title: Advanced Chemoembolization by Anti-angiogenic Calcium-Phosphate Ceramic Microspheres Targeting the Vascular Heterogeneity of Cancer Xenografts.
abstract: The purpose of the present study was to develop an advanced method of anti-angiogenic chemoembolization to target morphological vascular heterogeneity in tumors and further the therapeutic efficacy of cancer treatment. This new chemoembolization approach was designed using resorbable calcium-phosphate ceramic microspheres (CPMs), in a mixture of three different sizes, which were loaded with an anti-angiogenic agent to target the tumor vasculature in highly angiogenic solid tumors in humans in vivo. The human uterine carcinosarcoma cell line, FU-MMT-3, was used in this study because the tumor is highly aggressive and exhibits a poor response to radiotherapy and chemotherapeutic agents that are in current use. CPMs 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 with TNP-470-loaded CPMs of three different diameters achieved a greater suppression of tumor growth in comparison to treatment with single-size TNP-470-loaded CPMs alone, and the control. Severe loss of body weight was not observed in any mice treated with any size of TNP-470-loaded CPMs. These results suggest that treatment with a mixture of differently-sized anti-angiogenic CPMs might be more effective than treatment with CPMs of a single size. This advanced chemoembolization method, which incorporated an anti-angiogenic agent to target the morphological vascular heterogeneity of tumors may contribute to effective treatment of locally advanced or recurrent solid tumors.
authors.affiliation: Department of Health and Welfare, International University of Health and Welfare, Sawara-ku, Fukuoka, Japan Division of Gynecology in Preventive Medicine, Fukuoka Sanno Hospital, Sawara-ku, Fukuoka, Japan emoto1209@gmail.com mamorua@meiji.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Emoto
authors.affiliation: Department of Applied Chemistry, School of Science and Technology, Meiji University, Tama-ku, Kawasaki, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yoshihisa
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yano
authors.affiliation: Department of Health and Welfare, International University of Health and Welfare, Sawara-ku, Fukuoka, Japan.
authors.forename: Batsuren
authors.initials: B
authors.lastname: Choijamts
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugu
authors.affiliation: Department of Anatomy, Faculty of Medicine, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka, Japan.
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tachibana
authors.affiliation: Department of Applied Chemistry, School of Science and Technology, Meiji University, Tama-ku, Kawasaki, Japan emoto1209@gmail.com mamorua@meiji.ac.jp.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aizawa
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002130:Calcium Phosphates / Q000627:therapeutic use*; D002516:Ceramics / Q000627:therapeutic use*; D016461:Chemoembolization, Therapeutic; D003460:Crystallization; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002130:Calcium Phosphates; D003510:Cyclohexanes; D012717:Sesquiterpenes; C020243:calcium phosphate; D000077609:O-(Chloroacetylcarbamoyl)fumagillol
keywords: Chemoembolization; TNP-470; anti-angiogenic therapy; carcinosarcoma; ceramics; drug delivery system (DDS); microsphere; uterine sarcoma; vascular heterogeneity