title: Metronomic irinotecan chemotherapy combined with ultrasound irradiation for a human uterine sarcoma xenograft.
abstract: Metronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic irinotecan combined with low-intensity ultrasound (US) in human uterine sarcoma and evaluated its antiangiogenesis mechanism by measuring the circulating endothelial progenitor cells (CEP), a surrogate marker of angiogenesis. A human uterine sarcoma cell line, FU-MMT-3, was used in the present study because this tumor is one of the most malignant neoplasms of human solid tumors and it also has a high angiogenesis property. The combination of low-dose irinotecan and US irradiation significantly inhibited the tube formation of HUVEC and vascular endothelial growth factor expression of tumor cells in vitro. The FU-MMT-3 xenografts in nude mice were treated using US at a low intensity (2.0 w/cm(2), 1 MHz) for 4 min three times per week each after the intraperitoneal administration of irinotecan; this treatment was continued for 5 weeks. The tumor vascularity was assessed by contrast-enhanced color Doppler US in real time. The combination treatment significantly inhibited the mobilization of CEP and intratumoral vascularity compared with the control. This combination therapy showed a significant reduction in tumor volume, resulting in a significant prolongation of survival, in comparison with each treatment alone. These results suggest that the effect of metronomic chemotherapy for human uterine sarcoma was accelerated by US irradiation in vivo and this combination might therefore be potentially effective for new cancer therapy.
authors.affiliation: Departments of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Batsuren
authors.initials: B
authors.lastname: Choijamts
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Naganuma
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tachibana
authors.forename: Makoto
authors.initials: M
authors.lastname: Emoto
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D002469:Cell Separation; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D012509:Sarcoma / Q000628:therapy*; D014464:Ultrasonic Therapy / Q000379:methods*; D014594:Uterine Neoplasms / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin