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1.

001-es BibID:BIBFORM033618
035-os BibID:WOS:000089931600051 PMID:11051271
Első szerző:Chatzistamou, Ioulia
Cím:Effective treatment of metastatic MDA-MB-435 human estrogen-independent breast carcinomas with a targeted cytotoxic analogue of luteinizing hormone-releasing hormone AN-207 / Ioulia Chatzistamou, Andrew V. Schally, Attila Nagy, Patricia Armatis, Karoly Szepeshazi, Gabor Halmos
Dátum:2000
Megjegyzések:A highly potent derivative of doxorubicin, 2-pyrrolinod-oxorubicin (AN-201), was linked to [D-Lys(6)]luteinizing hormone-releasing hormone (LH-RH) to form a cytotoxic analogue, AN-207, that can be targeted to LH-RT-I receptors, The effects of AN-207 were investigated in MDA-MB-435 human estrogen-independent breast carcinomas, which express LB-RH receptors, In experiment I, nude mice bearing orthotopically implanted tumors received a single i.v. injection of AN-207, AN-201, or the carrier at 250 nmol/kg, Five weeks after administration of AN-207, tumor volume was significantly decreased by 66% (P < 0.001) and tumor burden by 71% (P < 0.05) as compared with controls, but no significant effects occurred in other groups. Six of eight (75%) control animals and 37.5% of mice treated with AN-201 developed metastases in the lymph nodes, whereas no lymphatic spread was found in any of the mice that received injections of AN-207, The antitumor effect of AN-207 could be partially blocked by pretreatment of the tumor-bearing mice with high doses of agonist [D-Trp(6)]LH-RH,which suggests that AN-207 acts on LH-RH receptors on tumors. The mortality due to toxicity was 25% in the group receiving AN-201 and 12.5% in the AN-207-treated group. Radioligand binding assays revealed the presence of high-affinity binding sites for LH-RH on tumor membranes, and mRNA for LH-RH receptors was demonstrated by reverse transcription-PCR, In experiment 2, two i.v. injections of AN-207 or AN-201 at 150 nmol/kg were given on days 0 and 28 to mice bearing orthotopic xenografts of MDA-MB-435, The outcome of the treatment was similar to that observed in experiment 1, but without any toxicity-related deaths, Tumor growth inhibition and prevention of metastatic disease suggest that cytotoxic LH-RH analogue AN-207 could be considered for the treatment of human estrogen-independent breast cancers expressing receptors for LH-RH.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Clinical Cancer Research. - 6 : 10 (2000), p. 4158-4165. -
További szerzők:Schally, Andrew Victor Nagy Attila Armatis, Patricia Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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2.

001-es BibID:BIBFORM033557
035-os BibID:WOS:000233762000030
Első szerző:Havt, Alexandre
Cím:The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues / Alexandre Havt, Andrew V. Schally, Gabor Halmos, Jozsef L. Varga, Gabor L. Toller, Judit E. Horvath, Karoly Szepeshazi, Frank Köster, Kevin Kovitz, Kate Groot, Marta Zarandi, Celia A. Kanashiro
Dátum:2005
ISSN:0027-8424
Megjegyzések:Various attempts to detect human pituitary growth hormone-releasing hormone receptor (pGHRH-R) in neoplastic extrapituitary tissues have thus far failed. Recently, four splice variants (SVs) of GHRH-R have been described, of which SV1 has the highest structural homology to pGHRH-R and likely plays a role in tumor growth. The aim of this study was to reinvestigate whether human tumors and normal human extrapituitary tissues express the pGHRH-R and to corroborate our previous findings on its SVs. Thus, we developed a real-time PCR method for the detection of the mRNA for the pGHRH-R, its SVs, and the GHRH peptide. Using real-time PCR, Western blotting, and radioligand-binding assays, we detected the mRNA for pGHRH-R and pGHRH-R protein in various human cancer cell lines grown in nude mice and in surgical specimens of human lung cancers. The expression of mRNA for SVs of pGHRH-R and GHRH was likewise found in xenografts of human non-Hodgkin's lymphomas, pancreatic cancer, glioblastoma, small-cell lung carcinomas, and in human nonmalignant prostate, liver, lung, kidney, and pituitary. Western blots showed that these normal and malignant human tissues contain SV1 protein and immunoreactive GHRH. Our results demonstrate that some normal human tissues and tumors express mRNA and protein for the pGHRH-R and its splice variants. These findings confirm and extend the concept that GHRH and its receptors play an important role in the pathophysiology of human cancers.
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 : 48 (2005), p. 17424-17429. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Varga József L. Toller Gábor L. Horváth Judit E. (New Orleans) Szepesházi Károly Köster, Frank Kovitz, Kevin Groot, Kate Zarándi Márta Kanashiro, Celia A.
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3.

