Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles

Frontiers in Oncology

Oncology

Bohdan J. Soltys¹  Carleton J. C. Hsia¹  Katie B. Grausam²  Shanta M. Messerli²  Haotian Zhao³ 

[1] AntiRadical Therapeutics LLC, Sioux Falls, SD, United States;Cancer Biology and Immunotherapies, Sanford Research, Sioux Falls, SD, United States;Cancer Biology and Immunotherapies, Sanford Research, Sioux Falls, SD, United States;Department of Pediatrics, University of South Dakota, Vermillion, SD, United States;Department of Biomedical Sciences, New York Institute of Technology, Old Westbury, NY, United States;

关键词: Sonic Hedgehog;    medulloblastoma;    metastasis;    leptomeningeal dissemination;    hematogenous dissemination;    nitroxide;    reactive oxygen species;    reactive nitrogen species;   

DOI  :  10.3389/fonc.2023.1129533

 received in 2023-01-03, accepted in 2023-04-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

Medulloblastoma is a tumor of the cerebellum that metastasizes to the leptomeninges of the central nervous system (CNS), including to forebrain and to spinal cord. The inhibitory effect of polynitroxylated albumin (PNA), a caged nitroxide nanoparticle, on leptomeningeal dissemination and metastatic tumor growth was studied in a Sonic Hedgehog transgenic mouse model. PNA treated mice showed an increased lifespan with a mean survival of 95 days (n = 6, P<0.05) compared with 71 days in controls. In primary tumors, proliferation was significantly reduced and differentiation was significantly increased (P<0.001) as shown by Ki-67+ and NeuN+ immunohistochemistry, while cells in spinal cord tumors appeared unaffected. Yet, histochemical analysis of metastatic tumor in spinal cord showed that the mean total number of cells in spinal cord was significantly reduced in mice treated with PNA compared to albumin vehicle (P<0.05). Examination of various levels of the spinal cord showed that PNA treated mice had significantly reduced metastatic cell density in the thoracic, lumbar and sacral spinal cord levels (P<0.05), while cell density in the cervical region was not significantly changed. The mechanism by which PNA may exert these effects on CNS tumors is discussed.

【 授权许可】

Unknown   
Copyright © 2023 Soltys, Grausam, Messerli, Hsia and Zhao