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001-es BibID:BIBFORM033758
035-os BibID:WOS:A1997YH75900014
Első szerző:Miyazaki, Masahiro
Cím:Growth inhibition of human ovarian cancers by cytotoxic analogues of luteinizing hormone-releasing hormone / Masahiro Miyazaki, Attila Nagy, Andrew V. Schally, Najib Lamharzi, Gabor Halmos, Karoly Szepeshazi, Kate Groot, Patricia Armatis
Dátum:1997
ISSN:0027-8874
Megjegyzések:Background: Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in nearly 80% of human ovarian cancers. The chemotherapeutic agent doxorubicin can be linked to [D-lysine(6)]LH-RH to form a cytotoxic analogue (AN-152) that may have greater specificity for tumor cells. This study was conducted to investigate the effects of AN-152 on the growth of LH-RH receptor-positive OV-1063 human epithelial ovarian cancers. Methods: Nude mice bearing human ovarian tumors, OV-163 or UCI-107 (LH-RH recpetor negative), were injected intraperitoneally with saline (control) or with equimolar doses of AN-152 or doxorubicin; experiments involving mice with OV-1063 tumors also included groups that were administered [D-lysine(6)]LH-RH either alone or in combination with doxorubicin. Tumor volume, weight, doubling time, and burden (i.e, tumor weight/body weight) as well as tumor apoptotic and mitotic indices were determined. The levels of receptors for LH-RH and epidermal growth factor (EGF) and their messenger RNAs were measured by use of radioreceptor and reverse transcription-polymerase chain reaction assays respectively. Results: The growth of OV-1063 ovarian tumors in nude mice as based on reduction in tumor volume, was inhibited significantly (all P,.05, two-sided) 4 weeks after treatment with AN-152, even at the lowest dose tested (413 nmol/20g weight); the toxic effects of an equivalent dose of doxorubicin caused substantial mortality. High-affinity receptors for LH-RH and EGF were found on cell membranes of OV-1063 cancers; however, after in vivo treatment with AN-152, LH-RH receptor-binding sites were not detectable and EGF receptors were reduced in number. The growth of UCI-107 ovarian cancers was not inhibited by AN-152. Conclusions: In nude mice bearing LH-RH receptor positive OV-1063 epithelial ovarian cancers, systemic administration of AN-152 is less toxic and inhibits tumor growth better than equimolar doses of doxorubicin.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Journal of The National Cancer Institute. - 89 : 23 (1997), p. 1803-1809. -
További szerzők:Nagy Attila Schally, Andrew Victor Lamharzi, Najib Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Groot, Kate Armatis, Patricia
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2.

001-es BibID:BIBFORM033673
035-os BibID:PMID:9713279 WOS:000073781500024
Első szerző:Miyazaki, Masahiro
Cím:Inhibition of growth of MDA-MB-231 human breast cancer xenografts in nude mice by bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095 / M. Miyazaki, N. Lamharzi, A. V. Schally, G. Halmos, K. Szepeshazi, K. Groot, R. Z. Cai
Dátum:1998
ISSN:0959-8049
Megjegyzések:Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growth factors and play a role in the initiation and progression of breast cancer. We investigated the effect of bombesin/GRP antagonists RC-3095 and RC-3940-II on the growth of the MDA-MB-231 oestrogen-independent human breast cancer cell line xenografted into female nude mice. Bombesin/GRP antagonists, RC-3095 and RC-3940-II, were administered subcutaneously twice daily at a dose of 10 micrograms for 5 weeks. The growth of MDA-MB-231 tumours was inhibited during the treatment, as shown by a reduction in tumour volume. RC-3940-II and RC-3095 significantly decreased the final tumour volume by 72.4% and 57.7%, respectively, and greatly reduced tumour weights. RC-3940-II also significantly increased tumour doubling time and appeared to be more effective than RC-3095 in inhibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and insulin-like growth factor-I (IGF-I) levels in animals treated with RC-3095 or RC-3940-II showed no significant changes as compared with controls. There was a significant decrease in the number of binding sites for epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be related to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a reduction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists such as RC-3095 or RC-3940-II could be considered for endocrine therapy for oestrogen-independent breast cancers, but further investigations are necessary.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:European Journal of Cancer. - 34 : 5 (1998), p. 710-717. -
További szerzők:Lamharzi, Najib Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Groot, Kate Cai, Ren-Zhi
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3.

001-es BibID:BIBFORM033661
035-os BibID:PMID:10329861 WOS:000080603000008
Első szerző:Miyazaki, Masahiro
Cím:Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits growth of OV-1063 human epithelial ovarian cancers in nude mice / Masahiro Miyazaki, Andrew V. Schally, Attila Nagy, Najib Lamharzi, Gabor Halmos, Karoly Szepeshazi, Patricia Armatis
Dátum:1999
ISSN:0002-9378
Megjegyzések:OBJECTIVE: The aim of the study was to investigate the effects of the cytotoxic analog of luteinizing hormone-releasing hormone AN-207 on the growth of the OV-1063 human epithelial ovarian cancers, which express luteinizing hormone-releasing hormone receptor. AN-207 consists of doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) linked with the carrier [D-lysine6 ]luteinizing hormone-releasing hormone. STUDY DESIGN: Female nude mice bearing xenografts of OV-1063 ovarian cancers were treated with analog AN-207, cytotoxic radical AN-201, or agonist [D-lysine6 ]luteinizing hormone-releasing hormone. The levels and expression of messenger ribonucleic acid of receptors for luteinizing hormone-releasing hormone and epidermal growth factor were evaluated. RESULTS: The growth of OV-1063 tumor was significantly inhibited by 3 to 5 nmol AN- 207 but not by [D-lysine6 ]luteinizing hormone-releasing hormone. Cytotoxic radical AN-201 was toxic at these doses. After treatment with AN-207 receptors for luteinizing hormone-releasing hormone were not detectable, epidermal growth factor receptor levels declined, and expressions of their respective messenger ribonucleic acids were decreased. CONCLUSIONS: Targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207 is less toxic than equimolar doses of its radical 2-pyrrolinodoxorubicin and effectively inhibits ovarian tumor growth. Targeted chemotherapy may improve management of ovarian cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:American Journal of Obstetrics and Gynecology. - 180 : 5 (1999), p. 1095-1103. -
További szerzők:Schally, Andrew Victor Nagy Attila Lamharzi, Najib Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Armatis, Patricia
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4.

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
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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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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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