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001-es BibID:BIBFORM015979
Első szerző:Papadia, Andrea
Cím:Experimental therapy of ES-2 human platinum resistant ovarian cancer with growth hormone-releasing hormone antagonist JMR-132 or with targeted cytotoxic analog somatostatin AN-162 / A. Papadia, A. Schally, S. Seitz, S. Buchholz, F. Rick, L. Szalontay, G. Halmos, A. Treszl, J. A. Lucci
Dátum:2004
ISSN:0090-8258
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
Megjelenés:Gynecologic Oncology. - 112 : 2 (2004), p. S128-S129. -
További szerzők:Schally, Andrew Victor Seitz, Stephan Buchholz, Stefan Rick Ferenc G. Szalontay Luca Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Treszl Andrea (1974-) (molekuláris biológus) Lucci III, J. A.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:BIBFORM004789
Első szerző:Papadia, Andrea
Cím:Experimental therapy of ES-2 human platinum resistant ovarian cancer with targeted cytotoxic somatostatin and LHRH analogues / A. Papadia, A. V. Schally, S. Seitz, S. Buchholz, A. Treszl, L. Szalontay, G. Halmos, J. A. Lucci III
Dátum:2008
Megjegyzések:New methods are needed for treatment of platinum resistant ovarian cancers. It has been shown that ovarian cancers express receptors for LHRH and somatostatin. The aim of the study is to test targeted cytotoxic analogue of somatostatin AN-162 [AEZS-124] and of LHRH AN-152 [AEZS-108] consisting of Doxorubicin (DOX) conjugated respectively to somatostatin octapeptide RC-121 and to [D-Lys6] LHRH analogue, which act as a carrier. Methods. The expression of mRNA for somatostatin and LHRH receptors in ES-2 platinum resistant human ovarian cancer cell line was investigated by RT-PCR. Somatostatin and LHRH receptor proteins were measured by ligand competitive assays. Nude mice bearing ES-2 tumors were randomized into five groups, which received weekly intravenous injections of AN-162, DOX, somatostatin analogue (RC-160), combination of RC-160 and DOX or solvent, respectively. Mean tumor volumes measured weekly were compared with ANOVA test. Subsequently, the effect of AN-162 and AN-152 versus DOX was tested in a similar model. The doses of AN-162, AN-152 and RC-160 were equivalent to 1.45 mg/kg DOX (2.5 ?mol/kg). Results. ES-2 expressed mRNA for sstr1, sstr2, sstr3, sstr4 and also for LHRH receptors. High affinity binding sites for LHRH (Kd = 3.84 nM; Bmax = 287.9 fmol/mg protein) and somatostatin (Kd = 6.71 nM; Bmax = 375.9 fmol/mg protein) were demonstrated in ES-2 cancer samples. Tumor volume of mice treated with AN-162 was significantly smaller than that of the other groups (p < 0.001). Tumor volumes of mice treated with RC-160 and with the combination of RC160 and DOX were also smaller than those of the control and DOX groups (p < 0.001). Final tumor growth expressed as percent of the starting volume was as follows: 1991% ? 19.4% for control, 1469% ? 29.7% for DOX, 1268% ? 23.5% for the combination of RC-160 and DOX, 1077% ? 13% for RC-160, and 813% ? 21.6% for AN-162. Tumor growth inhibition was similar with AN-162 and AN-152 and greater as compared to DOX or control (P < 0.005). Conclusion. Targeted somatostatin and LHRH cytotoxic analogues AN-162 and AN-152 produce a greater inhibition of tumor growth than DOX in somatostatin and LHRH receptor positive platinum resistant human ovarian cancer. These findings support the concept of targeted chemotherapy based on cytotoxic peptide analogues for the treatment of gynecological cancers and other cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idézhető absztrakt
Megjelenés:Gynecologic Oncology. - 111 : 2 (2008), p. 376. -
További szerzők:Schally, Andrew Victor Seitz, S. Buchholz, Stefan Treszl Andrea (1974-) (molekuláris biológus) Szalontay Luca Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Lucci III, J. A.
Internet cím:DOI
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