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1.

001-es BibID:BIBFORM033539
035-os BibID:WOS:000239069400046
Első szerző:Buchholz, Stefan
Cím:Therapy of ovarian cancers with targeted cytotoxic analogs of bombesin, somatostatin, and luteinizing hormone-releasing hormone and their combinations / Stefan Buchholz, Gunhild Keller, Andrew V. Schally, Gabor Halmos, Florian Hohla, Elmar Heinrich, Frank Koester, Benjamin Baker, Jörg B. Engel
Dátum:2006
ISSN:0027-8424
Megjegyzések:The aim of this study was to investigate the effect of treatment of experimental ovarian cancers with targeted cytotoxic analogs as single compounds and in combination. Targeted cytotoxic analogs of bombesin (AN-215), somatostatin (AN-238), and luteinizing hormone-releasing hormone (AN-207) consisted of 2-pyrrolinodoxorubicin (AN-201) linked to the respective peptide carrier. AN238 at 200 nmol/kg significantly inhibited growth of UCI-107, ES-2 and OV-1063 ovarian cancers. AN-215 alone at 200 nmol/kg and its combination with AN-238 at one-half of the dose were also able to inhibit the growth of UCI-107 tumors. A combination of AN-238 with AN-207at 50% of the dose strongly suppressed the proliferation of ES-2 and OV-1063 ovarian tumors. Cytotoxic radical AN-201 was toxic and had no significant effect on tumor growth. In contrast, the toxicity of the conjugated peptide analogs was low. Because ovarian cancers tend to acquire chemoresistance, we used real-time PCR to measure the mRNA expression of multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein after treatment. Low or no induction of multidrug resistance protein 1, multidrug resistance-related protein, and breast cancer resistance protein occurred after treatment with AN-238, AN-215, and the combination of AN-238 with AN-207 or AN-215. These results demonstrate that a therapy with cytotoxic analogs such as single agents and combinations is effective and nontoxic. Our work suggests that cytotoxic peptide analogs of luteinizing hormone-releasing hormone, somatostatin, and bombesin could be used for the therapy of ovarian cancers, considering the lack of induction of chemoresistance.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 103 : 27 (2006), p. 10403-10407. -
További szerzők:Keller, Gunhild Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Hohla, Florian Heinrich, Elmar Koester, Frank Baker, Benjamin Engel, Jörg B.
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2.

001-es BibID:BIBFORM033580
035-os BibID:PMID:15831285 WOS:000228526600008
Első szerző:Engel, Jörg B.
Cím:Effective treatment of experimental human endometrial cancers with targeted cytotoxic luteinizing hormone-releasing hormone analogues AN-152 and AN-207 / Jörg B. Engel, Gunhild Keller, Andrew V. Schally, Attila Nagy, David D. Chism, Gabor Halmos
Dátum:2005
ISSN:0015-0282
Megjegyzések:Objective: To treat experimental human endometrial cancers based on targeted chemotherapy with the cytotoxic luteinizing hormone-releasing hormone (LHRH) analogues AN-152 and AN-207. Design: Experimental study using athymic nude mice bearing xenografts of HEC-1A and RL-95-2 human endometrial cancers to assess the efficacy and toxicity of AN-152 and AN-207. The expression of LHRH receptors in HEC-1A and RL-95-2 cancers was determined by reverse transcription-polymerase chain reaction, Western blot analysis, and radioligand binding assays. Setting: Experimental laboratory research. Animal(s): Female athymic nude mice (Ncr, nu/nu). Intervention(s): Animals were treated with IV injections of the cytotoxic LHRH analogues AN-152 and AN-207 and their respective cytotoxic radicals doxorubicin (DOX) and AN-201 (2-pyrrolinodoxorubicin) on a control vehicle solution. Main Outcome Measure(s): Tumor volume, final tumor weight, tumor doubling time, body weight, white blood cell count. and LHRH receptor expression. Result(s): AN-152 significantly inhibited the growth of HEC-1A tumors. AN-207 also significantly suppressed the proliferation in vivo of HEC-1A and RL-95-2 cancers. The cytotoxic radicals DOX and AN-201 had no effect. Furthermore. mRNA for LHRH receptors, LHRH receptor protein, and high-affinity binding sites for LHRH were demonstrated on tumors. Conclusion(s): Targeted chemotherapy with AN-152 and AN-207 strongly inhibits the growth of human endometrial cancers, which express LHRH receptors, and could provide a new treatment modality for women with advanced endometrial carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Fertility and Sterility. Supplement. - 83 : Suppl. 1 (2005), p. 1125-1133. -
További szerzők:Keller, Gunhild Schally, Andrew Victor Nagy Attila Chism, David Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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3.

001-es BibID:BIBFORM033581
035-os BibID:WOS:000227770000039 PMID:15788692
Első szerző:Engel, Jörg B.
Cím:Effective inhibition of experimental human ovarian cancers with a targeted cytotoxic bombesin analogue AN-215 / Jörg B. Engel, Gunhild Keller, Andrew V. Schally, Gabor Halmos, Brian Hammann, Attila Nagy
Dátum:2005
ISSN:1078-0432
Megjegyzések:Purpose: To determine whether the cytotoxic analogue of bombesin/gastrin-releasing peptide (GRP) AN-215 can inhibit the in vivo growth of four human ovarian cancer cell lines. AN-215 consists of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin linked to a bombesin antagonist carrier des-D-Tpi-RC-3095. This conjugate binds strongly to receptors for bombesin/GRP and can be targeted to tumors that express these receptors. Bombesin/GRP receptors are found in 77% of human ovarian cancer specimens. Experimental Design: Nude mice bearing xenografts of ES-2, SKOV-3, OV-1063, and UCI-107 human ovarian carcinomas were treated with AN-215. The antitumor effects and the toxicity were determined. The expression of bombesin receptor subtypes was measured by reverse-transcriptase PCR analysis, and the presence of bombesin/GRP receptors was determined by radioligand binding assays. Results: AN-215 significantly (P < 0.05) inhibited growth of ES-2, OV-1063, and UCI-107 tumors, prevented the metastatic spread of ES-2 cancers, and prolonged the survival of nude mice bearing i.p. ES-2 xenografts. Cytotoxic radical AN-201, the unconjugated mixture of bombesin antagonist RC-3095 and AN-201 or RC-3095 alone had no significant effects. Blockade of bombesin/GPP receptors abolished the effect of AN-215. The expression of bombesin/GRP receptors was not changed after repeated treatment with AN-215. Conclusions: Our findings indicate that targeted chemotherapy with cytotoxic bombesin/GRP analogue AN-215 can inhibit ovarian tumors, which express bombesin/GRP receptors. AN-215 might provide a new treatment modality for women with advanced ovarian carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Clinical Cancer Research. - 11 : 6 (2005), p. 2408-2415. -
További szerzők:Keller, Gunhild Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Hammann, Brian Nagy Attila
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4.

001-es BibID:BIBFORM033578
035-os BibID:PMID:15784701 WOS:000229351000068
Első szerző:Engel, Jörg B.
Cím:Inhibition of growth of experimental human endometrial cancer by an antagonist of growth hormone-releasing hormone / Jörg B. Engel, Gunhild Keller, Andrew V. Schally, Gabor L. Toller, Kate Groot, Alexandre Havt, Patricia Armatis, Marta Zarandi, Jozsef L. Varga, Gabor Halmos
Dátum:2005
ISSN:0021-972X
Megjegyzések:Antagonists of GHRH are being developed for the treatment of various cancers. In this study we investigated in vivo and in vitro the effects of the GHRH antagonist MZ-J-7-118 and its mechanism of action in HEC-1A human endometrial cancer. Treatment of nude mice bearing HEC-1A xenografts with 10 mug/d MZ-J-7-118 for 6 wk significantly inhibited the volume of HEC-1A tumors by 43%, tumor weight by 40% compared with controls and prolonged the tumor doubling time from 18.7 +/- 1.4 to 25.4 +/- 3.8 d. Administration of 20 mug MZ-J-7-118, sc, twice a day significantly (P < 0.05) decreased HEC-1A growth, as evidenced by a 57.9% decrease in tumor volume, a 50.7% reduction in tumor weight, and the extension of tumor doubling time from 17.5 +/- 2.8 to 36.4 +/- 6.5 d. Therapy with GHRH antagonists significantly decreased serum IGF-I levels in experiment 1, and significantly increased tumoral IGF-I levels in experiment 2 in treated mice. Levels of IGF-II and vascular endothelial growth factor-A in tumors were not changed. Specific high affinity binding sites for GHRH were found on HEC-1A tumor membranes using ligand competition assays with (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-118 displaced radiolabeled JV-1-42 with an IC(50) of 0.13 +/- 0.04 nm. The expression of mRNA for GHRH and splice variants of the GHRH receptor in HEC-1A tumors was demonstrated by real-time RT-PCR analysis. HEC-1A cells cultured in vitro secreted GHRH into the medium. The GHRH antagonist MZ-J-7-118 inhibited the growth of HEC-1A cells in vitro. Our results indicate that GHRH antagonists can reduce the growth of human endometrial cancer and could be used as an alternative adjuvant therapy for the management of endometrial cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal Of Clinical Endocrinology & Metabolism. - 90 : 6 (2005), p. 3614-3621. -
További szerzők:Keller, Gunhild Schally, Andrew Victor Toller Gábor L. Groot, Kate Havt, Alexandre Armatis, Patricia Zarándi Márta Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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5.

001-es BibID:BIBFORM033570
035-os BibID:PMID:16051478 WOS:000231891900035
Első szerző:Engel, Jörg B.
Cím:Experimental therapy of human endometrial cancers with a targeted cytotoxic bombesin analog AN-215 : low induction of multidrug resistance proteins / Jörg B. Engel, Andrew V. Schally, Gabor Halmos, Benjamin Baker, Attila Nagy, Gunhild Keller
Dátum:2005
ISSN:0959-8049
Megjegyzések:In this study we have investigated the efficacy and toxicity of targeted cytotoxic bombesin (BN) analog AN-215 and its effects on the expression of three multidrug resistance proteins in experimental human endometrial cancers. Nude mice bearing HEC-1A, RL-95-2 and AN3CA tumours were treated with AN-215 and its cytotoxic radical (AN-201). The BN receptor expression in tumours was followed by RT-PCR analysis and radioligand binding assays. Expression of drug resistance proteins MDR-1, MRP-1 and BCRP were measured by realtime PCR. AN-215 significantly (P<0.05) inhibited the growth of HEC-1A, RL-95-2 and AN3CA tumours while AN-201 was ineffective. The expression of BN receptors was demonstrated in all three tumour models. AN-215 caused a lower induction of MDR-1 in HEC-1A and RL-95-2 cancers than AN-201. MRP-1 and BCRP were not induced by AN-215 or AN-201. Thus, targeted chemotherapy with AN-215 powerfully inhibits the growth of human BN receptor-positive endometrial cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:European Journal Of Cancer. - 41 : 12 (2005), p. 1824-1830. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Baker, Benjamin Nagy Attila Keller, Gunhild
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6.

