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Updated: Aug 26, 2026

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis
09:42

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis

Published on: June 26, 2019

Selective enhancer of tumor vascular permeability for optimization of cancer chemotherapy

Yasuo Yoshioka1, Yasuo Tsutsumi, Haruhiko Kamada

  • 1Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.

Biological & Pharmaceutical Bulletin
|March 3, 2004
PubMed

Insights

PEGylated tumor necrosis factor-alpha (TNF-alpha) effectively targets tumor vasculature, enhancing chemotherapy delivery. This modified TNF-alpha shows reduced side effects compared to the wild-type, offering a safer systemic antitumor approach.

Area of Science:

  • Oncology
  • Biotechnology
  • Pharmacology

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) has potential for selective tumor endothelial cell destruction and enhancing vascular permeability for chemotherapy.
  • Systemic clinical application of TNF-alpha is limited by severe toxic side effects.

Purpose of the Study:

  • To evaluate the efficacy and safety of PEGylated TNF-alpha (PEG-TNF-alpha) as a systemic antitumor agent and selective enhancer of tumor vascular permeability.

Main Methods:

  • Comparison of PEG-TNF-alpha and wild-type TNF-alpha in S-180 tumor models.
  • Assessment of hemorrhagic necrosis, side effects, and tumor vascular permeability changes.
  • Evaluation of PEG accumulation in tumor and normal tissues.

Main Results:

  • PEG-TNF-alpha (1000 JRU) induced significant hemorrhagic necrosis in S-180 tumors with no observed side effects.
  • Wild-type TNF-alpha (10,000 JRU) showed minimal necrosis and severe side effects.
  • PEG-TNF-alpha selectively enhanced tumor vascular permeability within 1-2 hours post-injection without affecting normal tissues.

Conclusions:

  • PEG-TNF-alpha demonstrates a favorable safety profile and efficacy in selectively targeting tumor vasculature.
  • PEG-TNF-alpha is a promising agent for enhancing the accumulation of chemotherapeutic agents in tumors.

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