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1.

001-es BibID:BIBFORM033905
035-os BibID:PMID:8378189 WOS:A1993LY67100008
Első szerző:Pinski, Jacek
Cím:Inhibition of growth of experimental prostate cancer in rats by LH-RH analogs linked to cytotoxic radicals / Jacek Pinski, Andrew V. Schally, Tetsu Yano, Karoly Szepeshazi, Gabor Halmos, Kate Groot, Ana Maria Comaru-Schally, Sinisa Radulovic, Attila Nagy
Dátum:1993
ISSN:0270-4137
Megjegyzések:The effects of hybrid cytotoxic LH-RH analogs, produced by linking anthraquinone or methotrexate to carrier LH-RH agonist [D-Lys6]LH-RH, were evaluated in Copenhagen-Fisher F1 rats bearing Dunning R-3327H prostate adenocarcinoma. The two cytotoxic LH-RH analogs T-98 [(D-Lys6)LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone (G-HMAQ)], and AJ-04 [(D-Lys6)LH-RH linked to methotrexate (MTX)], carrier [D-Lys6]LH-RH, or the free cytotoxic compounds MTX and G-HMAQ were administered from Alzet Osmotic minipumps for 7-8 weeks. The cytotoxic LH-RH analogs caused somewhat greater tumor growth inhibition than the carrier peptide, while anthraquinone or methotrexate alone, administered in equimolar doses, were ineffective. The inhibition of androgen sensitive organs (testes, ventral prostates, and seminal vesicles) was pronounced with both carrier and cytotoxic analogs, showing the latter to be fully hormonally active in suppressing the pituitary-gonadal axis. Histological changes were also evaluated. The inhibition of mitosis and the frequency of apoptosis were higher in tumors treated with AJ-04, T-98, [D-Lys6]LH-RH, or by castration than in those of controls. Serum hormone levels were lowered by both carrier peptide and cytotoxic analogs, LH being substantially depressed, and testosterone not detectable. These results and other findings indicate that LH-RH analogs containing cytotoxic radicals anthraquinone or methotrexate retain their hormonal activity after administration in vivo, and can effectively inhibit tumor growth. Extensive further studies are required on this new class of compounds, but apparent binding of cytotoxic LH-RH analogs to tumors such as prostate cancer, which have receptors for LH-RH, could greatly reduce peripheral toxicity of chemotherapeutic agents. This approach, based on targeted chemotherapy, might be of practical therapeutic importance for the management of advanced prostate cancers, which eventually relapse after palliative hormonal therapy.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Prostate. - 23 : 2 (1993), p. 165-178. -
További szerzők:Schally, Andrew Victor Yano, Tetsu Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Comaru-Schally, Ana Maria Radulovic, Sinisa Nagy Attila
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2.

001-es BibID:BIBFORM033896
035-os BibID:PMID:7910153 WOS:A1994NL69800021
Első szerző:Pinski, Jacek
Cím:Inhibition of growth of MKN45 human gastric-carcinoma xenografts in nude mice by treatment with bombesin/gastrin-releasing-peptide antagonist (RC-3095) and somatostatin analogue RC-160 / Jacek Pinski, Gabor Halmos, Tetsu Yano, Karoly Szepeshazi, Yunfeng Qin, Tibor Ertl, Andrew V. Schally
Dátum:1994
ISSN:0020-7136
Megjegyzések:Nude mice bearing xenografts of the gastrin-responsive human gastric carcinoma MKN45 cell line were treated for 4 to 5 weeks with bombesin/gastrin-releasing-peptide(GRP) antagonist (RC-3095), somatostatin analogues RC-160 and SMS 201-995, or the combination of RC-3095 and RC-160. Tumor volumes and weights were reduced significantly to a similar extent by RC-160 and SMS 201-995, administered by daily s.c. injections at a dose of 100 micrograms/day. Bombesin/GRP antagonist RC-3095, given s.c. at a dose of 20 micrograms/day, had the greatest inhibitory effect on tumor growth. The combination of RC-3095 with RC-160 did not further potentiate the suppression of tumor growth. Histologically, the number of mitotic cels decreased significantly in the groups treated with RC-160 or the combination of RC-3095 with RC-160. Serum gastrin levels were significantly diminished in all treated groups. Therapy with RC-160 or the combination also significantly decreased levels of serum growth hormone. Receptor assays on tumor membranes showed that bombesin was bound to 2 classes of receptor sites, one with high affinity and low capacity, the other with low affinity and high capacity. Binding sites for epidermal growth factor (EGF) were down-regulated in tumor cells after treatment with RC-3095, RC-160 or the combination of RC-3095 with RC-160. In studies in vitro, both RC-160 and RC-3095 significantly inhibited the proliferation of MKN45 cells in culture as measured by cell number. These data demonstrate, for the first time, that the growth of human gastric cancer in nude mice can be inhibited not only by somatostatin analogues, but also by administration of modern bombesin/GRP antagonists, such as RC-3095.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:International Journal of Cancer. - 57 : 4 (1994), p. 574-580. -
További szerzők:Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Yano, Tetsu Szepesházi Károly Qin, Yunfeng Ertl Tibor Schally, Andrew Victor
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3.

001-es BibID:BIBFORM033892
035-os BibID:PMID:7946450 WOS:A1994PT77400018
Első szerző:Radulovic, Sinisa
Cím:Inhibitory effects of antagonists of bombesin/gastrin releasing peptide (GRP) and somatostatin analog (RC-160) on growth of HT-29 human colon cancers in nude mice / Sinisa Radulovic, Andrew V. Schally, Herta Reile, Gabor Halmos, Karoly Szepeshazi, Kate Groot, Slobodan Milovanovic, Glenn Miller, Tetsu Yano
Dátum:1994
Megjegyzések:Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with somatostatin analog (RC-160), bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095 and RC-3440). In three separate experiments somatostatin analog RC-160 (50 micrograms/day) released from microgranules significantly reduced tumor growth. Bombesin/GRP antagonists, RC-3095 and RC-3440 injected subcutaneously (s.c.) twice daily at a dose of 10 micrograms had the greatest and consistently significant inhibitory effect on tumor growth. RC-3095 given once daily s.c. at a dose of 20 micrograms was less effective. RC-3095 also inhibited metastatic tumor growth after intrasplenic injection of HT-29 cells in nude mice. Specific binding sites of somatostatin, bombesin and epidermal growth factor (EGF) were detected on intact HT-29 cells or on the membranes from HT-29 tumor xenografts. The inhibitory effects of bombesin antagonists on tumor growth were consistently linked with a significant down-regulation of EGF receptors. Bombesin/GRP antagonists and somatostatin analogs could be considered for the development of new hormonal therapies for colon cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Acta oncologica. - 33 : 6 (1994), p. 693-701. -
További szerzők:Schally, Andrew Victor Reile, Herta Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Groot, Kate Milovanovic, Slobodan Miller, Glenn Yano, Tetsu
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4.

001-es BibID:BIBFORM033849
035-os BibID:WOS:A1994NE25400712
Első szerző:Schally, Andrew Victor
Cím:Antitumor effects of analogs of LH-RH, somatostatin and bombesin/GRP in experimental models of breast and prostate cancer / Andrew V. Schally, Jacek Pinski, Karoly Szepeshazi, Tetsu Yano, Gabor Halmos, Yutaka Shirahige, Ana Maria Comaru-Schally, Ren-Zhi Cai, Attila Nagy
Dátum:1994
ISSN:0730-2312
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idézhető absztrakt
Megjelenés:Journal of Cellular Biochemistry. - 18D (1994), p. 222. -
További szerzők:Pinski, Jacek Szepesházi Károly Yano, Tetsu Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Shirahige, Yutaka Comaru-Schally, Ana Maria Cai, Ren-Zhi Nagy Attila
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5.

001-es BibID:BIBFORM033841
Első szerző:Schally, Andrew Victor
Cím:LHRH analogs with cytotoxic radicals / A. V. Schally, A. Nagy, K. Szepeshazi, J. Pinski, G. Halmos, P. Armatis, M. Miyazaki, A. M. Comaru-Schally, T. Yano, G. Emons
Dátum:1995
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok előadáskivonat
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Megjelenés:Treatment with GnRH Analogues / [eds. Roger D. Kempers ... et al]. - p. 33-44.
További szerzők:Nagy Attila Szepesházi Károly Pinski, Jacek Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Armatis, Patricia Miyazaki, Masahiro Comaru-Schally, Ana Maria Yano, Tetsu Emons, G.
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6.

001-es BibID:BIBFORM033742
035-os BibID:PMID:8313327 WOS:A1994MY53800016
Első szerző:Yano, Tetsu
Cím:Inhibitory effect of bombesin/gastrin-releasing peptide antagonist RC-3095 and luteinizing hormone-releasing hormone antagonist SB-75 on the growth of MCF-7 MIII human breast cancer xenografts in athymic nude mice / Tetsu Yano, Jacek Pinski, Karoly Szepeshazi, Gabor Halmos, Sinisa Radulovic, Kate Groot, Andrew V. Schally
Dátum:1994
ISSN:0008-543X
Megjegyzések:The results of several clinical trials using various luteinizing hormone-releasing hormone agonists for treatment of advanced breast cancer are encouraging. However, only about 30% of breast cancers are estrogen-dependent and can be treated by hormonal manipulation. New therapeutic approaches combining estrogen ablation therapy with other compounds must be explored. Various studies suggest that bombesin or gastrin-releasing peptide acts as an autocrine growth factor and may play a role in the initiation and progression of some cancers, including that of the breast. METHODS: Female athymic nude mice bearing xenografts of the MCF-7 MIII human breast cancer cell line were treated for 7 weeks with bombesin/gastrin-releasing peptide antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin(6-14) (RC-3095) injected subcutaneously daily at a dose of 20 micrograms and luteinizing hormone-releasing hormone antagonist SB-75 (Cetrorelix) administered biweekly in the form of microgranules releasing 45 micrograms/day. RESULTS: After 2 weeks of treatment, a significant inhibition of tumor volume was observed in the groups treated with RC-3095 alone or in combination with SB-75 but not in those treated with SB-75 as a single agent. After 7 weeks, tumor growth as measured by tumor volume and percentage changes in tumor volume and tumor weight was greatly inhibited in all of the treated groups. Uterine and ovarian weights were reduced and serum luteinizing hormone levels decreased by administration of SB-75 alone or in combination with RC-3095. Histologically, a significant decrease in argyrophilic nucleolar organizer region count in tumor cell nuclei was observed in all of the treated groups, indicating a lower proliferation of these cells. High-affinity binding sites for bombesin were detected in cultured MCF-7 MIII cells. Chronic treatment with RC-3095 caused a significant down-regulation of epidermal growth factor receptors in tumor cell membranes, which might be related to tumor inhibition. In studies in vitro, SB-75 inhibited proliferation of MCF-7 cells in culture but not proliferation of MCF-7 MIII cells. CONCLUSIONS: Because previously we demonstrated that RC-3095 inhibits the proliferation of MCF-7 MIII cells in vitro, it appears that the major antitumoral effect of RC-3095 on the MCF-7 MIII cancer line is direct, whereas that of SB-75 is indirect, and that it is mediated by suppression of the pituitary-gonadal axis. In view of its immediate and powerful inhibitory effect on MCF-7 MIII tumors, bombesin/gastrin-releasing peptide antagonist RC-3095 might be considered as a possible new agent for the treatment of breast cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Cancer. - 73 : 4 (1994), p. 1229-1238. -
További szerzők:Pinski, Jacek Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Radulovic, Sinisa Groot, Kate Schally, Andrew Victor
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7.

001-es BibID:BIBFORM033741
035-os BibID:WOS:A1994NY34800071
Első szerző:Yano, Tetsu
Cím:Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75 / Tetsu Yano, Jacek Pinski, Gabor Halmos, Karoly Szepeshazi, Kate Groot, Andrew V. Schally
Dátum:1994
ISSN:0027-8424
Megjegyzések:Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer cell line were treated with potent luteinizing hormone (LH)-releasing hormone (LH-RH) antagonist SB-75 (Cetrorelix; [Ac-D-Nal(2)(1), D-Phe(4 Cl)(2), D-Pal(3)(3), D-Cit(6), D-Ala(10)]LH-RH in which Ac-D-Nal(2) = N-acetyl-3-(2-naphthyl)-D-alanine, D-Phe(4Cl) = 4-chloro-D-phenylalanine, D-Pal(3) = 3-(3-pyridyl)-D-alanine, and D-Cit = D-Citrulline) of with the agonist [D-Trp(6)]LH-RH. In the first experiment, SB-75 and [D-Trp(6)]LH-RH were administered in the form of microcapsules releasing 60 and 25 mu g/day, respectively. In the second study, the analogs were given by daily s.c. injections in doses of 100 mu g/day. In both experiments, tumor growth, as measured by reduction in tumor volume, percentage change in tumor volume, tumor burden, and increase in tumor doubling time, was significantly inhibited by treatment with SB-75 but not with [D-Trp(6)]LH-RH. Uterine and ovarian weights were reduced and serum LH levels decreased by administration of either analog. Chronic treatment with SB-75 greatly reduced the concentration of receptors for epidermal growth factor and insulin-like growth factor I in tumor cell membranes, a phenomenon that might be related to tumor growth inhibition. It is possible that the antitumoral effects of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression of the pituitary-gonadal axis, but also directly. In view of its strong inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH-RH antagonist SB-75 might be considered for possible hormonal therapy of advanced epithelial ovarian carcinoma.
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. - 91 : 15 (1994), p. 7090-7094. -
További szerzők:Pinski, Jacek Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Groot, Kate Schally, Andrew Victor
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