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Acknowledgements The authors thank members of their lab for support and reading of various sections of this Review, and their funders the Wellcome Trust, the Medical Research Council and The Scar Free Foundation

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Shklar and coworkers (173) examined the effects of methotrexate on hamster buccal pouch carcinomas generated by 9,10-dimethyl-l,2-benzanthracene and found that the methotrexate-treated group reported tumors that were larger and more anaplastic and that they progressed more quickly than the control group

However, the magnitude of VEGF change and the upstream signaling pathway driving it are not established with the precision needed to predict dose-response in humans