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1.

001-es BibID:BIBFORM019785
Első szerző:Hohla, Florian
Cím:Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells / Hohla Florian, Buchholz Stefan, Schally Andrew V., Krishan Awtar, Rick Ferenc G., Szalontay Luca, Papadia Andrea, Halmos Gabor, Koster Frank, Aigner Elmar, Datz Christian, Seitz Stephan
Dátum:2010
ISSN:0304-3835
Megjegyzések:The effect of the targeted cytotoxic somatostatin (SST) analog AN-162, consisting of doxorubicin (DOX) conjugated to SST carrier RC-121, was investigated on the growth of human colorectal cancer (CRC) cell lines HT-29, HCT-15, and HCT-116 and a DOX-resistant mouse leukemia cell line P388/R84. mRNA for SST-receptors and high affinity binding sites for SST were detected in all CRC cell lines and in P388/R84 cells. In contrast to DOX alone, AN-162 blocked HCT-116 cells and P388/R84 cells in S/G2 phase and increased the number of apoptotic cells. In vivo, AN-162 reduced the volume of CRC xenografts more effectively than its unconjugated components. Our results suggest that AN-162 inhibits growth of experimental CRC more effectively than DOX and increases sensitivity of DOX resistant human leukemia cells.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Cancer Letters. - 294 : 1 (2010), p. 35-42. -
További szerzők:Buchholz, Stefan Schally, Andrew Victor Krishan, Awtar Rick Ferenc G. Szalontay Luca Papadia, Andrea Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Koster, Frank Aigner, Elmar Datz, Christian Seitz, Stephan
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2.

001-es BibID:BIBFORM030454
Első szerző:Klukovits Anna
Cím:Novel antagonists of growth hormone-releasing hormone inhibit growth and vascularization of human experimental ovarian cancers / Anna Klukovits, Andrew V. Schally, Luca Szalontay, Irving Vidaurre, Andrea Papadia, Marta Zarandi, Jozsef L. Varga, Norman L. Block, Gabor Halmos
Dátum:2012
ISSN:0008-543X
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) inhibit the proliferation of various human cancer cell lines and experimental tumors by mechanisms that include direct action on GHRH receptors in cancer cells. METHODS: In this study, the effects of newly synthesized GHRH antagonists, MIA-313, MIA-602, MIA-604, and MIA-610, were investigated in 2 human ovarian epithelial adenocarcinoma cell lines, OVCAR-3 and SKOV-3, in vitro and in vivo. The expression of receptors for GHRH was demonstrated by Western blot analysis and ligand competition methods in the OVCAR-3 and SKOV-3 cell lines and in tumors from those cells grown in athymic nude mice. The effects of GHRH antagonists on the secretion of vascular endothelial growth factor (VEGF) by OVCAR-3 cells and on the vascularization of OVCAR-3 xenografts also were evaluated. RESULTS: Both the pituitary and the splice variant type 1 (SV1) GHRH receptors were detected in the 2 cell lines and in tumor xenografts, and SV1 was expressed at higher levels. Cell viability assays revealed the antiproliferative effect of all GHRH antagonists that were. Maximal tumor growth inhibition was approximately 75% in both models. MIA-313 and MIA-602 decreased VEGF secretion of OVCAR-3 cells, as measured by enzyme-linked immunosorbent assay, and reduced tumor vascularization in a Matrigel plug assay, but caused no change in the expression of VEGF or VEGF receptor in the terminal ileum of mice with OVCAR-3 tumors. CONCLUSIONS: Results from the current study indicated that a he novel approach based on GHRH antagonists may offer more effective therapeutic alternatives for patients with advanced ovarian cancer and who do not tolerate conventional anti-VEGF therapy.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Molekulatudomány
Megjelenés:Cancer. - 118 : 3 (2012), p. 670-680. -
További szerzők:Schally, Andrew Victor Szalontay Luca Vidaurre, Irving Papadia, Andrea Zarándi Márta Varga József L. Block, Norman L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Peptid hormon és növekedési faktor receptorok mint molekuláris célpontok a humán rosszindulatú daganatok diagnosztikájában és terápiájában
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3.

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.
Dátum:2011
ISSN:0018-5043
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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4.

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.
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5.

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.
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6.

001-es BibID:BIBFORM011473
Első szerző:Seitz, Stephan
Cím:Preclinical evaluation of properties of a new targeted cytotoxic somatostatin analog, AN-162 (AEZS-124), and its effects on tumor growth inhibition / Seitz S., Schally A. V., Treszl A., Papadia A., Rick F., Szalontay L., Szepeshazi K., Ortmann O., Halmos G., Hohla F., Buchholz S.
Dátum:2009
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Anti-Cancer Drugs. - 20 : 7 (2009), p. 553-558. -
További szerzők:Schally, Andrew Victor Treszl Andrea (1974-) (molekuláris biológus) Papadia, Andrea Rick Ferenc G. Szalontay Luca Szepesházi Károly Ortmann, Olaf Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Hohla, Florian Buchholz, Stefan
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