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1.
J Thorac Oncol ; 18(8): 1070-1081, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37094664

RESUMO

INTRODUCTION: Thymic malignancies are rare tumors with few therapeutic options. The STYLE trial was aimed to evaluate activity and safety of sunitinib in advanced or recurrent type B3 thymoma (T) and thymic carcinoma (TC). METHODS: In this multicenter, Simon 2 stages, phase 2 trial, patients with pretreated T or TC were enrolled in two cohorts and assessed separately. Sunitinib was administered 50 mg daily for 4 weeks, followed by a 2-week rest period (schedule 4/2), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Progression-free survival, overall survival, disease control rate and safety were secondary endpoints. RESULTS: From March 2017 to January 2022, 12 patients with T and 32 patients with TC were enrolled. At stage 1, ORR was 0% (90% confidence interval [CI]: 0.0-22.1) in T and 16.7% (90% CI: 3.1-43.8) in TC, so the T cohort was closed. At stage 2, the primary endpoint was met for TC with ORR of 21.7% (90% CI: 9.0%-40.4%). In the intention-to-treat analysis, disease control rate was 91.7% (95% CI: 61.5%-99.8%) in Ts and 89.3% (95% CI: 71.8%-97.7%) in TCs. Median progression-free survival was 7.7 months (95% CI: 2.4-45.5) in Ts and 8.8 months (95% CI: 5.3-11.1) in TCs; median overall survival was 47.9 months (95% CI: 4.5-not reached) in Ts and 27.8 months (95% CI: 13.2-53.2) in TCs. Adverse events occurred in 91.7% Ts and 93.5% TCs. Grade 3 or greater treatment-related adverse events were reported in 25.0% Ts and 51.6% TCs. CONCLUSIONS: This trial confirms the activity of sunitinib in patients with TC, supporting its use as a second-line treatment, albeit with potential toxicity that requires dose adjustment.


Assuntos
Neoplasias Pulmonares , Timoma , Neoplasias do Timo , Humanos , Sunitinibe/uso terapêutico , Timoma/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias do Timo/patologia , Intervalo Livre de Progressão
2.
Cell Mol Life Sci ; 79(1): 7, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936028

RESUMO

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons and severe muscle atrophy without effective treatment. Most research on the disease has been focused on studying motor neurons and supporting cells of the central nervous system. Strikingly, the recent observations have suggested that morpho-functional alterations in skeletal muscle precede motor neuron degeneration, bolstering the interest in studying muscle tissue as a potential target for the delivery of therapies. We previously showed that the systemic administration of the P2XR7 agonist, 2'(3')-O-(4-benzoylbenzoyl) adenosine 5-triphosphate (BzATP), enhanced the metabolism and promoted the myogenesis of new fibres in the skeletal muscles of SOD1G93A mice. Here we further corroborated this evidence showing that intramuscular administration of BzATP improved the motor performance of ALS mice by enhancing satellite cells and the muscle pro-regenerative activity of infiltrating macrophages. The preservation of the skeletal muscle retrogradely propagated along with the motor unit, suggesting that backward signalling from the muscle could impinge on motor neuron death. In addition to providing the basis for a suitable adjunct multisystem therapeutic approach in ALS, these data point out that the muscle should be at the centre of ALS research as a target tissue to address novel therapies in combination with those oriented to the CNS.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/administração & dosagem , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Axônios/patologia , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Denervação , Modelos Animais de Doenças , Progressão da Doença , Feminino , Membro Posterior/patologia , Humanos , Inflamação/patologia , Injeções Intramusculares , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Transgênicos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/inervação , Atrofia Muscular/patologia , Fenótipo , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Células Satélites de Músculo Esquelético/patologia , Células de Schwann/patologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia
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