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1.

001-es BibID:BIBFORM049347
Első szerző:Cai, Ren-Zhi
Cím:Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities / Renzhi Cai, Andrew V. Schally, Tengjiao Cui, Luca Szalontay, Gabor Halmos, Wei Sha, Magdolna Kovacs, Miklos Jaszberenyi, Jinlin He, Ferenc G. Rick, Petra Popovics, Rosemeire Kanashiro-Takeuchi, Joshua M. Hare, Norman L. Block, Marta Zarandi
Dátum:2013
ISSN:0196-9781
Megjegyzések:AbstractIn view of the recent findings of stimulatory effects of GHRH analogs, JI-34, JI-36 and JI-38, on cardiomyocytes, pancreatic islets and wound healing, three series of new analogs of GHRH(1-29) have been synthesized and evaluated biologically in an endeavor to produce more potent compounds. "Agmatine analogs", MR-356 (N-Me-Tyr1-JI-38), MR-361(N-Me-Tyr1, D-Ala2-JI-38) and MR-367(N-Me-Tyr1, D-Ala2, Asn8-JI-38), in which Dat in JI-38 is replaced by N-Me-Tyr1, showed improved relative potencies on GH release upon subcutaneous administration in vivo and binding in vitro. Modification with N-Me-Tyr1 and Arg29-NHCH3 as in MR-403 (N-Me-Tyr1, D-Ala2, Arg29-NHCH3-JI-38), MR-406 (N-Me-Tyr1, Arg29-NHCH3-JI-38) and MR-409 (N-Me-Tyr1, D-Ala2, Asn8, Arg29-NHCH3-JI-38), and MR-410 (N-Me-Tyr1, D-Ala2, Thr8, Arg29-NHCH3-JI-38) resulted in dramatically increased endocrine activities. These appear to be the most potent GHRH agonistic analogs so far developed. Analogs with Apa30-NH2 such as MR-326 (N-Me-Tyr1, D-Ala2, Arg29, Apa30-NH2-JI-38), and with Gab30-NH2, as MR-502 (D-Ala2, 5F-Phe6, Ser28, Arg29,Gab30-NH2-JI-38) also exhibited much higher potency than JI-38 upon i.v. administration. The relationship between the GH-releasing potency and the analog structure is discussed. Fourteen GHRH agonists with the highest endocrine potencies were subjected to cardiologic tests. MR-409 and MR-356 exhibited higher potency than JI-38 in activating myocardial repair in rats with induced myocardial infarction. As the previous class of analogs, exemplified by JI-38, had shown promising results in multiple fields including cardiology, diabetes and wound healing, our new, more potent, GHRH agonists should manifest additional efficacy for possible medical applications.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
5-aminopentanoyl
Abu
Agm
Apa
Cardioprotection
Dat
EF
Fpa5
GH
GH-releasing hormone
GHRH
Gab
IGF
MI
MeCN
N-Me-Tyr
N-methyl-tyrosine
PKA
PKC
PLC
TOF
acetonitrile
agmatine
des-amino-tyrosine
ejection fraction
gamma-amino-butanoyl
growth hormone
hGHRH agonist
hGHRH(1-29)
human
i.v.
insulin-like growth factor
intravenous, myocardial infarction
pentafluoro-Phe, phospholipase C
protein kinase A
protein kinase C
s.c.
s.c. administration
subcutaneous
time-of-flight
Megjelenés:Peptides. - 52C (2013), p. 104-112. -
További szerzők:Schally, Andrew Victor Cui, Tengjiao Szalontay Luca Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Sha, Wei Kovács Magdolna Jászberényi Miklós He, Jinlin Rick Ferenc G. Popovics Petra Kanashiro-Takeuchi, Rosemeire Hare, Joshua M. Block, Norman L. Zarándi Márta
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0025
TÁMOP
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2.

001-es BibID:BIBFORM033578
035-os BibID:PMID:15784701 WOS:000229351000068
Első szerző:Engel, Jörg B.
Cím:Inhibition of growth of experimental human endometrial cancer by an antagonist of growth hormone-releasing hormone / Jörg B. Engel, Gunhild Keller, Andrew V. Schally, Gabor L. Toller, Kate Groot, Alexandre Havt, Patricia Armatis, Marta Zarandi, Jozsef L. Varga, Gabor Halmos
Dátum:2005
ISSN:0021-972X
Megjegyzések:Antagonists of GHRH are being developed for the treatment of various cancers. In this study we investigated in vivo and in vitro the effects of the GHRH antagonist MZ-J-7-118 and its mechanism of action in HEC-1A human endometrial cancer. Treatment of nude mice bearing HEC-1A xenografts with 10 mug/d MZ-J-7-118 for 6 wk significantly inhibited the volume of HEC-1A tumors by 43%, tumor weight by 40% compared with controls and prolonged the tumor doubling time from 18.7 +/- 1.4 to 25.4 +/- 3.8 d. Administration of 20 mug MZ-J-7-118, sc, twice a day significantly (P < 0.05) decreased HEC-1A growth, as evidenced by a 57.9% decrease in tumor volume, a 50.7% reduction in tumor weight, and the extension of tumor doubling time from 17.5 +/- 2.8 to 36.4 +/- 6.5 d. Therapy with GHRH antagonists significantly decreased serum IGF-I levels in experiment 1, and significantly increased tumoral IGF-I levels in experiment 2 in treated mice. Levels of IGF-II and vascular endothelial growth factor-A in tumors were not changed. Specific high affinity binding sites for GHRH were found on HEC-1A tumor membranes using ligand competition assays with (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-118 displaced radiolabeled JV-1-42 with an IC(50) of 0.13 +/- 0.04 nm. The expression of mRNA for GHRH and splice variants of the GHRH receptor in HEC-1A tumors was demonstrated by real-time RT-PCR analysis. HEC-1A cells cultured in vitro secreted GHRH into the medium. The GHRH antagonist MZ-J-7-118 inhibited the growth of HEC-1A cells in vitro. Our results indicate that GHRH antagonists can reduce the growth of human endometrial cancer and could be used as an alternative adjuvant therapy for the management of endometrial cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal Of Clinical Endocrinology & Metabolism. - 90 : 6 (2005), p. 3614-3621. -
További szerzők:Keller, Gunhild Schally, Andrew Victor Toller Gábor L. Groot, Kate Havt, Alexandre Armatis, Patricia Zarándi Márta Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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3.

001-es BibID:BIBFORM033557
035-os BibID:WOS:000233762000030
Első szerző:Havt, Alexandre
Cím:The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues / Alexandre Havt, Andrew V. Schally, Gabor Halmos, Jozsef L. Varga, Gabor L. Toller, Judit E. Horvath, Karoly Szepeshazi, Frank Köster, Kevin Kovitz, Kate Groot, Marta Zarandi, Celia A. Kanashiro
Dátum:2005
ISSN:0027-8424
Megjegyzések:Various attempts to detect human pituitary growth hormone-releasing hormone receptor (pGHRH-R) in neoplastic extrapituitary tissues have thus far failed. Recently, four splice variants (SVs) of GHRH-R have been described, of which SV1 has the highest structural homology to pGHRH-R and likely plays a role in tumor growth. The aim of this study was to reinvestigate whether human tumors and normal human extrapituitary tissues express the pGHRH-R and to corroborate our previous findings on its SVs. Thus, we developed a real-time PCR method for the detection of the mRNA for the pGHRH-R, its SVs, and the GHRH peptide. Using real-time PCR, Western blotting, and radioligand-binding assays, we detected the mRNA for pGHRH-R and pGHRH-R protein in various human cancer cell lines grown in nude mice and in surgical specimens of human lung cancers. The expression of mRNA for SVs of pGHRH-R and GHRH was likewise found in xenografts of human non-Hodgkin's lymphomas, pancreatic cancer, glioblastoma, small-cell lung carcinomas, and in human nonmalignant prostate, liver, lung, kidney, and pituitary. Western blots showed that these normal and malignant human tissues contain SV1 protein and immunoreactive GHRH. Our results demonstrate that some normal human tissues and tumors express mRNA and protein for the pGHRH-R and its splice variants. These findings confirm and extend the concept that GHRH and its receptors play an important role in the pathophysiology of human cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States Of America. - 102 : 48 (2005), p. 17424-17429. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Varga József L. Toller Gábor L. Horváth Judit E. (New Orleans) Szepesházi Károly Köster, Frank Kovitz, Kevin Groot, Kate Zarándi Márta Kanashiro, Celia A.
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4.

001-es BibID:BIBFORM004056
Első szerző:Heinrich, Elmar
Cím:Dose-dependent growth inhibition in vivo of PC-3 prostate cancer with a reduction in tumoral growth factors after therapy with GHRH antagonist MZ-J-7-138 / Elmar Heinrich, Andrew V. Schally, Stefan Buchholz, Ferenc G. Rick, Halmos Gábor, Mile Melinda, Kate Groot, Florian Hohla, Zarandi Márta, Jozsef L. Varga
Dátum:2008
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various cancers and affect tumoral growth factors. Methods: We investigated the effect of a new GHRH antagonist MZ-J-7-138 at doses of 1.25, 2.5, 5 and 10 mű g/day s.c. on the growth of PC-3 human androgen independent prostate cancers xenografted s.c. into nude mice. Binding assays were used to investigate GHRH receptors. The levels of IGF-II and VEGF in tumors were measured by radioimmunoassays. Results: Treatment with 2.5, 5, and 10 mű g/day MZ-J-7-138 caused a significant dose-dependent growth reduction of PC-3 tumors. The greatest inhibition of 78% was obtained with 10 mű g/day. The suppression of IGF-II protein levels in tumors was seen at all doses of MZ-J-7-138, but only 10 microg dose induced a significant inhibition. MZ-J-7-138 also reduced VEGF protein levels, the inhibition being significant at doses of 5 and 10 microg. Specific high affinity binding sites for GHRH were found on PC-3 tumors using 125I-labeled GHRH antagonist JV-1-42. MZ-J-7-138 displaced radiolabeled JV-1-42 with an IC50 of 0.32 nM indicating its high affinity to GHRH receptors. Real-time PCR analyses detected splice variant 1 (SV1) of GHRH receptor (GHRH-R) as well as pituitary type of GHRH-R and GHRH ligand. Conclusion: Our results demonstrate the efficacy of GHRH antagonist MZ-J-7-138 in suppressing growth of PC-3 prostate cancer at doses lower than previous antagonists. The reduction of levels of growth factors such as VEGF and IGF-II in tumors by GHRH antagonist was correlated with the suppression of tumor growth.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:The Prostate. - 68 : 16 (2008), p. 1763-1772. -
További szerzők:Schally, Andrew Victor Buchholz, Stefan Rick Ferenc G. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Mile Melinda (1983-) (gyógyszerész) Groot, Kate Hohla, Florian Zarándi Márta Varga József L.
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elektronikus változat
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5.

001-es BibID:BIBFORM011626
Első szerző:Hohla, Florian
Cím:GHRH antagonist causes DNA damage leading to p21 mediated cell cycle arrest and apoptosis in human colon cancer cells / Florian Hohla, Stefan Buchholz, Andrew V. Schally, Stefan Seitz, Ferenc G. Rick, Luca Szalontay, Jozsef L. Varga, Marta Zarandi, Gabor Halmos, Irving Vidaurre, Awtar Krishan, Metin Kurtoglu, Sudhir Chandna, Elmar Aigner, Christian Datz
Dátum:2009
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Cell Cycle. - 8 : 19 (2009), p. 3149-3156. -
További szerzők:Buchholz, Stefan Schally, Andrew Victor Seitz, Stephan Rick Ferenc G. Szalontay Luca Varga József L. Zarándi Márta Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Vidaurre, Irving Krishan, Awtar Kurtoglu, Metin Chandna, Sudhir Aigner, Elmar Datz, Christian
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6.

001-es BibID:BIBFORM033567
035-os BibID:PMID:16039952 WOS:000231161800005
Első szerző:Kanashiro, Celia A.
Cím:Antagonists of growth hormone releasing hormone and bombesin inhibit the expression of EGF/HER receptor family in H-69 small cell lung carcinoma / Celia A. Kanashiro, Andrew V. Schally, Jozsef L. Varga, Brian Hammann, Gabor Halmos, Marta Zarandi
Dátum:2005
ISSN:0304-3835
Megjegyzések:Effects of in vivo treatment with antagonists of growth hormone-releasing hormone (GHRH), JV-1-65 and MZ-J-7-110, and bombesin/gastrin-releasing peptide antagonist RC-3940-II, on the EGF receptor (EGFR) family, were investigated in H-69 SCLC. Tumors were analyzed by RT-PCR, immunoblotting and binding assays. Treatment with these analogs reduced the binding capacity of EGFR by 18-64%, and inhibited the mRNA expression for EGFR, HER-2 and -3 by 27-75.4, 17-26.3, and 13.8-46.6%, respectively. The antagonists also decreased the protein levels for EGFR by 21-34%, HER-2 by 36-68% and HER-3 by 43-49%. This is the first demonstration that antiproliferative effects of GHRH antagonists are associated with a downregulation of EGF/HER receptors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer Letters. - 226 : 2 (2005), p. 123-131. -
További szerzők:Schally, Andrew Victor Varga József L. Hammann, Brian Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Zarándi Márta
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7.

001-es BibID:BIBFORM033573
035-os BibID:PMID:16027368 WOS:000230853300041
Első szerző:Keller, Gunhild
Cím:Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone / Gunhild Keller, Andrew V. Schally, Kate Groot, Gabor L. Toller, Alexandre Havt, Frank Köster, Patricia Armatis, Gabor Halmos, Marta Zarandi, Jozsef L. Varga, Jörg B. Engel
Dátum:2005
ISSN:0027-8424
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) were shown to inhibit the growth of various cancers. We investigated the antitumor activity and the mechanism of action of GHRH antagonists in human non-Hodgkin's lymphomas (NHL). Nude mice bearing xenografts of RL and HT human NHL were treated with GHRH antagonists MZ-5-156 and MZ-J-7-138 at a dose of 40 microg twice daily. The concentrations of serum IGF-1 and GHRH, bFGF, and VEGF in tumor tissue were measured by radioimmunoassays. Expression of GHRH and splice variant 1 of the GHRH receptor in both cell lines was examined by RT-PCR. The effects of MZ-5-156, MZ-J-7-138 and GHRH on cell proliferation were evaluated in vitro. Treatment with MZ-5-156 and MZ-J-7-138 significantly (P < 0.05) inhibited the growth of RL and HT tumors by 59.9-73.9%. High-affinity binding sites for GHRH and mRNA for GHRH and splice variant-1 of the GHRH receptors were found on RL and HT tumors. RL and HT cells contained GHRH peptide, and their growth in vitro was significantly inhibited by both antagonists. IGF-I levels in serum of mice were significantly decreased by antagonist MZ-5-156. Therapy with GHRH antagonists also significantly reduced tumoral bFGF, whereas VEGF levels were not suppressed. Our findings suggest that GHRH antagonists inhibit the growth of RL and HT lymphomas by direct effects mediated by tumoral receptors for GHRH. GHRH antagonists could offer a new therapeutic modality for the management of advanced NHL.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States Of America. - 102 : 30 (2005), p. 10628-10633. -
További szerzők:Schally, Andrew Victor Groot, Kate Toller Gábor L. Havt, Alexandre Köster, Frank Armatis, Patricia Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Zarándi Márta Varga József L. Engel, Jörg B.
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8.

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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9.

