Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical application of macromolecular Gd(III) complexes as MRI contrast agents is impeded by their slow excretion and potential toxicity due to the release of Gd(III) ions caused by the metabolism of the agents. A polymer Gd(III) chelate conjugate with a cleavable spacer has been designed to solve this problem. Poly(l-glutamic acid)-cystamine-[Gd(III)-DOTA] was prepared by the conjugation of DOTA to PGA (MW = 50,000) via cystamine, a cleavable disulfide spacer, followed by the complexation with GdCl(3). A Gd(III) DOTA chelate derivative was readily released from the polymer conjugate in the incubation with cysteine, an endogenous plasma thiol. The conjugate produced significant MRI blood pool contrast enhancement in nude mice bearing OVCAR-3 human ovarian carcinoma xenographs. Less significant contrast enhancement was observed for a small molecular contrast agent, Gd(DTPA-BMA). The pharmacokinetic MRI study showed that the Gd(III) chelate from the conjugate accumulated in the urinary bladder in a similar kinetic pattern to Gd(DTPA-BMA), suggesting that the chelate was released by the endogenous thiols and excreted through renal filtration. The preliminary results suggest that this novel design has a great potential to solve the safety problem of macromolecular MRI contrast agents.
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PMID:Poly(l-glutamic acid) Gd(III)-DOTA conjugate with a degradable spacer for magnetic resonance imaging. 1286 23

The aim of this study was to elucidate effects of Delta(7)-prostaglandin A(1) methyl ester (Delta(7)-PGA(1)) alone, and Delta 7-PGA(1) emulsified in lecithin oil (lipo Delta(7)-PGA(1)) alone, and their combinations with cis-diamminedichloroplatinum(II) (CDDP) on the tumor growth of an ovarian carcinoma cell line resistant to CDDP (2008/c13) and the parental cell line (2008) in vitro and in scid mice. With regard to concentration of CDDP required for 50% inhibition of cell proliferation in vitro (IC50), 2008/c13 was 5.76-fold higher resistant to CDDP than 2008, while the degree of resistance of 2008/c13 to Delta(7)-PGA(1) was less than a half of that to CDDP. When 2008 cells were heterotransplanted s.c. into the right flank of scid mice, the tumor growth was not inhibited by treatment with CDDP alone, Delta(7)-PGA(1) alone or lipo Delta(7)-PGA(1) alone. However, when CDDP was combined with lipo Delta(7)-PGA(1) (but not Delta(7)-PGA(1)), the tumor growth was significantly (P<0.05) inhibited on days 35 and 42 after tumor inoculation, compared to untreated and all alone treated groups. When CDDP-resistant 2008/c13 cells were inoculated s.c. into the right flank of scid mice, CDDP alone treatment resulted in a significant (P<0.05) inhibition of the tumor growth, suggesting that the sensitivity of this tumor to CDDP is rather higher than 2008-tumor of which growth was not inhibited by CDDP alone. A significant decrease of body weight was observed only when CDDP was combined with lipo Delta(7)-PGA(1) in scid mice bearing 2008 cells, as confirmed by monitoring hematocrit and body weight. However, these mice had no serious weight loss leading to death. These results suggest that combination of CDDP and lipo Delta(7)-PGA(1) may be effective for treatment of patients with ovarian carcinoma clinically resistant or insensitive to CDDP.
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PMID:Combined effects of Delta(7)-prostaglandin A(1) and lipo Delta(7)-prostaglandin A(1) to cis-diamminedichloroplatinum(II) on tumor growth in scid mice bearing 2008 and 2008/c13 cells. 2159 14