在原位小鼠胰腺癌模型中，通过加压区域血管内给药可将奥沙利铂诱导的周围神经病变降至最低。
Oxaliplatin-induced peripheral neuropathy can be minimized by pressurized regional intravascular delivery in an orthotopic murine pancreatic cancer model.
作者信息
Shankara Narayanan Jayanth Surya Narayanan, Frizzi Katie, Erdem Suna, Ray Partha, Jaroch David, Cox Bryan, Katz Steven, Vicente Diego, White Rebekah
机构信息
Moores Cancer Center, University of California, 3855 Health Sciences Dr, Rm 2336, La Jolla, San Diego, CA, 92037, USA.
Department of Pathology, University of California, San Diego, CA, USA.
出版信息
Discov Oncol. 2022 Apr 6;13(1):21. doi: 10.1007/s12672-022-00483-4.
PURPOSE
There is a great need to reduce the toxicity of chemotherapy used in the management of pancreatic ductal adenocarcinoma (PDAC). Here we explore if regional pressurized delivery of oxaliplatin can minimize peripheral neuropathy in mice.
METHODS
We used an orthotopic PDAC mouse model and delivered a single dose of oxaliplatin through the portal vein using a pressure-enabled system (pancreatic retrograde venous infusion, PRVI). We analyzed the effects of PRVI on tumor burden and peripheral neuropathy using histopathological and functional assays.
RESULTS
Tumor weights in mice treated with 2 mg/kg oxaliplatin using PRVI were significantly lower than in mice treated with the same dose systemically. This resulted in reduced peripheral neuropathy signatures in PRVI mice compared to the 20 mg/kg systemic dose required to achieve similar tumor control.
CONCLUSION
Regional delivery of highly cytotoxic agents using PRVI can reduce the therapeutic dose of these drugs, thereby lowering toxic side effects.
目的
在胰腺导管腺癌（PDAC）的治疗中，非常需要降低化疗药物的毒性。在此，我们探讨通过区域加压给药奥沙利铂是否可以使小鼠的周围神经病变降至最低。
方法
我们使用了原位PDAC小鼠模型，并通过压力驱动系统（胰腺逆行静脉输注，PRVI）经门静脉给予单剂量奥沙利铂。我们使用组织病理学和功能分析方法分析了PRVI对肿瘤负荷和周围神经病变的影响。
结果
使用PRVI给予2mg/kg奥沙利铂治疗的小鼠的肿瘤重量显著低于全身给予相同剂量的小鼠。与达到相似肿瘤控制所需的20mg/kg全身剂量相比，这导致PRVI小鼠的周围神经病变特征减少。
结论
使用PRVI进行高细胞毒性药物的区域给药可以降低这些药物的治疗剂量，从而降低毒副作用。
Zotero 插件