001-es BibID:BIBFORM033564
035-os BibID:WOS:000231743700023 PMID:16047355
Első szerző:Engel, Jörg B.
Cím:Targeted therapy with a cytotoxic somatostatin analog, AN-238, inhibits growth of human experimental endometrial carcinomas expressing multidrug resistance protein MDR-1 / Jorg B. Engel, Andrew V. Schally, Gabor Halmos, Ben Baker, Attila Nagy, Gunhild Keller
Dátum:2005
ISSN:0008-543X
Megjegyzések:BACKGROUND. Chemoresistance mediated by membrane transporters such as multidrug resistance (MDR-1) glycoprotein remains a challenge in the chemotherapy treatment of advanced or recurrent endometrial carcinoma. Targeted chemotherapy might overcome this resistance. The cytotoxic somatostatin (SST) analog, AN-238, consists of a superactive derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201), linked to the SST analog carrier, RC-121. This conjugate binds strongly to SST receptor subtypes (sst) 2a (sst2(a)) and 5 (sst(5)) and can be targeted to tumors that express these receptors. METHODS. The presence of sst2(a) and sst, was determined in 3 human endometrial carcinoma cell lines (HEC-1A, RL-95-2, and AN3CA). Nude mice bearing xenografts of these cancers were treated with AN-238 and its radical, AN-201. The antitumor effects and toxicity were compared. The authors studied the effects of AN-238 and AN-201 on the expression levels of MDR-1, multidrug resistance related protein (MRP-1), and breast carcinoma resistance protein (BCRP) by real-time polymerase chain reaction. RESULTS. The authors demonstrated the presence of mRNA and receptor protein for sst2(a) and sst, on HEC-1A, RL-95-2, and AN3CA tumors. AN-238 significantly (P < 0.05) inhibited the growth of these tumors, whereas AN-201 had no effect. Blockade of SST receptors nullified the effects of AN-238. In all 3 endometrial carcinoma lines, AN-238 caused a weaker induction of MDR-1 than AN-201. No major induction of MRP-1 and BCRP occurred after treatment with AN-238 or AN-201. CONCLUSIONS. Targeted chemotherapy with the cytotoxic SST analog, AN-238, inhibited powerfully the growth of endometrial carcinoma, which express SST receptors, regardless of their expression level of MDR-1.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer. - 104 : 6 (2005), p. 1312-1321. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Baker, Benjamin Nagy Attila Keller, Gunhild
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7.

001-es BibID:BIBFORM033554
035-os BibID:WOS:000234215800022 PMID:16322338
Első szerző:Engel, Jörg B.
Cím:Targeted cytotoxic bombesin analog AN-215 effectively inhibits experimental human breast cancers with a low induction of multi-drug resistance proteins / Jörg B. Engel, Andrew V. Schally, Gabor Halmos, Benjamin Baker, Attila Nagy, Gunhild Keller
Dátum:2005
ISSN:1351-0088
Megjegyzések:The cytotoxic analog of bombesin (BN)/gastrin releasing peptide (GRP) AN-215 consisting of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin linked to a bombesin analog carrier, displays a high affinity to BN/GRP receptors and can be targeted to tumors that express these receptors. We evaluated the antitumor effect and the toxicity of AN-215 in 5 human breast cancer cell lines xenografted into nude mice. In addition, we measured the mRNA expression of multi drug resistance protein 1 (MDR-1), multi drug resistance related protein 1 (MRP-1) and breast cancer resistance protein (BCRP) by real-time PCR analysis after treatment with AN-215. All five cell lines expressed BN/GRP receptors, and AN-215 significantly (P<0.05) inhibited tumor growth in all models, while its cytotoxic radical AN-201 had no significant effect in four models. In MX-1 tumors, AN-201 had a significantly weaker antitumor effect than AN-215. The effect of AN-215 was nullified by a blockade of BN/GRP receptors with a bombesin antagonist. Low or no induction of MDR-1, MRP-1 and BCRP occurred after treatment with AN-215. In conclusion, targeted chemotherapy with the cytotoxic BN/GRP analog AN-215 strongly inhibits breast cancers that express BN/GRP receptors and might provide a new treatment modality for mammary carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrine-Related Cancer. - 12 : 4 (2005), p. 999-1009. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Baker, Benjamin Nagy Attila Keller, Gunhild
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8.