001-es BibID:BIBFORM033817
035-os BibID:PMID:8940358 WOS:A1996VU35100026
Első szerző:Kovács Magdolna
Cím:Effects of acute and chronic administration of a new potent antagonist of growth hormone-releasing hormone in rats : mechanisms of action / Magdolna Kovács, Márta Zarándi, Gábor Halmos, Kate Groot, Andrew V. Schally
Dátum:1996
ISSN:0013-7227
Megjegyzések:Antagonistic analogs of human GH-releasing hormone (hGHRH) are potential candidates for the treatment of disorders characterized by excessive GH secretion and especially for therapy of GH- and insulin-like growth factor (IGF)-dependent tumors. These analogs should be also useful for the studies on the mechanism of action of GHRH. In the present investigation, we evaluated the effects of chronic i.m. administration of a new potent GHRH antagonist (Ibu0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27)hGHRH(1-28)+ ++Agm (MZ-4-71) on the growth rate, serum GH, and IGF-I concentration, GH responsiveness to exogenous GHRH, as well as the pituitary GH content and GHRH receptor concentration in young female rats. We also studied the consequences of acute, high-dose i.v. application of this antagonist on the basal GH and IGF-I levels in adult male rats. In addition, the ability of GHRH antagonist MZ-4-71 to prevent GH release induced by GHRH pulses was determined in vitro in the superfused rat pituitary cell system. Chronic treatment in vivo using twice daily i.m. injections of 20 microg MZ-4-71 for 2 weeks reduced the rate of increase in body weight by 21% and in body length of young rats by 36%, as compared with controls. GH responses to bolus injections of GHRH declined by 22%, and serum IGF-I concentrations by 15% at the end of the treatment. The total pituitary GH content, but not relative GH concentration, also decreased by 15% and GHRH receptor concentration by 48%, following chronic treatment with this antagonist. Bolus injections of high doses of MZ-4-71 (400 microg i.v.) induced a marked and protracted (6 h) inhibition of the basal serum GH concentration and a parallel inhibition of the serum IGF-I levels. The nadir of both the serum GH (62% decrease) and the IGF-I level (30% decrease) was found at 3 h after the injection. In vitro studies showed that MZ-4-71 was able to dose-dependently inhibit the GH-releasing effect of GHRH pulses. Present results demonstrate that GHRH antagonist MZ-4-71 is effective in vivo and that it can inhibit growth and secretion of GH and IGF-I in rats. Our findings also provide new information on the role of GHRH in regulating synthesis of GH and GHRH receptors. It is likely that antagonistic analogs of GHRH could find clinical application for reducing the growth of tumors dependent on GH or IGF-I.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrinology. - 137 : 12 (1996), p. 5364-5369. -
További szerzők:Zarándi Márta Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Schally, Andrew Victor
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Borító:

10.

001-es BibID:BIBFORM033697
035-os BibID:WOS:A1996UW79200078
Első szerző:Nagy Attila
Cím:Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxorubicin, a derivative 500-1000 times more potent / Attila Nagy, Andrew V. Schally, Patricia Armatis, Karoly Szepeshazi, Gabor Halmos, Magdolna Kovacs, Marta Zarandi, Kate Groot, Masahiro Miyazaki, Andreas Jungwirth, Judit Horvath
Dátum:1996
ISSN:0027-8424
Megjegyzések:Doxorubicin (DOX) and its daunosamine-modified derivative, 2-pyrrolino-DOX, which is 500-1000 times more active than DOX, were incorporated into agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH), The conjugation of DOX with LH-RH analogs was performed by using N-(9-fluorenylmethoxycarbonyl)-DOX-14-O-hemiglutarate, a dicarboxylic acid ester derivative of DOX, Coupling this derivative covalently to the E-amino group of the D-Lys side chain of agonist [D-Lys(6)]LH-RH or antagonistic analog Ac-D-Nal(2)-D-Phe(4Cl)-D-Pal(3)-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-Ala-NH2 [where Nal(2) = 3-(2-naphthyl)alanine, Pal(3) = 3-(3-pyridyl)alanine, and Phe(4Cl) = 4-chlorophenylalanine] was followed by the removal of the 9-fluorenylmethoxycarbonyl protective group to yield cytotoxic derivatives of LH-RH analogs containing DOX, From these DOX containing LH-RH hybrids, intensely potent analogs with daunosamine-modified derivatives of DOX can be readily formed. Thus, cytotoxic LH-RH agonist containing DOX (AN-152) can be converted in a 66% yield by a reaction with a 30-fold excess of 4-iodobutyraldehyde in N,N-dimethylformamide into a derivative having 2-pyrrolino-DOX (AN-207). Hybrid molecules AN-152 and AN-207 fully preserve the cytotoxic activity of their radicals, DOX or 2-pyrrolino-DOX, respectively, in vitro, and also retain the high binding affinity of the peptide hormone portion of the conjugates to rat pituitary receptors for LH-RH, These highly potent cytotoxic analogs of LH-RH were designed as targeted anti-cancer agents for the treatment of various tumors that possess receptors for the carrier peptide, Initial in vivo studies show that the hybrid molecules are much less toxic than the respective cytotoxic radicals incorporated and significantly more active in inhibiting tumor growth.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 93 : 14 (1996), p. 7269-7273. -
További szerzők:Schally, Andrew Victor Armatis, Patricia Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Kovács Magdolna Zarándi Márta Groot, Kate Miyazaki, Masahiro Jungwirth, Andreas Horváth Judit E. (New Orleans)
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Borító:

11.

