RESUMO
Estrogen receptor ß (ERß) is expressed in immune cells and studies have suggested an antiproliferative function of ERß. We detected ERß expression in murine T- and human B-cell lymphoma cell lines and analyzed the effects of estradiol and selective ERß agonists on lymphoma growth in culture and in vivo. Treating the cells with estradiol had minor effects on cell growth, whereas the selective ERß agonists diarylpropionitrile (DPN) and KB9520 showed a strong antiproliferative effect. When grafting mice with murine T-cell lymphoma cells, male mice developed larger tumors compared with female mice, a difference that was abolished following ovariectomy, showing estrogen-dependent growth in vivo. To investigate whether lymphoma growth may be inhibited in vivo by ERß agonist treatment, mice grafted with murine lymphoma cells were treated with DPN or KB9520. Both ERß-selective agonists strongly inhibited lymphoma growth. The reduced tumor size seen following either DPN or KB9520 treatment was due to reduced proliferation and increased apoptosis. Our results show an ERß ligand-dependent antiproliferative effect of lymphoma cells expressing endogenous ERß and that lymphoma cell growth in vivo can efficiently be inhibited by ERß agonists. This suggests that ERß agonists may be useful in the treatment of lymphomas.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Receptor beta de Estrogênio/agonistas , Linfoma de Células T/tratamento farmacológico , Proteínas de Neoplasias/agonistas , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Nitrilas/uso terapêutico , Propionatos/uso terapêutico , Animais , Antineoplásicos Hormonais/farmacologia , Apoptose/efeitos dos fármacos , Linfoma de Burkitt/patologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estradiol/farmacologia , Receptor beta de Estrogênio/biossíntese , Receptor beta de Estrogênio/fisiologia , Feminino , Humanos , Neoplasias Hepáticas Experimentais/patologia , Linfoma de Células T/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/fisiologia , Transplante de Neoplasias , Nitrilas/farmacologia , Ovariectomia , Propionatos/farmacologia , Especificidade da Espécie , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The prevalence of hepatitis B, C, E, and G viruses, Epstein-Barr virus, and type 6 herpesvirus was studied in Russian and Norwegian patients with Sjogren's disease. The incidence of HBV, HCV, HEV, and HGV markers in Russian patients was higher than in donors. The incidence of serological markers of Epstein-Barr and type 6 herpesvirus was virtually the same in the patients with Sjogren's disease and donors. Epstein-Barr virus DNA was less frequently detected in patients with Sjogren's disease than in donors, as was shown by blood and salivary DNA testing.
