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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: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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3.

001-es BibID:BIBFORM033887
035-os BibID:WOS:A1994PN72200048
Első szerző:Schally, Andrew Victor
Cím:Combined hormonal therapy and chemotherapy for pancreatic cancer; use of cytotoxic peptide analogs for targeted chemotherapy / A. V. Schally, A. Nagy, R.-Z. Cai, H. Reile, S. Radulovic, Y. Qin, K. Szepeshazi, G. Halmos, Ana Maria Comaru-Schally
Dátum:1994
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:International Journal of Pancreatology. - 16 : 2-3 (1994), p. 277-280. -
További szerzők:Nagy Attila Cai, Ren-Zhi Reile, Herta Radulovic, Sinisa Qin, Yunfeng Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Comaru-Schally, Ana Maria
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4.

001-es BibID:BIBFORM033907
035-os BibID:PMID:1460673 WOS:A1992KB98400016
Első szerző:Szepesházi Károly
Cím:Growth inhibition of estrogen-dependent and estrogen-independent MXT mammary cancers in mice by the bombesin and gastrin-releasing peptide antagonist RC-3095 / Karoly Szepeshazi, Andrew V. Schally, Gabor Halmos, Kate Groot, Sinisa Radulovic
Dátum:1992
ISSN:0027-8874
Megjegyzések:Many breast cancers are estrogen independent, and even in patients who initially respond to estrogen suppression therapy, the regression is often temporary. We have recently shown that antagonists of bombesin and gastrin-releasing peptide, including RC-3095, inhibit the growth of pancreatic, colonic, and prostatic cancers in experimental animals. This effect was associated with a substantial decrease in epidermal growth factor (EGF) receptor levels in pancreatic and colon cancers. PURPOSE: In view of these findings, we investigated the effects of our synthetic bombesin and gastrin-releasing peptide receptor antagonist D-Tpi6,Leu13 psi (CH2NH)-Leu14 bombesin(6-14) (RC-3095) on the growth of hormone-dependent and hormone-independent MXT mouse mammary cancers in vivo. METHODS: Female (C57BL x DBA/2)F1 mice bearing estrogen-dependent or estrogen-independent MXT mammary carcinomas were treated with small doses (20 micrograms/d) of RC-3095 administered from osmotic minipumps. Separate groups of mice with estrogen-independent tumors received RC-3095, bombesin, or gastrin-releasing peptide(14-27) at 20 micrograms/d. We determined tumor volume and weight, mitotic index, apoptosis (programmed cell death), and argyrophilic nucleolar organizer regions, an indicator of tumor cell proliferation. Levels of receptors for EGF and bombesin were measured in tumor membrane fractions. RESULTS: Growth of both estrogen-dependent and estrogen-independent MXT breast cancers was significantly inhibited by RC-3095. Bombesin or gastrin-releasing peptide had no effect on the growth of estrogen-independent tumors. Inhibition of tumor cell proliferation was indicated by a 45%-65% reduction in tumor volume, a 35%-58% reduction in tumor weight, and statistically significant decreases in argyrophilic nucleolar organizer region counts after treatment with RC-3095. In estrogen-independent cancers, tumor inhibition was associated with a decrease in the capacity of EGF receptors from 0.21 +/- 0.016 pmol/mg membrane protein in controls to 0.03 +/- 0.003 pmol/mg membrane protein in the RC-3095-treated group. CONCLUSIONS: This is the first demonstration of inhibitory effects of bombesin and gastrin-releasing peptide antagonists on the growth of breast cancers in vivo. IMPLICATIONS: These findings suggest that bombesin antagonists should be considered for breast cancer therapy.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Journal of The National Cancer Institute. - 84 : 24 (1992), p. 1915-1922. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Radulovic, Sinisa
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5.

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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