Molecular targeting of neuroblastoma with a novel p16INK4a transporter system

Kawaguchi,Takuya; Yoshikawa,Kazuhiro; Kawamoto,Keiji; Yoshimura,Kunikazu; Oshige,Hideyuki; Asai,Akio

doi:10.3892/ijo.2014.2372

Molecular targeting of neuroblastoma with a novel p16INK4a transporter system

Authors:
- Takuya Kawaguchi
- Kazuhiro Yoshikawa
- Keiji Kawamoto
- Kunikazu Yoshimura
- Hideyuki Oshige
- Akio Asai
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Affiliations: Department of Neurosurgery, Kansai Medical University, Moriguchi City, Osaka 570-8507, Japan, Second Department of Pathology, Aichi Medical University School of Medicine, Yazago, Nagakute City, Aichi 480-1195, Japan, Higashi Oosakayamaji Hospital, Higashiosaka City, Osaka 578-0925, Japan, Department of Neurosurgery, Kansai Medical University, Hirakata City, Osaka 573-1191, Japan
Published online on: April 7, 2014 https://doi.org/10.3892/ijo.2014.2372
Pages: 1879-1885

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Abstract

Potential molecular targets in neuroblastoma include ALK mutations, p16 deletion and CDK2A mutations; however, targeted therapeutics have not been developed for these factors. We developed Wr-T, a new system for intracellular peptide and protein delivery with a 30-residue sequence that mediates molecule entrapment and intracellular permeability. Wr-T was used to introduce the p16INK4a functional peptide to restore the tumor suppressor function of p16INK4a. Introduction of Wr-T into rats with subcutaneous grafts of neuroblastoma produced an astonishing 75.6% tumor suppression (p<0.0005). Thus, the p16INK4a functional peptide can be introduced in low doses and, because it exists in vivo, it should produce fewer side-effects than standard chemotherapy. We suggest this system could be used for molecular-targeted peptides other than p16INK4a and should be pursued for further development.

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