Reference : Botulinum toxin potentiates cancer radiotherapy and chemotherapy
Scientific journals : Article
Human health sciences : Radiology, nuclear medicine & imaging
Human health sciences : Oncology
http://hdl.handle.net/2268/73977
Botulinum toxin potentiates cancer radiotherapy and chemotherapy
English
[fr] La toxine botulique potentialise la radiothérapie du cancer et la chimiothérapie.
ANSIAUX, Reginald [Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance > > >]
BAUDELET, Christine [Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance; > > >]
CRON, Greg [Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance > > >]
SEGERS, Jerome [Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance;Laboratory of Medicinal Chemistry and Radiopharmacy > > >]
DESSY, Chantal [Université Catholique de Louvain - UCL > Laboratory of Pharmacology and Therapeutics > > >]
Martinive, Philippe mailto [Université Catholique de Louvain - UCL > > Laboratory of Pharmacology and Therapeutics > >]
DE WEVER, Julie [Université Catholique de Louvain - UCL > Laboratory of Pharmacology and Therapeutics > > >]
VERRAX, Julien [Université Catholique de Louvain - UCL > Metabolism, Nutrition and Toxicology Unit > Pharmacokinetic, > >]
WAUTHIER, Valérie [Université Catholique de Louvain - UCL > Nutrition and Toxicology Unit > Metabolism, > >]
BEGHEIN, Nelson [Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance; Laboratory of Medicinal Chemistry and Radiopharmacy > > >]
GREGOIRE, Vincent [Université Catholique de Louvain - UCL > Metabolism, Nutrition and Toxicology Unit > Pharmacokinetic, > >]
BUC CALDERON, Pedro [Université Catholique de Louvain - UCL > Pharmacokinetic, > Metabolism, Nutrition and Toxicology Unit > >]
FERON, Olivier [Université Catholique de Louvain - UCL > Laboratory of Pharmacology and Therapeutics > > >]
GALLEZ, Bernard [Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance; Laboratory of Medicinal Chemistry and Radiopharmacy > > >]
15-Feb-2006
Clinical Cancer Research : An Official Journal of the American Association for Cancer Research
American Association for Cancer Research, Inc. (AACR)
12
4
1276/83
Yes (verified by ORBi)
International
1078-0432
Birmingham
AL
[en] Enzyme ; Enzyme ; Hydrolases ; Peptidases ; Metalloendopeptidases ; Chemotherapy ; Treatment ; Radiotherapy ; Malignant tumor ; Bontoxilysin ; ; Bontoxilysin ; Malignant tumor ; Radiotherapy ; Treatment ; Chemotherapy ; Metalloendopeptidases ; Peptidases ; Hydrolases
[fr] Enzyme ; Bontoxilysin ; Tumeur maligne ; Radiothérapie ; Traitement ; Chimiothérapie ; Metalloendopeptidases ; Peptidases ; Hydrolases
[fr] OBJECTIF: Des anomalies structurales et fonctionnelles dans le réseau vasculaire tumoral sont considérés comme des facteurs de résistance des tumeurs solides et à des traitements cytotoxiques. 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. Pour augmenter l'efficacité des traitements anticancéreux, les efforts doivent être déployés pour trouver de nouvelles stratégies pour l'ouverture transitoire de la tumeur vasculaire à atténuer l'hypoxie tumorale (source de résistance à la radiothérapie) et améliorer la prestation des agents chimiothérapeutiques. 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. Nous avons supposé que neurotoxine botulique de type A (BoNT-A) pourrait interférer avec la libération des neurotransmetteurs à la bienveillance varicosités périvasculaire, conduisant à une inhibition des contractions neurogène des vaisseaux de la tumeur et donc d'améliorer la perfusion et l'oxygénation tumorale.
<br />
<br />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. CONCEPTION EXPERIMENTALE: Pour tester cette hypothèse, la BoNT-A ont été injectés localement dans les tumeurs de souris (fibrosarcome FSaII, tumeur du foie hépatocarcinome transplantable), et la résonance paramagnétique électronique oxymétrie a été utilisé pour surveiller pO (2) in vivo de façon répétée pendant 4 jours. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. En outre, de contraste d'imagerie par résonance magnétique a été utilisée pour mesurer la perfusion tumorale 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. Enfin, les artères isolées ont été montés dans myographe fil pour suivre spécifiquement le ton neurogène développée par artérioles qui ont été cooptés par la croissance des cellules tumorales environnantes.
<br />
<br />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). RÉSULTATS: L'utilisation de ces modèles de tumeurs, nous avons montré que l'administration locale de la BoNT-A (deux sites; dose, 29 unités / kg) augmente considérablement l'oxygénation tumorale et de la perfusion, conduisant à une amélioration substantielle de la réponse tumorale à la radiothérapie (20 Gy de 250 kV rayonnement) et la chimiothérapie (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. Cette thérapeutique résultats gain observé à partir d'une ouverture de la tumeur vasculaire par BoNT-A, car nous avons montré que la BoNT-A pourrait empêcher ton neurogène dans la vascularisation des tumeurs.
<br />
<br />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. CONCLUSIONS: L'ouverture du lit vasculaire induite par la BoNT-A offre un moyen d'augmenter significativement la réponse des tumeurs à la radiothérapie et la chimiothérapie.
[en] 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.
<br />
<br />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.
<br />
<br />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.
<br />
<br />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.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/73977

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