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1.

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
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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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2.

001-es BibID:BIBFORM033538
035-os BibID:WOS:000240968100047
Első szerző:Hohla, Florian
Cím:Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel / Florian Hohla, Andrew V. Schally, Karoly Szepeshazi, Jozsef L. Varga, Stefan Buchholz, Frank Köster, Elmar Heinrich, Gabor Halmos, Ferenc G. Rick, Chandrika Kannadka, Christian Datz, Celia A. Kanashiro
Dátum:2006
ISSN:0027-8424
Megjegyzések:We investigated the effect of antagonists of growth hormone-releasing hormone (GHRH) MZ-J-7-138 and JV-1-92 on H460 human non-small cell lung carcinoma (NSCLC) xenografted orthotopically into nude mice. Treatment with MZ-J-7-138 or JV-1-92 inhibited orthotopic growth of H460 NSCLC by 52-65% (P < 0.001) and was associated with a significant decrease in protein expression of K-Ras, cyclooxygenase-2 (Cox-2) and phospho-Akt (pAkt). in other experiments, treatment with MZ-J-7-138 or docetaxel reduced tumor volume of s.c. xenografted H460 human NSCLC by 30-36% (P < 0.01). The combination of MZ-J-7-138 and docetaxel resulted in a synergistic growth inhibition of H460 NSCLC xenografts of 63%. MZ-J-7-138 alone or in combination with docetaxel significantly reduced protein levels of K-Ras, Cox-2, and pAkt by 56-63%. Docetaxel given singly diminished the protein levels only of Cox-2 and did not affect K-Ras and pAkt. High-affinity binding sites, mRNA, and protein expression of pituitary GHRH receptors and its splice variant (SV) 1 were found in H460. H460 NSCLC cells contained GHRH peptide, and its growth was significantly inhibited in vitro by 10 mu M MZ-J-7-138 (P < 0.001). Serum insulin-like growth factor 1 (IGF1) was not reduced by either GHRH antagonists. These findings suggest that antiproliferative effects of GHRH antagonists in H460 NSCLC are associated with down-regulation of K-Ras, Cox-2, and pAkt. In conclusion, GHRH antagonists in combination with docetaxel synergistically inhibit growth of H460 NSCLC and the expression of K-ras, Cox-2, and pAkt, which might abrogate the signal transduction pathways for cell growth stimulation and therapeutic resistance.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 103 : 39 (2006), p. 14513-14518. -
További szerzők:Schally, Andrew Victor Szepesházi Károly Varga József L. Buchholz, Stefan Köster, Frank Heinrich, Elmar Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Rick Ferenc G. Kannadka, Chandrika Datz, Christian Kanashiro, Celia A.
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3.

001-es BibID:BIBFORM002243
Első szerző:Hohla, Florian
Cím:Growth inhibition of non-small-cell lung carcinoma by BN/GRP antagonist is linked with suppression of K-Ras, COX-2, and pAkt / Hohla F., Schally A. V., Kanashiro C. A., Buchholz S., Baker B., Kannadka C., Moder A., Aigner E., Datz C., Halmos G.
Dátum:2007
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Proceedings of National Academy of Sciences of the United States of America. - 104 : 47 (2007), p. 18671-18676. -
További szerzők:Schally, Andrew Victor Kanashiro, Celia A. Buchholz, Stefan Baker, Benjamin Kannadka, Chandrika Moder, Angelika Aigner, Elmar Datz, Christian Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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4.

001-es BibID:BIBFORM033713
Első szerző:Kanashiro, Celia A.
Cím:Inhibition of experimental U-118MG glioblastoma by targeted cytotoxic analogs of bombesin and somatostatin is associated with a suppression of angiogenic and antiapoptotic mechanisms / Celia A. Kanashiro, Andrew V. Schally, Attila Nagy, Gabor Halmos
Dátum:2005
Megjegyzések:Human gliomas express receptors for bombesin and somatostatin that can be used for targeted chemotherapy. In the present study, the efficacy and the mechanism of action of cytotoxic bombesin analog AN-215, and cytotoxic somatostatin analog AN-238 were investigated in U-118MG human glioblastomas xenografted into nude mice. The expression of vascular endothelial growth factor (VEGF) and the apoptotic markers Bcl-2 and Bax was analyzed by Western blotting. The toxicity was evaluated by measuring leukocyte levels and body weights. Treatment with AN-215 or AN-238 reduced tumor growth by approximately 50%, and diminished the levels of VEGF by 45 and 75%, respectively. The relative ratio of Bcl-2 to Bax proteins was decreased by approximately 90%, indicating a net apoptotic gain and efficacy of treatment. Specific receptors for bombesin and somatostatin were found in U-118MG tumors. Our results suggest that targeted cytotoxic analogs, AN-215 and AN-238, could be useful for the treatment of human glioblastomas.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:International Journal of Oncology. - 27 : 1 (2005), p. 169-174. -
További szerzők:Schally, Andrew Victor Nagy Attila Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM033583
035-os BibID:PMID:15655413 WOS:000227099800007
Első szerző:Kanashiro, Celia A.
Cím:Antagonists of bombesin/gastrin-releasing peptide decrease the expression of angiogenic and anti-apoptotic factors in human glioblastoma / Celia A. Kanashiro, Andrew V. Schally, R.-Z. Cai, Gabor Halmos
Dátum:2005
ISSN:0959-4973
Megjegyzések:We have investigated the antitumor effects and the mechanism of action of antagonists of bombesin/gastrin-releasing peptide (GRP), RC-3940-II and RC-3940-Et, on the growth of U-118MG human malignant glioma xenografted into nude mice. Tumors volume was measured weekly, and after 6 weeks of treatment with GRP antagonists the tumors were analyzed by Western blot assays for the expression of vascular endothelial growth factor (VEGF), protein kinase C (PKC)-alpha, the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax. A radioreceptor assay was used to characterize the receptors for bombesin/GRP. Specific high-affinity receptors for bombesin were found in U-118MG tumors, and their growth was reduced by 52.5% by RC-3940-II and 72.6% by RC-3940-Et (both p<0.01). The tumor doubling time was prolonged by 4.6 and 12 days after treatment with RC-3940-II and RC-3940-Et, respectively, compared to controls (p<0.05). Both antagonists caused a significant (p<0.05) decrease of about 28% in the levels of VEGF protein and a reduction of approximately 35% in the expression of PKCalpha. The relative ratio of Bcl-2:Bax was also diminished by around 70% by both analogs, indicating a net apoptotic gain and the efficacy of treatment. Our results suggest that bombesin/GRP antagonists, RC-3940-II and RC-3940-Et, could be of value for the treatment of human glioblastomas.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Anti-Cancer Drugs. - 16 : 2 (2005), p. 159-165. -
További szerzők:Schally, Andrew Victor Cai, Ren-Zhi Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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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
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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:BIBFORM033546
035-os BibID:WOS:000234838300009 PMID:16173040
Első szerző:Stangelberger, Anton
Cím:Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207 / Anton Stangelberger, Andrew V. Schally, Attila Nagy, Karoly Szepeshazi, Celia A. Kanashiro, Gabor Halmos
Dátum:2006
ISSN:0270-4137
Megjegyzések:BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys(6)] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75% (P < 0.01) and LuCaP-35 human prostate cancers by 80% (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Prostate. - 66 : 2 (2006), p. 200-210. -
További szerzők:Schally, Andrew Victor Nagy Attila Szepesházi Károly Kanashiro, Celia A. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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8.

001-es BibID:BIBFORM002244
Első szerző:Stangelberger, Anton
Cím:The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers / Stangelberger A., Schally A. V., Zarandi M., Heinrich E., Groot K., Havt A., Kanashiro C. A., Varga J. L., Halmos G.
Dátum:2007
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:The Prostate. - 67 : 12 (2007), p. 1339-1353. -
További szerzők:Schally, Andrew Victor Zarándi Márta Heinrich, Elmar Groot, Kate Havt, Alexandre Kanashiro, Celia A. Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:elektronikus változat
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9.

001-es BibID:BIBFORM033595
035-os BibID:PMID:14633721 WOS:000186770700057
Első szerző:Szereday Zoltán
Cím:Antagonists of growth hormone-releasing hormone inhibit the proliferation of experimental non-small cell lung carcinoma / Zoltan Szereday, Andrew V. Schally, Jozsef L. Varga, Celia A. Kanashiro, Francine Hebert, Patricia Armatis, Kate Groot, Karoly Szepeshazi, Gabor Halmos, Rebeca Busto
Dátum:2003
ISSN:0008-5472
Megjegyzések:Recent studies show that antagonists of growth hormone-releasing hormone (GH-RH) inhibit proliferation of various cancers indirectly through blockage of the endocrine GH-insulin-like growth factor (IGF) I axis and directly by an action on tumor cells involving the suppression of autocrine/paracrine IGF-I, IGF-II, or GH-RH. The effectiveness of therapy with GH-RH antagonist JV-1-38 and its mechanisms of action were investigated in NCI-H838 non-small cell lung carcinoma (NSCLC) xenografted s.c. into nude mice and in vitro. Treatment with GH-RH antagonist JV-1-38 significantly (P < 0.05-0.001) inhibited tumor growth as demonstrated by a 58% decrease in final tumor volume, 54% reduction in tumor weight, and the extension of tumor-doubling time from 8.5 +/- 1.38 to 12 +/- 1.07 days as compared with controls. Using ligand competition assays with (125)I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-PCR revealed the expression of mRNA for GH-RH and splice variant 1 (SV(1)) of GH-RH receptor in H838 tumors. Reverse transcription-PCR analysis also demonstrated that H838 tumors express IGF-I and IGF-I receptors. Tumoral concentration of IGF-I and its mRNA expression were significantly decreased by 25% (P = 0.05) and 65% (P < 0.001), respectively, in animals receiving JV-1-38, whereas serum IGF-I levels remained unchanged. In vitro studies showed that H838 cells secreted GH-RH and IGF-I into the medium. The growth of tumor cells in vitro was stimulated by IGF-I and inhibited by GH-RH antagonist JV-1-38 and a GH-RH antiserum. Our results extend the findings on the involvement of IGF-I in NSCLC and suggest that GH-RH may be an autocrine growth factor for H838 NSCLC. The antitumorigenic action of GH-RH antagonists could be partly direct and mediated by SV(1) of tumoral GH-RH receptors. The finding of GH-RH and SV(1) of GH-RH receptors in NSCLC provides a new approach to the treatment of this malignancy based on the use of antagonistic analogues of GH-RH.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer Research. - 63 : 22 (2003), p. 7913-7919. -
További szerzők:Schally, Andrew Victor Varga József L. Kanashiro, Celia A. Hebert, Francine Armatis, Patricia Groot, Kate Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Busto, Rebeca
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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