Papers - Seki Tomohiro

PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study Reviewed

Tomohiro Sek, Yu Saida, Shun Kishimoto, Jisook Lee, Yasunori Otowa, Kazutoshi Yamamoto, Gadisetti VR Chandramouli, Nallathamby Devasahayam, James B. Mitchell, Murali C. Krishna, Jeffery R. Brende

Neoplasia   30   100793   2022.05

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier  

Purpose
PEGylated human hyaluronidase (PEGPH20) enzymatically depletes hyaluronan, an important component of the extracellular matrix, increasing the delivery of therapeutic molecules. Combinations of chemotherapy and PEGPH20, however, have been unsuccessful in Phase III clinical trials. We hypothesize that by increasing tumor oxygenation by improving vascular patency and perfusion, PEGPH20 will also act as a radiosensitization agent.
Experimental Design
The effect of PEGPH20 on radiation treatment was analyzed with respect to tumor growth, survival time, p02, local blood volume, and the perfusion/permeability of blood vessels in a human pancreatic adenocarcinoma BxPC3 mouse model overexpressing hyaluronan synthase 3 (HAS3).
Results
Mice overexpressing HAS3 developed fast growing, radiation resistant tumors that became rapidly more hypoxic as time progressed. Treatment with PEGPH20 increased survival times when used in combination with radiation therapy, significantly more than either radiation therapy or PEGPH20 alone. In mice that overexpressed HAS3, EPR imaging showed an increase in local pO2 that could be linked to increases in perfusion/permeability and local blood volume immediately after PEGPH20 treatment. Hyperpolarized [1-13C] pyruvate suggested PEGPH20 caused a metabolic shift towards decreased glycolytic flux. These effects were confined to the mice overexpressing HAS3 - no effect of PEGPH20 on survival, radiation treatment, or pO2 was seen in wild type BxPC3 tumors.
Conclusions
PEGPH20 may be useful for radiosensitization of pancreatic cancer but only in the subset of tumors with substantial hyaluronan accumulation. The response of the treatment may potentially be monitored by non-invasive imaging of the hemodynamic and metabolic changes in the tumor microenvironment.

DOI： 10.1016/j.neo.2022.100793

Study of Polymer Nanofilms Using for High-Throughput Screening in the Development of Transdermal Therapeutic System Reviewed

70 ( 12 )   868 - 875   2022.12

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DOI： 10.1248/cpb.c22-00457

Study on a Novel Transdermal Therapeutic System that Combines the Achievement of Supersaturation by pH-shift Method and User–Activated System Reviewed

Takahiro Suzuki, Tomohiro Seki, Toshinobu Seki

Journal of Pharmaceutical Innovation   18   999 - 1009   2023

Preparation and Characterization of a Glutathione-Responsive Doxorubicin Prodrug Modified by 2-Nitrobenzenesulfonamide Group—Its Selective Cytotoxicity Toward Cells with Enhanced Glutathione Production Reviewed

Tomona Yukimura, Tomohiro Seki and Toshinobu Seki

International Journal of Molecular Sciences.   26 ( 9 )   4128   2025.04

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Authorship：Corresponding author  

Directly monitoring the dynamic in vivo metabolisms of hyperpolarized 13C-oligopeptides Reviewed International coauthorship

Yohei Kondo, Yutaro Saito, Tomohiro Seki, Yoichi Takakusagi, Norikazu Koyasu, Keita Saito, Jumpei Morimoto, Hiroshi Nonaka, Koichiro Miyanishi, Wataru Mizukami, Makoto Negoro, Abdelazim E. Elhelaly, Fuminori Hyodo, Masayuki Matsuo, Natarajan Raju, Rolf E. Swenson, Murali C. Krishna, Kazutoshi Yamamoto, Shinsuke Sando

Science Adv.   10 ( 42 )   eadp2533   2024