title: Metabolism of tumors under treatment: mapping of metabolites with quantitative bioluminescence.
abstract: OBJECTIVE
  The metabolic switch to aerobic glycolysis (Warburg effect) and enhanced lactate production is characteristic for aggressive tumor cells and is a co-determining factor for tumor response and treatment outcome. Thus analysis of the metabolic status under treatment is important to understand and improve treatment modalities.
  
  
  METHODS
  Metabolite concentrations were determined by the immersion of tumor sections in an ATP, lactate or glucose-depending luciferase-containing buffer system. Integrated light output is detected in a bioluminescent detection system.
  
  
  RESULTS
  Mice carrying tumor xenografts derived from A549 lung cancer cells were treated with the microtubule stabilizing agent patupilone, ionizing radiation or in combination. Lactate levels were significantly reduced and glucose levels drastically increased in comparison to untreated tumors. Interestingly, these changes were only minimal in tumors derived from patupilone-resistant but otherwise isogenic A549EpoB40 cells. ATP levels of all tumors tested did not change under any treatment. When compared with histological endpoints, basal and treatment-dependent changes of lactate levels in the different tumors mainly correlated with the proliferative activity and the tumor growth response to treatment.
  
  
  CONCLUSIONS
  This study shows that the tumor metabolism is responsive to different treatment modalities and could eventually be used as an early surrogate marker for treatment response.
authors.affiliation: Department of Radiation Oncology, University Hospital Zürich, Switzerland.
authors.forename: Angela
authors.initials: A
authors.lastname: Broggini-Tenzer
authors.forename: Van
authors.initials: V
authors.lastname: Vuong
authors.forename: Martin
authors.initials: M
authors.lastname: Pruschy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D034261:Epothilones / Q000494:pharmacology; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D008156:Luciferases; D008163:Luminescent Measurements; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: D034261:Epothilones; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D008156:Luciferases; C093788:epothilone B