Enhancement of antitumor effect of micelle-incorporated anticancer drug by high concentration NaCl

• Project/Area Number: 15K20191
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Kanazawa University
• Principal Investigator: UENO TAKAYOSHI 金沢大学, 附属病院, 助教 (30623649)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 頭頸部癌 / 抗癌剤 / ミセル化 / 化学療法 / ミセル化薬剤 / ミセル

Outline of Final Research Achievements

The micelle-incorporated cisplatin releases cisplatin which exhibits antitumor effect by disintegration of micelles. Micellization improves the stability of the drug in blood and increases the tumor concentration. However, the antitumor effect is lower than the accumulation effect. It was found that the micelle-incorporated cisplatin dissolved in high concentration NaCl had a high antitumor effect in vitro. However, in the head and neck cancer mouse model, the enhancement of the antitumor effect could not be confirmed.

Academic Significance and Societal Importance of the Research Achievements

現在のところ、頭頸部癌においてシスプラチンを凌駕する抗がん剤も分子標的薬もない。このシスプラチンの副作用軽減と効果を増強する方法の一つとしてミセル化がある。腫瘍への薬剤集積の増加に比して、抗腫瘍効果がの上昇が少なく、ミセル化薬剤が徐放性である点が問題と考えた。シスプラチンは濃度依存性薬剤のため、ミセルの崩壊を人為的に早めることができれば抗腫瘍効果が高まるのではないかと考えた。想定したような結果は得られなかったが、引き続き癌の治癒率を高めるための手段を検討することは重要であると考える。

Research Products

• [Journal Article] Expression and subcellular localisation of AID and APOBEC3 in adenoid and palatine tonsils (2018)
  • Author(s): Seishima Noriko、Kondo Satoru、Wakae Kousho、Wakisaka Naohiro、Kobayashi Eiji、Kano Makoto、Moriyama-Kita Makiko、Nakanishi Yosuke、Endo Kazuhira、Imoto Tomoko、Ishikawa Kazuya、Sugimoto Hisashi、Hatano Miyako、Ueno Takayoshi、Koura Miki、Kitamura Koichi、Muramatsu Masamichi、Yoshizaki Tomokazu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 918-918
  • DOI: 10.1038/s41598-017-18732-w
  • NAID: 120006602142
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Modulation of Tumor Microenvironment by Epstein-Barr virus Latent Membrane Protein-1 in Nasopharyngeal Carcinoma (2018)
  • Author(s): Yoshizaki T, Kondo S, Endo K, Nakanishi Y, Aga M, Kobayashi E, Hirai N, Sugimoto H, Hatano M, Ueno T, Ishikawa K, Wakisaka N
  • Journal Title: Cancer Sci Volume: 109 Issue: 2 Pages: 272-278
  • DOI: 10.1111/cas.13473
  • Peer Reviewed
• [Presentation] 上咽頭癌をはじめとした頭頸部癌における血中循環腫瘍細胞の検出方法の開発 (2018)
  • Author(s): 上野貴雄、近藤悟、吉崎智一
  • Organizer: 第31回日本口腔・咽頭科学会
• [Presentation] Assessment of antitumor activity and acute peripheral neuropathy of 1,2-diaminocyclohexane platinum (II)-incorporating micelles (NC-4016) (2015)
  • Author(s): Takayoshi Ueno
  • Organizer: the 3rd Congress of European ORL-HNS
  • Place of Presentation: チェコ プラハ
  • Year and Date: 2015-06-07
  • Int'l Joint Research