Koonce Nathan A, Juratli Mazen A, Cai Chengzhong, Sarimollaoglu Mustafa, Menyaev Yulian A, Dent Judith, Quick Charles M, Dings Ruud P M, Nedosekin Dmitry, Zharov Vladimir, Griffin Robert J
University of Arkansas for Medical Sciences, Department of Radiation Oncology, Little Rock, AR, USA; National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA.
University of Arkansas for Medical Sciences, Arkansas Nanomedicine Center, Little Rock, AR, USA; Frankfurt University Hospitals, Goethe-University Frankfurt/Main, Department of General and Visceral Surgery, Frankfurt/Main, Germany.
Biochem Biophys Res Commun. 2017 Oct 21;492(3):507-512. doi: 10.1016/j.bbrc.2017.08.053. Epub 2017 Aug 16.
Noninvasive biological readouts of tumor metastatic risk and therapeutic efficacy are needed as healthcare costs rise. CTCs are the source of metastasis in distant organs that are responsible for the majority of cancer-related deaths. Here we demonstrate the acute and long-term effect of vascular disrupting therapies (high-dose radiotherapy and tumor necrosis factor-alpha (TNF)) on CTCs released from the primary tumor with a non-invasive real-time in vivo flow cytometry system. Using our innovative flow cytometry platform, we show here that radiation and nanodrug treatment can lead to short term release of CTC from the primary tumor. There was no increase in metastasis frequency or extent between control and TNF-treated mice; however, a significant reduction in lung metastasis was noted in the radiotherapy alone group. Mice treated with both TNF and radiotherapy had a slightly elevated metastatic profile between that of radiation alone and control (untreated) tumors. Possible mechanisms based on therapy specific vessel disruption and cell death are discussed. Overall, CTCs correlated with tumor progression and suggest CTC enumeration described herein may be useful in clinical management of solid tumor malignancies.
随着医疗成本的上升，需要肿瘤转移风险和治疗效果的非侵入性生物学读数。循环肿瘤细胞（CTCs）是远处器官转移的来源，而远处器官转移是大多数癌症相关死亡的原因。在此，我们使用非侵入性实时体内流式细胞术系统，证明了血管破坏疗法（高剂量放疗和肿瘤坏死因子-α（TNF））对原发肿瘤释放的CTCs的急性和长期影响。使用我们创新的流式细胞术平台，我们在此表明，放疗和纳米药物治疗可导致原发肿瘤短期释放CTCs。在对照小鼠和TNF治疗的小鼠之间，转移频率或转移范围没有增加；然而，仅放疗组的肺转移明显减少。同时接受TNF和放疗治疗的小鼠的转移情况略高于单纯放疗组和对照（未治疗）肿瘤组。讨论了基于治疗特异性血管破坏和细胞死亡的可能机制。总体而言，CTCs与肿瘤进展相关，并且表明本文所述的CTCs计数可能对实体瘤恶性肿瘤患者的临床管理有用。
