title: Cellular parameters predictive of the clinical response of colorectal cancers to irinotecan. A preliminary study.
abstract: BACKGROUND
  We have examined, in this study, the feasibility of determining cellular factors contributing to irinotecan activity in colorectal cancers. Irinotecan is a camptothecin derivative requiting carboxylesterase activation to SN-38, which interacts with its target enzyme, topoisomerase I.
  
  
  METHODS
  In 9 surgical or biopsy samples of colorectal tumours and corresponding normal tissue, kept in a tumour bank, we evaluated topoisomerase I expression and activity, respectively by Western blotting and DNA relaxation assay, carboxylesterase activity using two different substrates and p53 status by immunohistochenistry.
  
  
  RESULTS
  Topoisomerase I expression and activity were significantly correlated, as were the two types of determinations for carboxylesterase activity. Topoisomerase I was significantly more active in tumours than in corresponding normal tissue. The three samples presenting the highest topoisomerase I expression and activity originated from the patients who responded to irinotecan treatment. No such features were apparent for carboxylesterase activity and p53 staining.
  
  
  CONCLUSIONS
  Topoisomerase I expression appeared as the parameter most likely to predict response to irinotecan therapy in the clinical setting.
authors.affiliation: Laboratoire de Pharmacologie des Agents Anticancéreux, Institut Bergonié et Université Victor Segalen Bordeaux 2, 229, cours de l'Argonne 33076 Bordeaux-cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Pavillard
authors.forename: Virginie
authors.initials: V
authors.lastname: Charasson
authors.forename: Audrey
authors.initials: A
authors.lastname: Laroche-Clary
authors.forename: Isabelle
authors.initials: I
authors.lastname: Soubeyran
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015153:Blotting, Western; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D043182:Carboxylesterase / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53; D000077146:Irinotecan; D043182:Carboxylesterase; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin