title: Different combination schedules of gemcitabine with endostar affect antitumor efficacy.
abstract: OBJECTIVE
  Antiangiogenic drugs inhibit tumor growth by decreasing blood supply and causing transient "normalization" of the tumor vasculature, thereby improving the delivery of systemic chemotherapy. A higher dose of antiangiogenic drugs may lead to a more marked decrease in intratumoral blood flow but may concomitantly cause a decrease in delivery of chemotherapeutic agents. The purpose of this study was to define an optimal schedule for the combination of gemcitabine with a recombinant endostatin, endostar.
  
  
  METHODS
  We evaluated the antitumor effects with different schedules of gemcitabine combined with or without endostar. The changes of vascular endothelial growth factor (VEGF) levels in tumor extracts and sera after gemcitabine treatment were examined. Endostar was also assessed for its abilities to inhibit the increase in VEGF levels. Apoptotic cells and microvessel density within tumor tissue were also examined.
  
  
  RESULTS
  Endostar administered simultaneously with or following gemcitabine improved the inhibition of tumor growth, compared with gemcitabine alone. VEGF levels decreased immediately after gemcitabine treatment, but increased in the following several days. Endostar administered simultaneously with or following gemcitabine could inhibit the increase in VEGF levels, thereby cause a decreased vessel density and an increased apoptosis in tumor tissue.
  
  
  CONCLUSIONS
  Our finding suggested that endostar given simultaneously with or following gemcitabine might be optimal to enhance the antitumor effect.
authors.affiliation: Department of Medical Oncology, Cancer Center, The State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, No. 37, Guo Xue Xiang, Chengdu 610041, Sichuan Province, China.
authors.forename: Xing-Chen
authors.initials: XC
authors.lastname: Peng
authors.forename: Meng
authors.initials: M
authors.lastname: Qiu
authors.forename: Meng
authors.initials: M
authors.lastname: Wei
authors.forename: Ben-Xu
authors.initials: BX
authors.lastname: Tan
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Gong
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Bi
authors.forename: Ji-Yan
authors.initials: JY
authors.lastname: Liu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D043169:Endostatins / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D000093542:Gemcitabine
chemical_list: D043169:Endostatins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; C522911:endostar protein; D000093542:Gemcitabine