title: Chemoembolization of rat liver metastasis with microspheres and gemcitabine followed by evaluation of tumor cell load by chemiluminescence.
abstract: An orthotopic, isogenic rat model was used to determine the potential of chemoembolization (CHE) for reducing the tumor cell load of a diffusely metastatic liver. Seven days after injecting CC531-lac-Z cells intraportally to male WAG/Rij rats, tumor positive animals were treated by injection into the hepatic artery with solvent (n=17), degradable starch microspheres (DSM, 30 mg/kg; n=16), DSM plus 5-fluorouracil (5-FU, dosages: 90, 60, and 40 mg/kg) or DSM plus gemcitabine (Gem, dosages: 100, 80, 50, and 10 mg/kg). After 3 more weeks the experiment was terminated, the livers were weighted and the number of CC531-lac-Z cells per liver was determined. Injection of DSM reduced the tumor cell load by 21% (T/C%=79), the combination with 5-FU caused a stimulation of growth at 40 mg/kg (T/C%=291; n=10), but effected dose-dependent reductions in tumor cell number at 60 mg/kg (T/C%=86; n=16), and 90 mg/kg (T/C=19; n=17). None of these effects was significantly different from controls. The combination of DSM plus Gem was toxic at the highest dose (100 mg/kg), but well tolerated and highly effective at 80 mg/kg (T/C%= 16; n=12), 50 mg/kg (T/C%=9; n=12), and 10 mg/kg (T/C%=26; n=14). These results were significantly different from controls (p<0.05), respectively. In summary, the comparison of CHE with 5-FU or Gem shows that the efficacy of Gem in reducing the hepatic tumor cell load was significantly higher and its therapeutic ratio was greater than that of 5-FU.
authors.affiliation: University Clinics Muenster, Department of General Surgery, D-48129 MYnster, Germany. smseelig@gmx.net
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Seelig
authors.forename: Meike
authors.initials: M
authors.lastname: Leible
authors.forename: Jan
authors.initials: J
authors.lastname: Sänger
authors.forename: Martin R
authors.initials: MR
authors.lastname: Berger
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D016461:Chemoembolization, Therapeutic; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008297:Male; D008863:Microspheres; D009368:Neoplasm Transplantation; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D047368:Tumor Burden; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine