Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CPT-11-resistant human gastric and colonic xenograft lines were established by direct intratumoral injection of CPT-11 into subcutaneous SC-1-NU and CC-2-NU tumors in nude mice once a week for 10 months. The resistance of these xenograft lines to CPT-11 was confirmed by growth inhibition rate, to be 36.3% and 45.4%, respectively, compared to each parent cell line. DNA topoisomerase I activity of the nuclear extracts of SC-1-NU/CPT-11 and CC-2-NU/CPT-11, as assayed by relaxation of supercoiled DNA Col-E1, was significantly less than those of the parent lines. The cellular levels of topoisomerase I in those resistant lines measured by Western blot analysis were 0.57- and 0.79-fold lower than those of the parental lines, respectively. However, the activity of DNA topoisomerase II of those resistant cell lines assayed by decatenation of kinetoplast DNA was higher than that of the parental lines and the cellular levels of topoisomerase II in the resistant lines measured by Western blot analysis were 10.8- and 8.1-fold higher than those of the parent lines. Intracellular accumulation of CPT-11 in CPT-11-resistant tumors was not changed as compared to that of the parental lines, but hydrolysis of CPT-11 to more active SN-38 was reduced in the resistant tumors.
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PMID:Establishment and characterization of human gastric and colonic xenograft lines resistant to CPT-11 (a new derivative of camptothecin). 777 52

The human monoclonal antibody SC-1 was isolated from a patient with a diffuse-type adenocarcinoma of the stomach using somatic cell hybridization. The immunoglobulin (Ig)M antibody reacts specifically with diffuse- (70%) and intestinal-type (25%) gastric adenocarcinoma and induces apoptosis in vitro and in vivo. When used in clinical trials with stomach carcinoma patients, significant apoptotic and regressive effects in primary tumors have been observed with the antibody SC-1. The SC-1 receptor is a new 82 kd membrane-bound isoform of glycosylphosphatidylinositol (GPI)-linked CD55 (decay-accelerating factor, DAF). CD55 is known to protect cells from lysis through autologous complement and is coexpressed with the ubiquitously distributed 70 kd isoform. The SC-1-specific CD55 isoform is up-regulated shortly after antibody binding, followed by an internalization of the antibody/receptor-complex, whereas the membranous expression of wild-type CD55 remains unchanged. The apoptotic process is marked by cleavage of cytokeratin 18, indicating the involvement of caspase-6 in the apoptotic process. In contrast to other apoptotic pathways, a cleavage of poly(ADP-ribose)polymerase (PARP) is not observed. The expression of the cell-cycle regulator c-myc becomes up-regulated, whereas expression of topoisomerase IIalpha is down-regulated. Induction of apoptosis leads to an increase in the internal Ca(2+) concentration, which is not necessary for the apoptotic process but for the transport of newly synthesized SC-1-specific CD55 isoform to the membrane.
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PMID:Regulation of the new coexpressed CD55 (decay-accelerating factor) receptor on stomach carcinoma cells involved in antibody SC-1-induced apoptosis. 1170 63