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1.
Pediatr Blood Cancer ; 71(10): e31223, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39054702

RESUMEN

Blinatumomab is a bispecific T-cell engager administered as a 28-day continuous infusion. Infusions can be associated with interruptions requiring support from clinical staff, but the frequency of interventions with outpatient blinatumomab has not been characterized. This study is a single-center, retrospective review of patients who received blinatumomab between December 3, 2014 and October 31, 2021 to determine frequency and type of interventions. Forty patients received blinatumomab for 69 cycles. Clinical staff intervention was required in 31 (45%) cycles, only six (8.7%) cycles needed readmission. Management of outpatient blinatumomab infusions requires education and training of clinical staff and caregivers to quickly troubleshoot interruptions.


Asunto(s)
Anticuerpos Biespecíficos , Readmisión del Paciente , Humanos , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/uso terapéutico , Estudios Retrospectivos , Niño , Masculino , Femenino , Preescolar , Adolescente , Readmisión del Paciente/estadística & datos numéricos , Infusiones Intravenosas , Estudios de Seguimiento , Lactante , Pronóstico , Antineoplásicos/administración & dosificación
2.
J Med Chem ; 57(14): 6092-104, 2014 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-24940640

RESUMEN

Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic target or biomarker for several diseases including aggressive cancer, arthritis, and parasitic infections. The development of probes capable of assessing CTB activity in cell lysates, living cells, and animal models of disease are needed to understand its role in disease progression. However, discovering probes selective to cathepsin B over other cysteine cathepsins is a significant challenge due to overlap of preferred substrates and binding site homology in this family of proteases. Herein we report the synthesis and detailed evaluation of two prodrug-inspired fluorogenic peptides designed to be efficient and selective substrate-based probes for CTB. Through cell lysate and cell assays, a promising lead candidate was identified that is efficiently processed and has high specificity for CTB over other cysteine cathepsins. This work represents a key step toward the design of rapid release prodrugs or substrate-based molecular imaging probes specific to CTB.


Asunto(s)
Antineoplásicos/farmacología , Catepsina B/antagonistas & inhibidores , Colorantes Fluorescentes/farmacología , Profármacos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Catepsina B/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , Células HeLa , Humanos , Microscopía Fluorescente , Estructura Molecular , Péptidos/síntesis química , Péptidos/química , Profármacos/síntesis química , Profármacos/química , Relación Estructura-Actividad
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