In vivo evaluation of macromolecular antitumor agent, P-THP, in pancreatic cancer
Project/Area Number |
26860031
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Physical pharmacy
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Research Institution | Sojo University |
Principal Investigator |
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | すい臓がん / ピラルビシン / 高分子ポリマー / HPMA / 高分子化抗がん剤 / 高分子抗がん剤 |
Outline of Final Research Achievements |
Many conjugates of water-soluble polymers with biologically active molecules were developed. However, therapeutic effects of these conjugates do not depend only on the structures and properties of the polymer carriers; they are strongly influenced by properties and mechanisms of action of the attached drugs. Pirarubicin (THP), a tetrahydropyranyl derivative of doxorubicin (DOX), demonstrated more rapid cellular internalization and potent cytotoxicity than DOX. Here, we conjugated the THP or DOX to HPMA polymer via a hydrazone bond. The polymer prodrugs P-THP and P-DOX, respectively, had comparable hydrodynamic sizes and drug loading. Compared with P-DOX, P-THP showed approximately 10 times greater cellular uptake and a cytotoxicity. No significant difference occurred in the tumor drug concentration during 6-24 h after drug administration. Antitumor activity against xenograft human pancreatic tumor (SUIT2) in mice was greater for P-THP than for P-DOX.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases.2016
Author(s)
Dozono H, Yanazume S, Nakamura H, Etrych T, Chytil P, Ulbrich K, Fang J, Arimura T, Douchi T, Kobayashi H, Ikoma M, Maeda H.
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Journal Title
Target Oncol
Volume: 11
Issue: 1
Pages: 101-106
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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