Publication Date:
2003-05-17
Description:
About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia-Barros, Monica -- Paris, Francois -- Cordon-Cardo, Carlos -- Lyden, David -- Rafii, Shahin -- Haimovitz-Friedman, Adriana -- Fuks, Zvi -- Kolesnick, Richard -- CA 52462/CA/NCI NIH HHS/ -- CA 85704/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 May 16;300(5622):1155-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12750523" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Apoptosis
;
Bone Marrow Transplantation
;
Disease Models, Animal
;
Endothelium, Vascular/enzymology/*pathology
;
Fibrosarcoma/blood supply/*radiotherapy
;
In Situ Nick-End Labeling
;
Melanoma, Experimental/blood supply/*radiotherapy
;
Mice
;
Neoplasm Transplantation
;
Neovascularization, Pathologic
;
Proto-Oncogene Proteins/genetics
;
*Proto-Oncogene Proteins c-bcl-2
;
Radiation Tolerance
;
Sphingomyelin Phosphodiesterase/genetics
;
bcl-2-Associated X Protein
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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