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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics.
Olkowicz, Mariola; Ramadan, Khaled; Rosales-Solano, Hernando; Yu, Miao; Wang, Aizhou; Cypel, Marcelo; Pawliszyn, Janusz.
Afiliación
  • Olkowicz M; Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
  • Ramadan K; Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
  • Rosales-Solano H; Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
  • Yu M; Department of Chemistry, University of Waterloo, Waterloo, ON, Canada.
  • Wang A; The Jackson Laboratory, JAX Genomic Medicine, Farmington, CT, USA.
  • Cypel M; Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
  • Pawliszyn J; Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
J Pharm Anal ; 14(2): 196-210, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38464782
ABSTRACT
Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Pharm Anal Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Pharm Anal Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: China