Novel chemoembolization using calcium-phosphate ceramic microsphere incorporating TNP-470, an anti-angiogenic agent.
The purpose of the present study was to develop a new method of chemoembolization to improve the therapeutic effectiveness and safety profile of cancer treatment. A chemoembolization approach was designed for human solid tumors using resorbable calcium-phosphate ceramic microspheres loaded with an agent anti-angiogenic to tumor vasculature in vivo. The human uterine sarcoma cell line FU-MMT-3 was used in this study because this tumor is aggressive and also exhibits a poor response to radiotherapy or any chemotherapy currently used. The calcium-phosphate ceramic microspheres loaded with TNP-470, an anti-angiogenic agent, were injected into FU-MMT-3 xenografts in nude mice three times per week for 8 weeks. The treatment using TNP-470-loaded microspheres suppressed tumor growth, compared to treatment with TNP-470 alone, microspheres alone, and the control. The mean tumor weight after treatment using TNP-470-loaded microspheres was significantly lower than that after treatment with microspheres alone. These ceramic microspheres were remarkably embolized in tumor microvessels as well as in the feeding arteries and a significant reduction of intratumoral vascularity was also demonstrated following treatment with TNP-470-loaded microspheres. Severe loss of body weight was not observed in any mice treated with the TNP-470-loaded microspheres, compared to treatment with TNP-470 alone. These results suggest that targeting tumor vasculature in human uterine sarcoma using calcium-phosphate microspheres might be more effective and safer than the treatment that employs anti-angiogenic agent alone. This new chemoembolization method incorporating an anti-angiogenic agent may contribute to the effective treatment of locally advanced or recurrent solid tumors.
Emoto
Makoto
M
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Fukuoka, Japan. emoto@cis.fukuoka-u.ac.jp
Naganuma
Yasuko
Y
Choijamts
Batsuren
B
Ohno
Toshiki
T
Yoshihisa
Hajime
H
Kanomata
Nobuhiko
N
Kawarabayashi
Tatsuhiko
T
Aizawa
Mamoru
M
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents; D002130:Calcium Phosphates; D045744:Cell Line, Tumor; D002516:Ceramics; D003510:Cyclohexanes; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes; D014594:Uterine Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002130:Calcium Phosphates; D003510:Cyclohexanes; D012717:Sesquiterpenes; C020243:calcium phosphate; D000077609:O-(Chloroacetylcarbamoyl)fumagillol