PMID- 2946403 OWN - NLM STAT- MEDLINE DCOM- 19861224 LR - 20220410 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 46 IP - 12 Pt 1 DP - 1986 Dec TI - A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. PG - 6387-92 AB - We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis. FAU - Matsumura, Y AU - Matsumura Y FAU - Maeda, H AU - Maeda H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Albumins) RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Antineoplastic Agents) RN - 0 (Furans) RN - 0 (Maleic Anhydrides) RN - 0 (Polystyrenes) RN - 0 (Proteins) RN - 0 (poly(maleic acid-styrene)neocarzinostatin) RN - 45PG892GO1 (Evans Blue) RN - 9014-02-2 (Zinostatin) SB - IM MH - Albumins/metabolism MH - Animals MH - Antibiotics, Antineoplastic/*metabolism MH - Antineoplastic Agents/*metabolism/therapeutic use MH - Evans Blue/metabolism MH - Furans/*metabolism MH - Maleic Anhydrides/*metabolism/therapeutic use MH - Metabolic Clearance Rate MH - Mice MH - Molecular Weight MH - Neoplasms, Experimental/drug therapy/*metabolism MH - Polystyrenes/*metabolism/therapeutic use MH - Proteins/*metabolism MH - Zinostatin/analogs & derivatives/*metabolism/therapeutic use EDAT- 1986/12/01 00:00 MHDA- 1986/12/01 00:01 CRDT- 1986/12/01 00:00 PHST- 1986/12/01 00:00 [pubmed] PHST- 1986/12/01 00:01 [medline] PHST- 1986/12/01 00:00 [entrez] PST - ppublish SO - Cancer Res. 1986 Dec;46(12 Pt 1):6387-92.