RESUMO
T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy associated with unfavorable factors including male gender and over nine years of age. Chemotherapy toxicity continues to present a major challenge. There is a need to develop novel natural agents to improve survival and quality of life in patients with T-ALL. 20(S)-ginsenoside Rh2 (GRh2) exhibits immune regulation and anti-tumor effects in both cellular and murine xenograft models. In the present study, the anti-cancer mechanisms of 20(S)-GRh2 involved in the immune system and intestinal microbiota were investigated in T-ALL mice. We revealed that 20(S)-Rh2 suppressed T-ALL by blocking the PI3K/Akt/mTOR signaling pathway, and enhanced immunity in the spleen by regulating immune factors. In addition, 20(S)-GRh2 altered the composition of the gut microbiota, and promoted intestinal homeostasis by elevating the levels of tight junction proteins, antimicrobial peptides and IgA. 20(S)-GRh2 ameliorated the LPS-induced inflammatory response in the intestine of T-ALL mice. Furthermore, Bacteroidetes, Verrucomicrobia, Akkermansia, Lactobacillus, and Lachnospiraceae_NK4A136_group were positively correlated with anti-tumor immune factors, intestinal barrier-related factors, and the anti-inflammatory response. Conversely, Firmicutes, Proteobacteria, Parabacteroides and Alistipes had the opposite correlation. Collectively, these results suggest that 20(S)-GRh2 is a safe and effective natural product, that shows promise for the prevention and treatment of T-ALL.
Assuntos
Antineoplásicos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ginsenosídeos/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/microbiologia , Animais , Linhagem Celular Tumoral , Homeostase/efeitos dos fármacos , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We report a case of pulmonary mucormycosis in a patient with T-cell acute lymphoblastic leukemia. The diagnosis of mucormycosis was initially based on mycological examination of a pulmonary specimen. However, we describe how it could have been made 2 months earlier using polymerase chain reaction assays targeting Mucorales species on serum specimens.
Assuntos
DNA Fúngico/sangue , Mucorales/isolamento & purificação , Mucormicose/diagnóstico por imagem , Adolescente , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Pulmão/microbiologia , Mucormicose/sangue , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/microbiologia , Tórax/diagnóstico por imagem , Tórax/microbiologia , Tomografia Computadorizada por Raios XRESUMO
Children with hematologic malignancies are at an increased risk of invasive fungal infections and a greater risk has been seen with exposure to building construction. Prophylaxis with high-dose (IV) liposomal amphotericin B (L-AmB) 10 mg/kg once weekly was initiated in our high risk children based on previous pharmacokinetic studies. This treatment regimen was associated with a 26% incidence of adverse infusion reactions.