan, Wang Hong, Huq M Saiful, Huang Ziyu, Rogers Claude J, Greenberger Joel S
Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
Department of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USA.
Cancers (Basel). 2023 Mar 8;15(6):1670. doi: 10.3390/cancers15061670.
Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Thus, strategies to mitigate toxicity are important and can revitalize the current standard of care. We previously established that LR-IL-22 protects the intestine from WAI. We now hypothesize that LR-IFN-β is an effective radiation protector and mitigator and is rapidly cleared from the digestive tract, making it an option for intestinal radioprotection. We report that the gavage of LR-IFN-β during WAI provides improved intestinal barrier integrity and significantly preserves the numbers of Lgr5+GFP+ intestinal stem cells, improving survival. The rapid clearance of the genetically engineered probiotic from the digestive tract renders it a safe and feasible radiation mitigator. Therefore, the above genetically engineered probiotic is both a feasible and effective radiation mitigator that could potentially revolutionize the management of OC patients. Furthermore, the subsequent addition of platinum/taxane-based chemotherapy to the combination of WAI and LR-IFN-β should reduce tumor volume while protecting the intestine and should improve the overall survival in OC patients.
放疗可以是卵巢癌的一种有效治疗方法,但其应用受到肠道毒性的限制。因此,减轻毒性的策略很重要,并且可以振兴当前的护理标准。我们之前已经确定LR-IL-22可保护肠道免受腹部照射损伤。我们现在假设LR-IFN-β是一种有效的辐射防护剂和减轻剂,并且能从消化道快速清除,使其成为肠道辐射防护的一个选择。我们报告称,在腹部照射损伤期间灌胃LR-IFN-β可改善肠道屏障完整性,并显著保留Lgr5+GFP+肠道干细胞数量,从而提高生存率。这种基因工程益生菌从消化道的快速清除使其成为一种安全可行的辐射减轻剂。因此,上述基因工程益生菌既是一种可行且有效的辐射减轻剂,有可能彻底改变卵巢癌患者的治疗方式。此外,在腹部照射损伤和LR-IFN-β联合治疗的基础上随后添加铂类/紫杉烷类化疗应能在保护肠道的同时缩小肿瘤体积,并应能提高卵巢癌患者的总生存率。