title: The effect of chemotherapeutic agents on tumor vasculature in subcutaneous and orthotopic human tumor xenografts.
abstract: BACKGROUND
  The growth of solid tumors and their regrowth after treatment is dependent upon functional tumor vasculature. Some chemotherapeutic agents have shown anti-angiogenic properties but there are limited studies of the effect of chemotherapy on tumor vasculature. Here we investigate the effect of paclitaxel, 5-fluorouracil (5-FU) and doxorubicin on tumor vasculature in subcutaneous and orthotopic xenografts in mice.
  
  
  METHODS
  The vascular density and percentage of functional blood vessels were evaluated in subcutaneous A431 human vulvar cancer xenografts, and in subcutaneous and orthotopic MCF-7 human breast cancer xenografts, following single doses of paclitaxel, 5-FU or doxorubicin.
  
  
  RESULTS
  There was no significant difference in total (CD31+) blood vessels between untreated ectopic and orthotopic MCF-7 tumors, but there was a significantly lower proportion of functional blood vessels in orthotopic tumors. After paclitaxel treatment, there was a decrease in functional tumor vasculature in A431 subcutaneous xenografts, followed by a subsequent rebound. There was a significant decrease in total vascular density on day 12 in A431 tumors following 5-FU or doxorubicin treatment, but no change in the percentage of functional vessels. An increase in functional blood vessels or percentage of functional vasculature was noted in MCF-7 subcutaneous and orthotopic xenografts following chemotherapy treatment.
  
  
  CONCLUSIONS
  There are differences in the vasculature and microenvironment of ectopic and orthotopic xenografts in mice. Anti-tumor effects of chemotherapy may be due, in part, to effects on tumor vasculature and may vary in different tumor models.
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, 610 University Avenue, Toronto, ON, M5G 2 M9, Canada. asfung@ucalgary.ca.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Fung
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, 610 University Avenue, Toronto, ON, M5G 2 M9, Canada. carol.lee@sickkids.ca.
authors.forename: Carol
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, 610 University Avenue, Toronto, ON, M5G 2 M9, Canada. man.yu@sickkids.ca.
authors.forename: Man
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, 610 University Avenue, Toronto, ON, M5G 2 M9, Canada. ian.tannock@uhn.ca.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers