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Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

[ Vol. 14 , Issue. 21 ]

Author(s):

M. P. Bernard, S. Bancos, P. J. Sime and R. P. Phipps   Pages 2051 - 2060 ( 10 )

Abstract:


There is much interest in the potential use of Cox-2 selective inhibitors in combination with other cancer therapeutics. Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase- 2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkins lymphoma, non-Hodgkins lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastasis. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies.

Keywords:

cyclooxygenase-2 (Cox-2),inflammation,hematological malignancies,chronic lymphocytic,leukemia,chronic myeloid leukemia,Hodgkin's lymphoma,multiple myeloma,anti-tumor immunity,angiogenesis

Affiliation:

, , , Box 850, MRBX 3-11001,Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642,USA.



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