Botulinum toxin potentiates cancer radiotherapy and chemotherapy.

@article{citeulike:2058303, abstract = {PURPOSE: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation. EXPERIMENTAL DESIGN: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO(2) in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells. RESULTS: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature. CONCLUSIONS: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy.}, address = {Laboratory of Biomedical Magnetic Resonance, Universit\'{e} Catholique de Louvain, Brussels, Belgium.}, author = {Ansiaux, R. and Baudelet, C. and Cron, G. O. and Segers, J. and Dessy, C. and Martinive, P. and De Wever, J. and Verrax, J. and Wauthier, V. and Beghein, N. and Gr\'{e}goire, V. and Buc Calderon, P. and Feron, O. and Gallez, B. }, citeulike-article-id = {2058303}, doi = {http://dx.doi.org/10.1158/1078-0432.CCR-05-1222}, issn = {1078-0432}, journal = {Clin Cancer Res}, keywords = {pubmed, tool}, month = {February}, number = {4}, pages = {1276--1283}, posted-at = {2007-12-04 23:56:35}, priority = {2}, title = {Botulinum toxin potentiates cancer radiotherapy and chemotherapy.}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-05-1222}, volume = {12}, year = {2006} }

TY - JOUR ID - citeulike:2058303 L3 - citeulike-article-id:2058303 TI - Botulinum toxin potentiates cancer radiotherapy and chemotherapy. JF - Clin Cancer Res VL - 12 IS - 4 SP - 1276 EP - 1283 AD - Laboratory of Biomedical Magnetic Resonance, Université Catholique de Louvain, Brussels, Belgium. SN - 1078-0432 N2 - PURPOSE: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation. EXPERIMENTAL DESIGN: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO(2) in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells. RESULTS: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature. CONCLUSIONS: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy. KW - pubmed KW - tool AU - Ansiaux, R AU - Baudelet, C AU - Cron, GO AU - Segers, J AU - Dessy, C AU - Martinive, P AU - De Wever, J AU - Verrax, J AU - Wauthier, V AU - Beghein, N AU - Grégoire, V AU - Buc Calderon, P AU - Feron, O AU - Gallez, B PY - 2006/02/15/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-05-1222 ER -