RESUMO
We describe the synthesis and biological testing of ruthenium-bipyridine ruxolitinib (RuBiRuxo), a photoreleasable form of ruxolitinib, a JAK inhibitor used as an antitumoral agent in cutaneous T-cell lymphomas (CTCL). This novel caged compound is synthesized efficiently, is stable in aqueous solution at room temperature, and is photoreleased rapidly by visible light. Irradiation of RuBiRuxo reduces cell proliferation and induces apoptosis in a light- and time-dependent manner in a CTCL cell line. This effect is specific and is mediated by a decreased phosphorylation of STAT proteins. Our results demonstrate the potential of ruthenium-based photocompounds and light-based therapeutic approaches for the potential treatment of cutaneous lymphomas and other pathologies.
Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Nitrilas , Pirazóis , Pirimidinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Nitrilas/química , Nitrilas/farmacologia , Nitrilas/síntese química , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/síntese química , Apoptose/efeitos dos fármacos , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Linhagem Celular Tumoral , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/química , Inibidores de Janus Quinases/síntese química , Rutênio/química , Rutênio/farmacologia , Luz , Estrutura Molecular , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismoRESUMO
OBJECTIVE: Several studies have reported unique ethnic phenotypes of inflammatory bowel disease (IBD). An appreciation of disease manifestations in different populations may improve clinical outcomes. There are no studies examining IBD in patients of Haitian or Cape Verdean descent. We sought to define the IBD phenotype in these populations. MATERIALS AND METHODS: This was a retrospective review comparing Haitian and Cape Verdean immigrant IBD patients to Caucasians, all receiving care at Boston Medical Center in Boston, Massachusetts, USA. The following variables were analyzed: family history, smoking history, vaccinations/cancer screening, age of diagnosis, disease duration, disease location, medication use, and complications. RESULTS: Thirty-one Haitians and 21 Cape Verdeans were matched to Caucasian controls. Haitians (mean age 42 years) and Cape Verdeans (mean age 47 years) with Crohn's disease were diagnosed with IBD later than Caucasians (mean age 31 years, p = 0.04 and 0.02, respectively). Haitians with Crohn's were less likely to have a history of tobacco use compared to Caucasians (13% vs. 51%, p = 0.02). Cape Verdeans with Crohn's were less likely to have perianal involvement (0% vs. 50%, p = 0.01). Haitians with IBD were less likely to have ever used glucocorticoids (48% vs. 76%, p = 0.02). There was no difference in vaccination rates, cancer screening, or disease complications. CONCLUSIONS: This study demonstrates differences in IBD presentation and disease course among Haitians and Cape Verdeans. Our results suggest a more mild disease in these ethnic groups. Future studies are needed to identify the influence of environmental factors.