Effects of aromatase inhibitors on the pathobiology of the human breast, endometrial and ovarian carcinoma
| Autor: | William R. Miller, Hironobu Sasano, Thomas J. Anderson, J Nakamura, Kiyoshi Ito, M Yoshihama, K Ariga, Akira Yajima, S Sato |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
medicine.medical_specialty Neoplasms Hormone-Dependent medicine.drug_class Endocrinology Diabetes and Metabolism Estrogen receptor Antineoplastic Agents Apoptosis Breast Neoplasms Aromatase Endocrinology Breast cancer Internal medicine Ovarian carcinoma medicine Humans Enzyme Inhibitors Ovarian Neoplasms Aromatase inhibitor biology Aromatase Inhibitors business.industry Endometrial cancer medicine.disease Immunohistochemistry Endometrial Neoplasms Ki-67 Antigen Receptors Estrogen Oncology Estrogen biology.protein Female Ovarian cancer business Cell Division |
| Zdroj: | Endocrine-related cancer. :197-204 |
| ISSN: | 1351-0088 |
| DOI: | 10.1677/erc.0.0060197 |
| Popis: | It is very important to examine the influence of inhibition of in situ estrogen production on the pathobiology of human sex steroid-dependent tumors in order to understand the clinical effects of aromatase inhibitors. We have examined the biological changes before and after aromatase inhibitor treatment in vitro (endometrial and ovarian cancer) and in vivo (breast cancer). First, we analyzed these changes using histoculture of 15 human endometrial cancers and 9 ovarian cancers. Five of the fifteen endometrial cancers and four of the nine ovarian cancers demonstrated decreased [3H]thymidine uptake or Ki67 labeling index after 14alpha-hydroxy-4-androstene-3,6,17-trione (NKS01) treatment. In ovarian cancer cases, the responsive cases tended to be associated with higher aromatase and estrogen receptor alpha (ER) expression compared with the other cases but this was not seen in the endometrial cancer cases. There were no changes in ER and aromatase expression before and after NKS01 treatment in either ovarian or endometrial cancer cases. We then studied the same primary human breast tumors before and after aminoglutethimide (AMG, n=3) and 4-hydroxyandrostenedione (4-OHA, n=3) treatment. Tumor aromatase activity increased in 3 cases and decreased or was unchanged in 3 cases but aromatase immunoreactivity in stroma and adipocytes was unaltered in 5 cases. There were no changes in the ER labeling index before or after treatment. Five of the six cases including the responsive cases tended to be associated with decreased cell proliferation or Ki67 expression and increased apoptosis when examined by the TUNEL method. These results indicate that aromatase inhibitors may exert their effects on human breast and other cancers through decreasing proliferation and increasing apoptosis, possibly without altering ER status. |
| Databáze: | OpenAIRE |
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