RESUMO
Allogeneic stem cell transplantation (SCT) from an HLA-matched sibling donor (MSD) is a postremission treatment that offers a potential cure for adults with cytogenetically normal (CN) acute myelogenous leukemia (AML) in first complete remission (CR1). The best alternative in the absence of an MSD remains unclear, however. The aim of this study was to retrospectively compare the outcomes of autologous peripheral blood stem cell transplantation (auto-PBSCT; n = 177) and allogeneic bone marrow transplantation (BMT) from an HLA-matched unrelated donor (MUD; n = 173) in adult patients with CN-AML/CR1. Both the multivariate analysis (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.71 to 1.97; P = .53) and propensity score models (HR, 1.40; 95% CI, 0.80 to 2.43; P = .24) indicated that the leukemia-free survival (LFS) rate of auto-PBSCT was not significantly different from that of MUD-BMT. These results suggest that in the absence of an available MSD, auto-PBSCT remains a viable alternative as postremission therapy in patients with CN-AML/CR1.
Assuntos
Antineoplásicos/uso terapêutico , Transplante de Medula Óssea/métodos , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Doadores não Relacionados/estatística & dados numéricos , Adulto , Feminino , Humanos , Cariótipo , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Irmãos , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
The deposition of amyloid beta (Abeta) protein is a consistent pathological hallmark of Alzheimer's disease (AD) brains; therefore, inhibition of Abeta fibril formation and destabilization of pre-formed Abeta fibrils is an attractive therapeutic and preventive strategy in the development of disease-modifying drugs for AD. This study demonstrated that Paeonia suffruticosa, a traditional medicinal herb, not only inhibited fibril formation of both Abeta(1-40) and Abeta(1-42) but it also destabilized pre-formed Abeta fibrils in a concentration-dependent manner. Memory function was examined using the passive-avoidance task followed by measurement of Abeta burden in the brains of Tg2576 transgenic mice. The herb improved long-term memory impairment in the transgenic mice and inhibited the accumulation of Abeta in the brain. Three-dimensional HPLC analysis revealed that a water extract of the herb contained several different chemical compounds including 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (PGG). No obvious adverse/toxic were found following treatment with PGG. As was observed with Paeonia suffruticosa, PGG alone inhibited Abeta fibril formation and destabilized pre-formed Abeta fibrils in vitro and in vivo. Our results suggest that both Paeonia suffruticosa and its active constituent PGG have strong inhibitory effects on formation of Abeta fibrils in vitro and in vivo. PGG is likely to be a safe and promising lead compound in the development of disease-modifying drugs to prevent and/or cure AD.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Taninos Hidrolisáveis/farmacologia , Memória/efeitos dos fármacos , Paeonia/química , Extratos Vegetais/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Fragmentos de Peptídeos/metabolismo , Fitoterapia/métodos , Fatores de TempoRESUMO
Because the deposition of beta-amyloid protein (Abeta) is a consistent pathological hallmark of Alzheimer's disease (AD) brains, inhibition of Abeta generation, prevention of Abeta fibril formation, or destabilization of preformed Abeta fibrils would be attractive therapeutic strategies for the treatment of AD. We examined the effects of several medicinal herbs used in traditional Chinese medical formulae on the formation and destabilization of Abeta fibrils by using the thioflavin T binding assay, atomic force microscopic imaging, and electrophoresis. Our study demonstrates that several of these herbs have potent inhibitory effects on fibril formation of both Abeta(1-40) and Abeta(1-42) in concentration-dependent manners; in particular, Uncaria rhynchophylla inhibited Abeta aggregation most intensively. Significant destabilization of preformed Abeta(1-40) and Abeta(1-42) fibrils was also induced by Uncaria rhynchophylla as well as some other herb extracts. Three-dimensional HPLC analysis indicated that the water extract of this herb contains several different chemical compounds, including oxindole and indol alkaloids, which have been regarded as neuroprotective. Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Abeta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD.