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001-es BibID:BIBFORM040825
Első szerző:Papadia, Andrea
Cím:Growth Hormone-Releasing Hormone Antagonists Inhibit Growth of Human Ovarian Cancer / Papadia, A., Schally, A., Halmos, G., Varga, J., Seitz, S., Buchholz, S., Rick, F., Zarandi, M., Bellyei, S., Treszl, A., Szalontay, L., Lucci, J. A.
Megjegyzések:Epithelial ovarian carcinoma is the leading cause of cancer-related deaths among women with gynecologic malignancies. Antagonists of the growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of various cancers through endocrine, autocrine, and paracrine mechanisms. In this study, we have investigated the effects of GHRH antagonists (GHRHa) in ES-2 human clear cell ovarian cancer and in UCI-107 human serous ovarian cancer in vitro and in vivo. We evaluated the expression of mRNA for GHRH receptor, the binding to GHRH receptors, in specimens of ES-2 ovarian cancer. We evaluated also the in vitro effects of GHRHa on ES-2 cells and the in vivo effect of 2 different GHRHa on ES-2 and UCI-107 tumors. Nude mice bearing xenografts on ES-2 and UCI-107 ovarian cancer were treated with JMR-132 and MZ-J-7-118, respectively. Tumor growth was compared to control. ES-2 cells expressed mRNA for the functional splice variant SV1 of the GHRH receptor. JMR-132 inhibited cell proliferation in vitro by 42% and 18% at 10 and 1 gammaM concentration, respectively. Specific high affinity receptors for GHRH were detected in ES-2 cancer samples. In vivo daily subcutaneous injections of GHRHa significantly reduced tumor growth compared to a control group in both animal models. Our results indicate that GHRHa such as JMR-132 and MZ-J-7-118 can inhibit the growth of human ovarian cancer. The efficacy of GHRHa in ovarian cancer should be assessed in clinical trials.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Hormone And Metabolic Research. - 43 : 11 (2011), p. 816-820. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Varga J. (orvos) Seitz, S. Buchholz, Stefan Rick Ferenc G. Zarándi Márta Bellyei Szabolcs Treszl Andrea (1974-) (molekuláris biológus) Szalontay Luca Lucci III, J. A.
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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
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.
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