001-es BibID:BIBFORM033579
035-os BibID:PMID:15609311 WOS:000227535600018
Első szerző:Keller, Gunhild
Cím:Growth inhibition of experimental non-Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN-238 / Gunhild Keller, Jörg B. Engel, Andrew V. Schally, Attila Nagy, Brian Hammann, Gabor Halmos
Dátum:2005
ISSN:0020-7136
Megjegyzések:The cytotoxic analogue of somatostatin, AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin (DOX), linked to somatostatin analogue carrier RC-121 binds with high affinity to receptors for somatostatin and can be targeted to tumors that express these receptors. Because somatostatin receptors are found in a high percentage of human non-Hodgkin's lymphomas (NHLs), we evaluated the antitumor effect of AN-238 in 2 human NHL cell lines in vivo. Nude mice bearing xenografts of RL and HT human NHL were treated with AN-238 or its components at equimolar doses, and antitumor effects were determined. Expression of mRNA for somatostatin receptor subtypes was measured by RT-PCR, and the presence of somatostatin receptors was determined by radioligand binding. Toxicity was evaluated by following white blood cell count (WBC) and body weight. AN-238 significantly (p < 0.05) inhibited growth of RL and HT xenografts and prolonged the tumor doubling time. Cytotoxic radical AN-201, the unconjugated mixture of somatostatin analogue RC-121 and AN-201 or RC-121 alone had no significant effects. Blockade of somatostatin receptors by excess RC-121 abolished the effect of AN-238, demonstrating targeting. Expression of somatostatin receptors was not changed after repeated treatment with AN-238. AN-201, but not AN-238, significantly lowered the WBC and caused a greater decrease in body weight than AN-238. Our findings demonstrate that targeted chemotherapy with AN-238 can strongly inhibit the growth of NHL cells, which express somatostatin receptors. AN-238 could be considered for the treatment for patients with NHL.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:International Journal of Cancer. - 114 : 5 (2005), p. 831-835. -
További szerzők:Engel, Jörg B. Schally, Andrew Victor Nagy Attila Hammann, Brian Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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9.

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.
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10.

001-es BibID:BIBFORM033573
035-os BibID:PMID:16027368 WOS:000230853300041
Első szerző:Keller, Gunhild
Cím:Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone / Gunhild Keller, Andrew V. Schally, Kate Groot, Gabor L. Toller, Alexandre Havt, Frank Köster, Patricia Armatis, Gabor Halmos, Marta Zarandi, Jozsef L. Varga, Jörg B. Engel
Dátum:2005
ISSN:0027-8424
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) were shown to inhibit the growth of various cancers. We investigated the antitumor activity and the mechanism of action of GHRH antagonists in human non-Hodgkin's lymphomas (NHL). Nude mice bearing xenografts of RL and HT human NHL were treated with GHRH antagonists MZ-5-156 and MZ-J-7-138 at a dose of 40 microg twice daily. The concentrations of serum IGF-1 and GHRH, bFGF, and VEGF in tumor tissue were measured by radioimmunoassays. Expression of GHRH and splice variant 1 of the GHRH receptor in both cell lines was examined by RT-PCR. The effects of MZ-5-156, MZ-J-7-138 and GHRH on cell proliferation were evaluated in vitro. Treatment with MZ-5-156 and MZ-J-7-138 significantly (P < 0.05) inhibited the growth of RL and HT tumors by 59.9-73.9%. High-affinity binding sites for GHRH and mRNA for GHRH and splice variant-1 of the GHRH receptors were found on RL and HT tumors. RL and HT cells contained GHRH peptide, and their growth in vitro was significantly inhibited by both antagonists. IGF-I levels in serum of mice were significantly decreased by antagonist MZ-5-156. Therapy with GHRH antagonists also significantly reduced tumoral bFGF, whereas VEGF levels were not suppressed. Our findings suggest that GHRH antagonists inhibit the growth of RL and HT lymphomas by direct effects mediated by tumoral receptors for GHRH. GHRH antagonists could offer a new therapeutic modality for the management of advanced NHL.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States Of America. - 102 : 30 (2005), p. 10628-10633. -
További szerzők:Schally, Andrew Victor Groot, Kate Toller Gábor L. Havt, Alexandre Köster, Frank Armatis, Patricia Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Zarándi Márta Varga József L. Engel, Jörg B.
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11.

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.
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12.

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.
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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