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001-es BibID:	BIBFORM033575
035-os BibID:	PMID:15994963 WOS:000230165000049
Első szerző:	Keller, Gunhild
Cím:	Human malignant melanomas express receptors for luteinizing hormone releasing hormone allowing targeted therapy with cytotoxic luteinizing hormone releasing hormone analogue / Gunhild Keller, Andrew V. Schally, Timo Gaiser, Attila Nagy, Benjamin Baker, Gabriela Westphal, Gabor Halmos, Jörg B. Engel
Dátum:	2005
ISSN:	0008-5472
Megjegyzések:	Cytotoxic analogue of luteinizing hormone releasing hormone (LHRH), AN-207, binds with high affinity to LHRH receptors and can be targeted to tumors expressing these receptors. We investigated the expression of LHRH receptors in surgical specimens of human malignant melanoma and evaluated the effects of AN-207 in models of human melanoma. Human melanoma specimens derived from primary tumors or metastases were examined for LHRH receptor expression by immunohistochemistry. Binding assays, Western immunoblotting, and reverse transcription-PCR analyses were used to investigate LHRH receptors in MRI-H255 and MRI-H187 transplantable human melanoma tumor lines. Antitumor effects of AN-207 and its components were evaluated in vivo in nude mice bearing xenografts of either melanoma tumor line. All 19 human melanoma specimens examined showed positive staining for LHRH receptors. The mRNA for LHRH receptors, receptor protein and binding sites for LHRH were detected in both transplantable melanoma tumor lines. AN-207 significantly inhibited the growth of MRI-H255 and MRI-H187 xenografts in vivo, reducing tumor volume by 59.9% to 79.2% and tumor weight by 61.0% to 76.9% (all P < 0.05). The components of AN-207 (LH-RH analogue carrier and cytotoxic radical AN-201 as single drugs or as an unconjugated mixture) had no significant effects. Blockade of LHRH receptors by an excess of LHRH agonist Decapeptyl suppressed the effects of AN-207. LHRH receptors are expressed in a very high percentage of human malignant melanoma specimens and can be used for targeted chemotherapy with cytotoxic LHRH analogue AN-207.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Cancer Research. - 65 : 13 (2005), p. 5857-5863. -
További szerzők:	Schally, Andrew Victor Gaiser, Timo Nagy Attila Baker, Benjamin Westphal, Gabriela Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Engel, Jörg B.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM033572
035-os BibID:	PMID:16061872 WOS:000230878900030
Első szerző:	Keller, Gunhild
Cím:	Receptors for luteinizing hormone releasing hormone expressed on human renal cell carcinomas can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone analogues / Gunhild Keller, Andrew V. Schally, Timo Gaiser, Attila Nagy, Benjamin Baker, Gabor Halmos, Jörg B. Engel
Dátum:	2005
ISSN:	1078-0432
Megjegyzések:	PURPOSE: To determine the expression of luteinizing hormone releasing hormone (LHRH) receptors in specimens and cell lines of human renal cell carcinoma (RCC) and to evaluate the antitumor efficacy of targeted therapy with a cytotoxic analogue of LHRH, AN-207, in vivo. AN-207, consisting of [D-Lys(6)] LHRH linked to a cytotoxic radical, 2-pyrrolinodoxorubicin (AN-201), binds with high affinity to LHRH receptors and can be targeted to tumors expressing these receptors. EXPERIMENTAL DESIGN: The expression of LHRH receptors was investigated in 28 surgically removed specimens of human renal cell carcinoma (RCC) by immunohistochemistry and in three human RCC cell lines A-498, ACHN, and 786-0 by radioreceptor assays, Western immunoblotting, and reverse transcription-PCR analysis. Antitumor efficacy of AN-207 was examined in experimental models of these cell lines. RESULTS: Positive staining for LHRH receptors was found in all (28 of 28) of the examined human RCC specimens. mRNA for LHRH receptor, receptor protein, and LHRH binding sites were detected in all three cell lines. AN-207 significantly (P < 0.05) inhibited the growth of A-498, ACHN, and 786-0 xenografts in vivo producing a 67.8% to 73.8% decrease in tumor volume and a 62.2% to 77.3% reduction in tumor weight. Nontargeted cytotoxic radical AN-201 had no significant antitumor effects. Blockade of LHRH receptors by an excess of LHRH agonist Decapeptyl suppressed tumor inhibitory effects of AN-207. CONCLUSIONS: Our findings indicate that LHRH receptors are expressed in human RCC specimens and can be used for targeted chemotherapy with cytotoxic LHRH analogues.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Clinical Cancer Research. - 11 : 15 (2005), p. 5549-5557. -
További szerzők:	Schally, Andrew Victor Gaiser, Timo Nagy Attila Baker, Benjamin Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Engel, Jörg B.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM033566
035-os BibID:	PMID:16182122 WOS:000232648000028
Első szerző:	Keller, Gunhild
Cím:	Receptors for luteinizing hormone releasing hormone (LHRH) expressed in human non-Hodgkin's lymphomas can be targeted for therapy with the cytotoxic LHRH analogue AN-207 / Gunhild Keller, Andrew V. Schally, Timo Gaiser, Attila Nagy, Benjamin Baker, Gabor Halmos, Jörg B. Engel
Dátum:	2005
ISSN:	0959-8049
Megjegyzések:	We determined by immunohistochemistry the presence of LHRH receptors in surgical specimens of human non-Hodgkin's lymphomas (NHL) and investigated the expression of LHRH receptors in two human NHL cell lines, RL and HT by RT-PCR, Western blot and radioligand binding studies. In in vivo experiments with nude mice bearing tumours of these NHL cell lines, the efficacy of cytotoxic LHRH analogue AN-207 and its cytotoxic radical AN-201 was examined. LHRH receptors were detected in 94.1% of the human NHL specimens and in both NHL cell lines. AN-207 significantly (P < 0.01) inhibited the growth of RL and HT tumours, while the non-targeted AN-201 had no effects. Blockade of the LHRH receptors with an excess of LHRH agonist Decapeptyl suppressed the antitumour effects of AN-207. Our findings indicate that LHRH receptors expressed in a high percentage of human NHL specimens can be used for effective targeted therapy with the cytotoxic LHRH analogue AN-207.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	European Journal of Cancer. - 41 : 14 (2005), p. 2196-2202. -
További szerzők:	Schally, Andrew Victor Gaiser, Timo Nagy Attila Baker, Benjamin Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Engel, Jörg B.
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