Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis
Autor: | Shahin Rafii, Adriana Haimovitz-Friedman, Richard Kolesnick, David Lyden, François Paris, Carlos Cordon-Cardo, Zvi Fuks, Monica Garcia-Barros |
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Rok vydání: | 2003 |
Předmět: |
Endothelium
Fibrosarcoma medicine.medical_treatment Melanoma Experimental Apoptosis Radiation Tolerance Mice Bcl-2-associated X protein Proto-Oncogene Proteins In Situ Nick-End Labeling medicine Animals Bone Marrow Transplantation bcl-2-Associated X Protein Multidisciplinary Neovascularization Pathologic biology Melanoma Growth factor Cancer medicine.disease Endothelial stem cell Radiation therapy Disease Models Animal Sphingomyelin Phosphodiesterase medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Immunology Cancer research biology.protein Endothelium Vascular Neoplasm Transplantation |
Zdroj: | Science. 300:1155-1159 |
ISSN: | 1095-9203 0036-8075 |
Popis: | 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. |
Databáze: | OpenAIRE |
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