RESUMO
Several biological and clinical considerations suggest the involvement of cyclooxygenase-2 (COX-2), the key enzyme of prostaglandin (PG) synthesis, in the pathogenesis and progression of haematological malignancies. Despite the wealth of data concerning COX-2 expression, only limited information is available on multiple myeloma (MM). Using standard immunohistochemistry we therefore evaluated COX-2 protein expression in samples from 57 patients with a primary diagnosis of MM. Time to progression and a variety of clinicopathological features were evaluated by the Kaplan-Meier method and the Cox regression model. In addition, COX-2 expression was evaluated by staining bone marrow from healthy donors and 11 patients with MGUS. Overall, 31 MM samples (54%) expressed COX-2. Positivity for COX-2 was unrelated to stage or clinical or molecular features of the disease. However, patients with COX-2 positive tumours experienced a significantly shorter time to progression (17 vs 30 months, p = 0.037). In summary, COX-2 is frequently expressed in MM and correlates with shorter progression-free survival.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Mieloma Múltiplo/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
OBJECTIVE: The influence of the mimic hematopoietic microenvironment and adhesion factor on the initial divisional behavior of human cord blood hematopoietic progenitors was studied in the culture system with certain cytokines. METHODS: (1) CD(34)(+) CD(38)(-) single cell was sorted by FACS. (2) The stem cell supporting stromal feeder layer AFT024 and single adhesive factor fibronectin (Fn) were used in the culture system and their influence on the initial division was observed. RESULTS: (1) In the presence of the combined cytokines, the CD(34)(+) CD(38)(-) human cord blood cells displayed fixed fraction of quiescent, slow and fast division, and asymmetric division. (2) There was no influence of adhesive factor itself on initial division of CD(34)(+) CD(38)(-) cells. (3) The hematopoietic microenvironment mimicked by AFT024 promoted CD(34)(+) CD(38)(-) cells to proliferate extensively and undergo more asymmetric division. CONCLUSIONS: (1) CD(34)(+) CD(38)(-) cells are heterogeneous and composed of various subpopulations with different initial proliferative behavior, including asymmetric division. (2) The hematopoietic microenvironmental mimicked by AFT024 supports the hematopoietic progenitors better than cytokines and single adhesion factor do, for their proliferation extensively and preservation the self-renewal capacity.