PMID- 12639809 OWN - NLM STAT- MEDLINE DCOM- 20031217 LR - 20220408 IS - 1567-5769 (Print) IS - 1567-5769 (Linking) VI - 3 IP - 3 DP - 2003 Mar TI - Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. PG - 319-28 AB - Most solid tumors are known to exhibit highly enhanced vascular permeability, similar to or more than the inflammatory tissues. Common denominators affecting both cancer and inflammatory lesions are now well known: bradykinin (BK), nitric oxide (NO), peroxynitrite (ONOO(-)), prostaglandins (PGs), collagenases or matrix metalloproteinases (MMPs) and others. Incidentally, enzymes involved in these mediator syntheses are upregulated or activated. Initially described vascular permeability factor (VPF) (proteinaceous) was later identified to be the same as vascular endothelial growth factor (VEGF), which promotes angiogenesis of cancer tissues as well. These mediators cross-talk or co-upregulate each other, such as BK-NO-PGs system. Therefore, vascular permeability observed in solid tumor may reflect the other side of the coin (angiogenesis). The vascular permeability and accumulation of plasma components in the interstitium described here is applicable for predominantly macromolecules (molecular weight, Mw>45 kDa), but not for low molecular compounds as most anticancer agents are. Macromolecular compounds (e.g., albumin, transferrin) or many biocompatible water-soluble polymers show this effect. Furthermore, they are not cleared rapidly from the sites of lesion (cancer/inflammatory tissue), thus, remain for prolonged time, usually for more than a few days. This phenomenon of "enhanced permeability and retention effect" observed in cancer tissue for macromolecules and lipids is coined "EPR effect", which is now widely accepted as a gold standard for anticancer drug designing to seek more cancer-selective targeting using macromolecular drugs. Consequently, drastic reduction of the systemic side effect is observed, while the macromolecular drugs will continuously exert antitumor activity. Other advantages of macromolecular drugs are also discussed. FAU - Maeda, Hiroshi AU - Maeda H AD - Department of Microbiology, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto 860-0811, Japan. msmaedah@gpo.kumamoto-u.ac.jp FAU - Fang, Jun AU - Fang J FAU - Inutsuka, Takao AU - Inutsuka T FAU - Kitamoto, Yasunori AU - Kitamoto Y LA - eng PT - Journal Article PT - Review PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Antineoplastic Agents) RN - 0 (Inflammation Mediators) SB - IM MH - Animals MH - Antineoplastic Agents/chemistry/pharmacology MH - Capillary Permeability/*physiology MH - Humans MH - Inflammation Mediators/physiology MH - Neoplasms/*blood supply MH - Neovascularization, Pathologic/pathology/prevention & control MH - Regional Blood Flow/physiology RF - 59 EDAT- 2003/03/18 04:00 MHDA- 2003/12/18 05:00 CRDT- 2003/03/18 04:00 PHST- 2003/03/18 04:00 [pubmed] PHST- 2003/12/18 05:00 [medline] PHST- 2003/03/18 04:00 [entrez] AID - S1567-5769(02)00271-0 [pii] AID - 10.1016/S1567-5769(02)00271-0 [doi] PST - ppublish SO - Int Immunopharmacol. 2003 Mar;3(3):319-28. doi: 10.1016/S1567-5769(02)00271-0.