title: A model of primary culture of colorectal cancer and liver metastasis to predict chemosensitivity.
abstract: BACKGROUND
  Prediction of chemosensitivity is a major goal of modern oncology. The aim of this study was to establish a simple and effective model of primary culture of colorectal cancer fragments and to test whether it allows prediction of chemosensitivity.
  
  
  METHODS
  Colorectal cancer fragments (primary tumors or liver metastases) of 94 consecutive and previously untreated patients were obtained, prepared, and cultured in polyHEMA. For each fragment cultured, a proliferative index (PI) was calculated after immunostaining at d 0 and after 7 d in culture with media alone or supplemented for 24h with the topoisomerase I inhibitor metabolite SN-38. The correlation between in vitro response (decrease in PI after exposure to the drug) and in vivo response (RECIST criteria) was studied in a subset of patients who had measurable metastases and were treated with a topoisomerase I inhibitor.
  
  
  RESULTS
  PolyHEMA allowed three-dimensional culture of tumor fragments up to 7 d without fibroblastic invasion and with a slight but significant decrease of PI (59% at d 0 versus 51% after 7 d in culture, P < 0.001). In vitro drug efficacy was tested in 67 fragments, the mean PI after culture with SN-38 dropped to 22% (P < 0.001). In a subset of 12 patients, there was no statistically significant correlation between in vitro and in vivo response (P = 0.13).
  
  
  CONCLUSIONS
  Primary culture in polyHEMA was easy to perform successfully in 71% of cases. On this model, the antiproliferative effect of SN-38 could be measured and results correlated to clinical data.
authors.affiliation: Department of Digestive Surgery, AP-HP, Hôpital Ambroise-Paré, Boulogne, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Brouquet
authors.forename: Philippe
authors.initials: P
authors.lastname: Taleb
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lot
authors.forename: Alain
authors.initials: A
authors.lastname: Beauchet
authors.forename: Catherine
authors.initials: C
authors.lastname: Julie
authors.forename: Gregoire
authors.initials: G
authors.lastname: Prevost
authors.forename: Bernard
authors.initials: B
authors.lastname: Nordlinger
authors.forename: Christophe
authors.initials: C
authors.lastname: Penna
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000556:secondary; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D016903:Drug Monitoring / Q000379:methods; D019008:Drug Resistance, Neoplasm; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000556:secondary; D011102:Polyhydroxyethyl Methacrylate / Q000494:pharmacology; D011859:Radiography; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019394:Ki-67 Antigen; D059004:Topoisomerase I Inhibitors; D011102:Polyhydroxyethyl Methacrylate; D000077146:Irinotecan; D002166:Camptothecin