文档介绍：MUNICATIONS
Perivascular nitric oxide gradients laser-scanning microscopy (MPLSM) (Supplementary Methods
online). DAF-2–associated fluorescence was observed in both the
normalize tumor vasculature vascular region and the parenchyma of control U87MG tumors
(Fig. 1a), whereas it was abolished by treatment with a pan-NOS
1 1 1 1
Satoshi Kashiwagi , Kosuke Tsukada , Lei Xu , Junichi Miyazaki , inhibitor, L-NMMA (Supplementary Fig. 2a online). In contrast,
Sergey V Kozin1, James A Tyrrell1, William C Sessa2, DAF-2–associated fluorescence predominantly localized to blood
Leo E Gerweck1, Rakesh K Jain1 & Dai Fukumura1 vessels in NOS1-silenced U87MG tumors, indicating perivascular
gradients of NO (Fig. 1a).
Normalization of tumor vasculature is an emerging strategy to We then determined the alteration of tumor vascular morphology
improve cytotoxic therapies. Here we show that eliminating and function caused by the establishment of perivascular NO gradients.
nitric oxide (NO) production from tumor cells via neuronal Blood vessels were more evenly distributed and less tortuous in NOS1-
NO synthase silencing or inhibition establishes perivascular silenced tumors as determined by intravital MPLSM (Fig. 1b). Notably,
gradients of NO in human glioma xenografts in mice and silencing of NOS1 in the glioma cells significantly increased vessel
normalizes the tumor vasc