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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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001-es BibID:	BIBFORM041791
Első szerző:	Rick Ferenc G.
Cím:	Shrinkage of experimental benign prostatic hyperplasia and reduction of prostatic cell volume by a gastrin-releasing peptide antagonist / Rick F. G., Abi-Chaker A., Szalontay L., Perez R., Jaszberenyi M., Jayakumar A. R., Shamaladevi N., Szepeshazi K., Vidaurre I., Halmos G., Krishan A., Block N. L., Schally A. V.
Dátum:	2013
Megjegyzések:	Gastrin releasing-peptide (GRP) is a potent growth factor in many malignancies. Benign prostatic hyperplasia (BPH) is a progressive age-related proliferation of glandular and stromal tissues; various growth factors and inflammatory processes are involved in its pathogenesis. We have demonstrated that potent antagonists of GRP inhibit growth of experimental human tumors including prostate cancer, but their effect on models of BPH has not been studied. Here, we evaluated the effects of GRP antagonist RC-3940-II on viability and cell volume of BPH-1 human prostate epithelial cells and WPMY-1 prostate stromal cells in vitro, and in testosterone-induced BPH in Wistar rats in vivo. RC-3940-II inhibited the proliferation of BPH-1 and WPMY-1 cells in a dose-dependent manner and reduced prostatic cell volume in vitro. Shrinkage of prostates was observed after 6 wk of treatment with RC-3940-II: a 15.9% decline with 25 ?g/d; and a 18.4% reduction with 50 ?g/d (P < 0.05 for all). Significant reduction in levels of proliferating cell nuclear antigen, NF-??/p50, cyclooxygenase-2, and androgen receptor was also seen. Analysis of transcript levels of genes related to growth, inflammatory processes, and signal transduction showed significant changes in the expression of more than 90 genes (P < 0.05). In conclusion, GRP antagonists reduce volume of human prostatic cells and lower prostate weight in experimental BPH through direct inhibitory effects on prostatic GRP receptors. GRP antagonists should be considered for further development as therapy for BPH.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Proceedings of the National Academy of Sciences of the United States of America. - 110 : 7 (2013), p. 2617-2622. -
További szerzők:	Abi-Chaker, Andrew Szalontay Luca Perez, Roberto Jászberényi Miklós Jayakumar, Arumugam R. Shamaladevi, Nagarajarao Szepesházi Károly Vidaurre, Irving Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Krishan, Awtar Block, Norman L. Schally, Andrew Victor
Pályázati támogatás:	TÁMOP-4.2.2.A-11/1/KONV-2012-0025 TÁMOP
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM036738
035-os BibID:	PMID:22824624
Első szerző:	Szepesházi Károly
Cím:	Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108] / Karoly Szepeshazi, Andrew V. Schally, Gunhild Keller, Norman L. Block, Daniel Benten, Gabor Halmos, Luca Szalontay, Irving Vidaurre, Miklos Jaszberenyi, Ferenc G. Rick
Dátum:	2012
Megjegyzések:	Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban Molekulatudomány külföldön készült közlemény
Megjelenés:	Oncortarget (electronic resources). - 3 : 7 (2012), p. 686-699. -
További szerzők:	Schally, Andrew Victor Keller, Gunhild Block, Norman L. Benten, Daniel Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szalontay Luca Vidaurre, Irving Jászberényi Miklós Rick Ferenc G.
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
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM072409
Első szerző:	Zarándi Márta
Cím:	Synthesis and structure-activity studies on novel analogs of human growth hormone releasing hormone (GHRH) with enhanced inhibitory activities on tumor growth / Marta Zarandi, Renzhi Cai, Magdolna Kovacs, Petra Popovics, Luca Szalontay, Tengjiao Cui, Wei Sha, Miklos Jaszberenyi, Jozsef Varga, XianYang Zhang, Norman L. Block, Ferenc G. Rick, Gabor Halmos, Andrew V. Schally
Dátum:	2017
ISSN:	0196-9781
Megjegyzések:	The syntheses and biological evaluations of new GHRH analogs of Miami (MIA) series with greatly increased anticancer activity are described. In the design and synthesis of these analogs, the following previous substitutions were conserved: D-Arg(2), Har(9), Abuls(15), and Nle(27). Most new analogs had Ala at position 8. Since replacements of both Lys(12) and Lys(21) with Orn increased resistance against enzymatic degradation, these modifications were kept. The substitutions of Arg at both positions 11 and 20 by His were also conserved. We kept D-Arg(28), Har(29) -NH2 at the C-terminus or inserted Agm or 12-amino dodecanoic acid amide at position 30. We incorporated pentafluoro-Phe (Fpa(s)), instead of Cpa, at position 6 and Tyr(Me) at position 10 and omega-amino acids at N-terminus of some analogs. These GHRH analogs were prepared by solid-phase methodology and purified by HPLC. The evaluation of the activity of the analogs on GH release was carried out in vitro on rat pituitaries and in vivo in male rats. Receptor binding affinities were measured in vitro by the competitive binding analysis. The inhibitory activity of the analogs on tumor proliferation in vitro was tested in several human cancer cell lines such as HEC-1A endometrial adenocarcinoma, HCT-15 colorectal adenocarcinoma, and LNCaP prostatic carcinoma. For in vivo tests, various cell lines including PC-3 prostate cancer, HEC-1A endometrial adenocarcinoma, HT diffuse mixed beta cell lymphoma, and ACHN renal cell carcinoma cell lines were xenografted into nude mice and treated subcutaneously with GHRH antagonists at doses of 1-5 mu g/day. Analogs MIA-602, MIA-604, MIA-610, and MIA-640 showed the highest binding affinities, 30, 58, 48, and 73 times higher respectively, than GHRH (1-29) NH2. Treatment of LNCaP and HCT-15 cells with 5 mu M MIA-602 or MIA-690 decreased proliferation by 40%-80%. In accord with previous tests in various human cancer lines, analog MIA-602 showed high inhibitory activity in vivo on growth of PC-3 prostate cancer, HT-mixed beta cell lymphoma, HEC-1A endometrial adenocarcinoma and ACHN renal cell carcinoma. Thus, GHRH analogs of the Miami series powerfully suppress tumor growth, but have only a weak endocrine GH inhibitory activity. The suppression of tumor growth could be induced in part by the downregulation of GHRH receptors levels. Published by Elsevier Inc.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Peptides. - 89 (2017), p. 60-70. -
További szerzők:	Cai, Ren-Zhi Kovács Magdolna Popovics Petra Szalontay Luca Cui, Tengjiao Sha, Wei Jászberényi Miklós Varga József XianYang, Zhang Block, Norman L. Rick Ferenc G. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Schally, Andrew Victor
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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