Publication Date:
2002-02-23
Description:
The p53 tumor suppressor gene is inactivated in the majority of human cancers. Tumor cells deficient in p53 display a diminished rate of apoptosis under hypoxic conditions, a circumstance that might reduce their reliance on vascular supply, and hence their responsiveness to antiangiogenic therapy. Here, we report that mice bearing tumors derived from p53(-/-) HCT116 human colorectal cancer cells were less responsive to antiangiogenic combination therapy than mice bearing isogenic p53(+/+) tumors. Thus, although antiangiogenic therapy targets genetically stable endothelial cells in the tumor vasculature, genetic alterations that decrease the vascular dependence of tumor cells can influence the therapeutic response of tumors to this therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Joanne L -- Rak, Janusz W -- Coomber, Brenda L -- Hicklin, Daniel J -- Kerbel, Robert S -- CA-41233/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 22;295(5559):1526-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sunnybrook and Women's College Health Sciences Centre, Molecular and Cellular Biology Research, Room S-218, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11859195" target="_blank"〉PubMed〈/a〉
Keywords:
Angiogenesis Inhibitors/pharmacology/*therapeutic use
;
Animals
;
Antibodies/therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use
;
Apoptosis
;
*Cell Hypoxia
;
Cell Survival
;
Colorectal Neoplasms
;
Cyclin-Dependent Kinase Inhibitor p21
;
Cyclins/genetics/metabolism
;
Gene Deletion
;
*Gene Silencing
;
*Genes, p53
;
Humans
;
In Situ Nick-End Labeling
;
Mice
;
Mice, SCID
;
Neoplasm Transplantation
;
Neoplasms, Experimental/blood supply/*drug therapy/*genetics/pathology
;
Receptor Protein-Tyrosine Kinases/immunology
;
Receptors, Growth Factor/immunology
;
Receptors, Vascular Endothelial Growth Factor
;
Tumor Cells, Cultured
;
Tumor Suppressor Protein p53/metabolism
;
Vinblastine/therapeutic use
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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