Dynamics of tumor oxygenation, CD31 staining and transforming growth factor-β levels after treatment with radiation or cyclophosphamide in the rat 13762 mammary carcinoma

Yoshihiro Kakeji, Yoshihiko Maehara, Masahiko Ikebe, Beverly A. Teicher

研究成果: Contribution to journalArticle査読

48 被引用数 (Scopus)

抄録

Purpose: Tumors are dynamic tissues that undergo marked molecular, biochemical, and physiologic changes in response to cytotoxic anticancer therapies. Understanding the changes in tumor oxygenation and transforming growth factor-β expression may allow improved treatment regimens to be developed. Methods and Materials: The effects of a single dose of radiation therapy (20 Gy) or a single dose of chemotherapy (cyclophosphamide, 250 mg/kg) on several molecular and physiologic parameters of the rat 13762 mammary carcinoma growing subcutaneously in female Fischer 344 rats were explored. Results: Treatment of the tumor-bearing animals with 20 Gy of radiation killed about two logs (99%) of the 13762 tumor cells, and treatment with cyclophosphamide (250 mg/kg) killed about 1.5 logs (95%) of the 13762 tumor cells. Hypoxia, as determined by a pO2 electrode, initially decreased in the tumors of treated animals until 6 h. posttreatment and then increased, so that 24 h. after administration of the radiation therapy or the chemotherapy the number of intratumoral vessels as determined by CD31 staining increased until about 24 h after cytotoxic therapy. Transforming growth factor-β1, measured by radioimmunoassay, peaked in the serum between 6 h and 18 h and again between 72 h and 96 h after radiation therapy and peaked in the tumor at 24 h and again at 72 h after radiation therapy. The first serum peak after cyclophosphamide was 3 h after drug injection, with second peaks at 36 h and 48 h after drug administration. In the tumor, transforming growth factor-β1 peaked between 6 h and 8 h after drug administration and again 36 h and 72 h after drug. Apoptosis was maximal 6 h after 20 Gy and 24 h after cyclophosphamide. Vascular endothelial growth factor was also increased in tumors after cytotoxic therapy. Conclusions: These changes in the tumor physiologic status are sufficient to protect the tumor from a second cytotoxic insult administered days afterwards and to result in a restructuring of the tissue.

本文言語英語
ページ(範囲)1115-1123
ページ数9
ジャーナルInternational Journal of Radiation Oncology Biology Physics
37
5
DOI
出版ステータス出版済み - 3 15 1997

All Science Journal Classification (ASJC) codes

  • 放射線
  • 腫瘍学
  • 放射線学、核医学およびイメージング
  • 癌研究

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