首页|Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

扫码查看
原文链接
  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
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 de-livery 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 infor-mation 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.

Pulmonary metastasesColorectal cancerAdjuvant chemotherapyIn vivo lung chemo-perfusionSolid-phase microextraction(SPME)microprobesSpatial metabolomics

Mariola Olkowicz、Khaled Ramadan、Hernando Rosales-Solano、Miao Yu、Aizhou Wang、Marcelo Cypel、Janusz Pawliszyn

展开 >

Department of Chemistry,University of Waterloo,Waterloo,ON,Canada

Jagiellonian Centre for Experimental Therapeutics(JCET),Jagiellonian University,Krakow,Poland

Lamer Thoracic Surgery Research Laboratories,Toronto General Hospital Research Institute,University Health Network,Toronto,ON,Canada

The Jackson Laboratory,JAX Genomic Medicine,Farmington,CT,USA

Division of Thoracic Surgery,Department of Surgery,University Health Network,University of Toronto,Toronto Lung Transplant Program,Toronto,ON,Canada

展开 >

Canadian Institute of Health Research(CIHR)-Natural Sciences and Engineering Research Council(NSERC)of Canada Collaborative NSERC through the Industrial Research Chair(IRC)program

355935IRCPJ 184412e15

2024

10.1016/j.jpha.2023.08.001

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(2)
  • 52