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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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM033839
035-os BibID:PMID:7473836 WOS:A1995TG66200013
Első szerző:Pinski, Jacek
Cím:Inhibition of growth of human osteosarcomas by antagonists of growth hormone-releasing hormone / Jacek Pinski, Andrew V. Schally, Kate Groot, Gabor Halmos, Karoly Szepeshazi, Marta Zarandi, Patricia Armatis
Dátum:1995
ISSN:0027-8874
Megjegyzések:Insulin-like growth factor I (IGF-I) may be involved in the proliferation of human osteosarcomas. Most of the IGF-I found in blood is produced in the liver, where transcription of the IGF-I gene is regulated by growth hormone (GH). Recently, we synthesized various potent antagonists of GH-releasing hormone (GH-RH), including [Ibu0, D-Arg2, Phe(4-Cl)6, Abu15, Nle27]hGH-RH(1-28)Agm, which is also called MZ-4-71. PURPOSE: We investigated the effects of this antagonist on the growth of the human osteosarcoma cell lines SK-ES-1 and MNNG/HOS, transplanted into nude mice or cultured in vitro. METHODS: Nude male mice bearing SK-ES-1 and MNNG/HOS tumors were treated for 4 and 3 weeks, respectively, with MZ-4-71 administered from osmotic minipumps at a dose of 40 micrograms per animal per day. Tumor volume, tumor weight, and levels of receptors for IGF-I were determined. IGF-I levels in serum, tumor, and liver tissue were measured by radioimmunoassay. In other experiments, tumor-bearing nude mice were treated subcutaneously for 3 weeks with the GH-RH agonist hGH-RH(1-29)NH2 or with MZ-4-71 for 13 days at doses of 50 micrograms per animal per day. Effects of MZ-4-71, hGH-RH(1-29)NH2, and human GH (hGH) on cell proliferation and on the production of IGF-I and cyclic adenosine monophosphate were also evaluated in SK-ES-1 and MNNG/HOS cells in vitro. RESULTS: The growth of SK-ES-1 and MNNG/HOS tumors in nude mice was significantly inhibited by MZ-4-71, as measured by a reduction in tumor volume and weight (all P values < .05). MZ-4-71 treatment of either SK-ES-1 or MNNG/HOS tumor-bearing animals decreased tumor tissue IGF-I levels. The growth of MNNG/HOS xenografts was stimulated by hGH-RH(1-29)NH2 (P < .01). IGF-I levels in serum of tumor-bearing nude mice treated subcutaneously for 13 days with MZ-4-71 were decreased (both P values < .01). High-affinity binding sites for IGF-I were demonstrated on cell membranes of SK-ES-1 and MNNG/HOS tumors. In cell cultures of both osteosarcomas, IGF-I production was stimulated by 25 ng/mL hGH but was not changed by 10 ng/mL hGH-RH(1-29)NH2 or 5 microM MZ-4-71. Incorporation of [3H]thymidine into DNA in SK-ES-1 (but not MNNG/HOS) cells was increased by 25 ng/mL IGF-I (P < .01). The proliferation rate of the two cell lines was not affected by 5-50 ng/mL hGH-RH(1-29)NH2 or 1-80 ng/mL hGH but was suppressed by 10(-6)-10(-5) M MZ-4-71. CONCLUSIONS: Our findings demonstrate that the GH-RH antagonist MZ-4-71 can significantly inhibit the growth of SK-ES-1 and MNNG/HOS osteosarcomas in mice.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal of The National Cancer Institute. - 87 : 23 (1995), p. 1787-1794. -
További szerzők:Schally, Andrew Victor Groot, Kate Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Zarándi Márta Armatis, Patricia
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Intézményi repozitóriumban (DEA) tárolt változat
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