Anti-vascular effects of vinflunine in the MAC 15A transplantable adenocarcinoma model

Anti-vascular effects of the novel Vinca alkaloid, vinflunine have been investigated in the MAC 15A transplantable murine colon adenocarcinoma model and compared with those induced by the most recently identified clinically useful third generation Vinca . Administration of the maximum tolerated dose...

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Bibliographic Details
Published in:British journal of cancer 2001, Vol.84 (2), p.290-295
Main Authors: Holwell, S E, Hill, B T, Bibby, M C
Format: Article
Language:English
Subjects:
Adenocarcinoma - pathology
Adenocarcinoma - prevention & control
Angiogenesis Inhibitors - pharmacology
Animals
Antineoplastic agents
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cancer therapies
Chemotherapy
Cocoa
Disease Models, Animal
Dose-Response Relationship, Drug
Drug dosages
Drug Resistance
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Epidemiology
Humans
Male
Medical research
Medical sciences
Mice
Mice, Inbred Strains
Molecular Medicine
Neoplasm Transplantation
Neoplasms, Experimental - pathology
Neoplasms, Experimental - prevention & control
Neovascularization, Pathologic - prevention & control
Oncology
Pharmacology. Drug treatments
Regular
regular-article
Time Factors
Tumor Cells, Cultured
Tumors
Umbilical Veins
Vinblastine - analogs & derivatives
Vinblastine - pharmacology
Vincristine - pharmacology
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Summary:Anti-vascular effects of the novel Vinca alkaloid, vinflunine have been investigated in the MAC 15A transplantable murine colon adenocarcinoma model and compared with those induced by the most recently identified clinically useful third generation Vinca . Administration of the maximum tolerated dose of either vinflunine (50 mg kg –1 ) or vinorelbine (8 mg kg –1 ) resulted in significant tumour growth delay with subsequent histological analysis revealing substantial haemorrhagic necrosis. This suggested possible anti-vascular effects and these were confirmed by Hoechst 33342 perfusion studies. Vinflunine, currently undergoing Phase I trials in Europe, was found to be at least as effective as the clinically active vincristine and vinorelbine in this model and, remarkably, produced anti-vascular effects at doses much lower than the maximum tolerated dose. Although vinflunine caused apoptosis in HUVEC monolayer cultures this event did not occur within the first 8 hours of exposure whereas vascular shutdown in vivo was observed within the first 4 hours. © 2001 Cancer Research Campaign http://www.bjcancer.com
ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1054/bjoc.2000.1587