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001-es BibID:BIBFORM002233
035-os BibID:WOS:000242995600010
Első szerző:Goda Katalin (biofizikus)
Cím:Complete inhibition of P-glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody / Katalin Goda, Ferenc Fenyvesi, Zsolt Bacsó, Henrietta Nagy, Teréz Márián, Attila Megyeri, Zoltán Krasznai, István Juhász, Miklós Vecsernyés, Gábor Szabó
Dátum:2007
Megjegyzések:P-glycoprotein (Pgp) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance. The conformation-sensitive UIC2 monoclonal antibody potentially inhibits Pgp-mediated substrate transport. However, this inhibition is usually partial, and its extent is variable because UIC2 binds only to 10 to 40% Pgp present in the cell membrane. The rest of the Pgp molecules become recognized by this antibody only in the presence of certain substrates or modulators, including vinblastine, cyclosporine A (CsA), and SDZ PSC 833 (valspodar). Simultaneous application of any of these modulators and UIC2, followed by the removal of the modulator, results in a completely restored steady-state accumulation of various Pgp substrates (calcein-AM, daunorubicin, and 99mTc-hexakis-2- methoxybutylisonitrile), indicating near 100% inhibition of pump activity. Remarkably, the inhibitory binding of the antibody is brought about by coincubation with concentrations of CsA or SDZ PSC 833 20 times lower than what is necessary for Pgp inhibition when the modulators are applied alone. The feasibility of such a combinative treatment for in vivo multidrug resistance reversal was substantiated by the dramatic increase of daunorubicin accumulation in xenotransplanted Pgp tumors in response to a combined treatment with UIC2 and CsA, both administered at doses ineffective when applied alone. These observations establish the combined application of a class of modulators used at low concentrations and of the UIC2 antibody as a novel, specific, and effective way of blocking Pgp function in vivo.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
UIC2 monoclonal antibody
P-glycoprotein
Megjelenés:The Journal of Pharmacology and Experimental Therapeutics 320 : 1 (2007), p. 81-88. -
További szerzők:Fenyvesi Ferenc (1977-) (gyógyszerész, gyógyszertechnológus) Bacsó Zsolt (1963-) (biofizikus) Nagy Henrietta Márián Teréz (1950-) (radiobiológus) Megyeri Attila (1968-) (orvos) Krasznai Zoltán (1950-) (biofizikus) Juhász István (1956-) (bőrgyógyász, bőrsebész, kozmetológus, klinikai onkológus) Vecsernyés Miklós (1959-) (gyógyszertechnológus, endokrinológus) Szabó Gábor (1980-) (orvos) jr
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
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2.

001-es BibID:BIBFORM040018
Első szerző:Nagy Henrietta
Cím:P-Glycoprotein conformational changes detected by antibody competition / Nagy Henrietta, Goda Katalin, Arceci Robert, Cianfriglia Maurizio, Mechetner Eugene, Szabó Gábor jr.
Dátum:2001
ISSN:0014-2956
Megjegyzések:Conformational changes accompanying P-glycoprotein (Pgp) mediated drug transport are reflected by changes in the avidity of certain monoclonal antibodies (mAbs). More of the UIC2 mAb binds to Pgp-expressing cells in the presence of substrates or modulators [Mechetner, E.B., Schott, B., Morse, S.B., Stein, W., Druley, T., Dvis, K.A., Tsuruo, T. & Roninson, I.B. (1997) Proc. Natl Acad. Sci. USA 94, 12908-12913], while the binding of other mAbs (e.g. MM12.10, MRK16, 4E3) is not conformation sensitive. Pre-staining of Pgp+ cells with UIC2 decreased the subsequent binding of MM12.10 mAb by about 30-40%, suggesting that there are Pgp molecules available for both UIC2 and MM12.10, and others accessible only for MM12.10. In the presence of certain substrates/modulators such as vinblastin, cyclosporin A or valinomycin, the MM12.10 reactivity was completely abolished by preincubation with UIC2. However, verapamil, Tween-80 and nifedipine did not influence the ratio of bound mAbs significantly. This is the first assay to our knowledge, sharply distinguishing two classes of modulators. The conformational changes accompanying the mAb competition phenomenon appear to be closely related, though not identical to those accompanying the UIC2-shift, as suggested by the simultaneous assessment of the two phenomena.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
3T3 Cells
Animal
Antibiotics
Antibiotics,Peptide
Antibodies
Antibodies,Monoclonal
Antineoplastic Agents
Antineoplastic Agents,Phytogenic
Binding,Competitive
Biophysics
Calcium
Calcium Channel Blockers
Cells
chemistry
Cyclosporine
Drug Resistance,Neoplasm
Enzyme Inhibitors
Flow Cytometry
Human
Hungary
metabolism
Mice
Nifedipine
P-Glycoprotein
pharmacology
Polysorbates
Protein Binding
Protein Conformation
Substrate Specificity
Support,Non-U.S.Gov't
Tumor Cells,Cultured
Valinomycin
Verapamil
Vinblastine
Megjelenés:European Journal Of Biochemistry. - 268 : 8 (2001), p. 2416-2420. -
További szerzők:Goda Katalin (1969-) (biofizikus) Arceci, Robert Cianfriglia, Maurizio Mechetner, Eugene Szabó Gábor (1980-) (orvos) jr
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DOI
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