Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
Cancer Lett. 2011 Dec 8;311(2):219-29. doi: 10.1016/j.canlet.2011.07.023. Epub 2011 Aug 6.
The goal of this study is to determine whether treatment with methylselenocysteine (MSC) results in differential uptake of irinotecan and its active metabolite (SN-38) between tumors of head and neck squamous cell carcinomas and normal tissue. The in vivo synergy between MSC and irinotecan is influenced by treatment schedule and associated with enhancement of tumor vessel maturation, intra-tumor concentration of SN-38 and apoptotic death of tumor cells. Normal tissue drug concentrations were not impacted by selenium treatment. The finding is of clinical relevance for enabling the delivery of higher doses of irinotecan to reverse tumor resistance, recurrence and ultimately enhancing cure rates.
本研究旨在确定甲基硒代半胱氨酸 (MSC) 的治疗是否会导致头颈部鳞状细胞癌肿瘤和正常组织之间伊立替康及其活性代谢物 (SN-38) 的摄取存在差异。MSC 和伊立替康的体内协同作用受治疗方案的影响,并与增强肿瘤血管成熟、SN-38 在肿瘤内的浓度和肿瘤细胞的凋亡死亡有关。硒处理不会影响正常组织的药物浓度。这一发现对临床具有重要意义,因为它可以使更高剂量的伊立替康用于逆转肿瘤耐药、复发,并最终提高治愈率。