Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.

The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect.

The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting.

The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo

Basal ganglia and cerebellar loops: motor and cognitive circuits.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.20063

Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages.

Enhanced vascular permeability in tumor tissue has profound pathological consequences in tumor biology. However, details of the mechanism involved are not clear. The present work on tumor vascular permeability has led to the following three findings. (i) Ascitic tumor fluid contained kinin (about 1-40 ng/ml), which is known to enhance vascular permeability and induce pain in vivo. (ii) Kinin is generated via the kallikrein-dependent cascade in the ascitic tumor fluid. By blocking this kinin-generating cascade with Kunitz-type soybean trypsin inhibitor the formation of ascites was suppressed. (iii) Blocking of kinin-degrading enzymes (kininases I and II) by an appropriate kininase inhibitor (e.g., captopril) may result in increased permeability, leading to accumulation of the ascitic fluid. This phenomenon was verified by an about 1.2-1.5 fold increase in leakage of 51Cr-labeled bovine serum albumin into the ascites when kininase inhibitors had been administered orally 30 min before intravenous administration of the bovine serum albumin.

/pdf/involvement-of-the-kinin-generating-cascade-in-enhanced-i9rm5rl6ac.pdf

Involvement of the kinin-generating cascade in enhanced vascular permeability in tumor tissue

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2003.50259

Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages.

A serratial protease with an apparent molecular weight of 56,000 (56K protease), which had been purified from the culture supernatant of a strain of Serratia marcescens isolated from a corneal lesion of a human eye [Matsumoto, K. et al. (1984) J. Bacteriol. 157, 225-232], greatly enhanced vascular permeability when injected into guinea pig skin. The 56K protease, which requires zinc ion for activity, was found to possess plasma kallikrein-like properties in vitro as judged by (i) preferential amidolysis of carbobenzoxy-Phe-Arg-4-methylcoumaryl-7-amide and Pro-Phe-Arg-4-methylcoumaryl-7-amide, which are known substrates for plasma kallikrein; (ii) release of kinin from high-molecular-weight kininogen; and (iii) prompt activation of Hageman factor followed by generation of kallikrein from plasma prekallikrein. These results suggest that the 56K protease enhances vascular permeability through activation of a Hageman factor-kallikrein-kinin pathway in vivo, and this molecular process appears to be a rational mechanism of enhancement of permeability and serratial pathogenesis.

Pathogenesis of Serratial Infection: Activation of the Hageman Factor-Prekallikrein Cascade by Serratial Protease

The medial dorsal nucleus is one of the thalamic relays of the cerebellocerebral responses to the frontal association cortex in the monkey: horseradish peroxidase and fluorescent dye double staining study

Tetsuro Yamamoto

Papers

Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages.

Involvement of the kinin-generating cascade in enhanced vascular permeability in tumor tissue

Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages.

Pathogenesis of Serratial Infection: Activation of the Hageman Factor-Prekallikrein Cascade by Serratial Protease

The medial dorsal nucleus is one of the thalamic relays of the cerebellocerebral responses to the frontal association cortex in the monkey: horseradish peroxidase and fluorescent dye double staining study