001-es BibID:BIBFORM033538
035-os BibID:WOS:000240968100047
Első szerző:Hohla, Florian
Cím:Synergistic inhibition of growth of lung carcinomas by antagonists of growth hormone-releasing hormone in combination with docetaxel / Florian Hohla, Andrew V. Schally, Karoly Szepeshazi, Jozsef L. Varga, Stefan Buchholz, Frank Köster, Elmar Heinrich, Gabor Halmos, Ferenc G. Rick, Chandrika Kannadka, Christian Datz, Celia A. Kanashiro
Dátum:2006
ISSN:0027-8424
Megjegyzések:We investigated the effect of antagonists of growth hormone-releasing hormone (GHRH) MZ-J-7-138 and JV-1-92 on H460 human non-small cell lung carcinoma (NSCLC) xenografted orthotopically into nude mice. Treatment with MZ-J-7-138 or JV-1-92 inhibited orthotopic growth of H460 NSCLC by 52-65% (P < 0.001) and was associated with a significant decrease in protein expression of K-Ras, cyclooxygenase-2 (Cox-2) and phospho-Akt (pAkt). in other experiments, treatment with MZ-J-7-138 or docetaxel reduced tumor volume of s.c. xenografted H460 human NSCLC by 30-36% (P < 0.01). The combination of MZ-J-7-138 and docetaxel resulted in a synergistic growth inhibition of H460 NSCLC xenografts of 63%. MZ-J-7-138 alone or in combination with docetaxel significantly reduced protein levels of K-Ras, Cox-2, and pAkt by 56-63%. Docetaxel given singly diminished the protein levels only of Cox-2 and did not affect K-Ras and pAkt. High-affinity binding sites, mRNA, and protein expression of pituitary GHRH receptors and its splice variant (SV) 1 were found in H460. H460 NSCLC cells contained GHRH peptide, and its growth was significantly inhibited in vitro by 10 mu M MZ-J-7-138 (P < 0.001). Serum insulin-like growth factor 1 (IGF1) was not reduced by either GHRH antagonists. These findings suggest that antiproliferative effects of GHRH antagonists in H460 NSCLC are associated with down-regulation of K-Ras, Cox-2, and pAkt. In conclusion, GHRH antagonists in combination with docetaxel synergistically inhibit growth of H460 NSCLC and the expression of K-ras, Cox-2, and pAkt, which might abrogate the signal transduction pathways for cell growth stimulation and therapeutic resistance.
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 : 39 (2006), p. 14513-14518. -
További szerzők:Schally, Andrew Victor Szepesházi Károly Varga József L. Buchholz, Stefan Köster, Frank Heinrich, Elmar Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Rick Ferenc G. Kannadka, Chandrika Datz, Christian Kanashiro, Celia A.
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4.

001-es BibID:BIBFORM033812
035-os BibID:PMID:21533457 WOS:A1997WW11900001
Első szerző:Jungwirth, Andreas
Cím:Regression of rat Dunning R-3327-H prostate carcinoma by treatment with targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 containing 2-pyrrolinodoxorubicin / Andreas Jungwirth, Andrew V. Schally, Attila Nagy, Jacek Pinski, Kate Groot, Georg Galvan, Karoly Szepeshazi, Gabor Halmos
Dátum:1997
Megjegyzések:The effects of AN-207, a new targeted cytotoxic analog of LH-RH, were evalued in rats bearing hormone-dependent Dunning R-3327-H prostate carcinomas. AN-207 consists of the agonist [D-Lys(6)]LH-RH linked to 2-pyrrolino-doxorubicin, an intensely potent derivative of doxorubicin. In the first experiment, 2-pyrrolinodoxorubicin was administered at a concentration of 50 nmol/kg, as a single drug (AN-201) and as an unconjugated mixture with [D-Lys(6)]LH-RH or conjugated to the carrier [D-Lys(6)]LH-RH (AN-207). Following the second administration of radical AN-201 alone or mixed with the carrier, all rats died with signs of general toxicity, but all animals treated with the conjugate AN-207, survived. After 5 weeks of treatment with a total dose of 150 nmol/kg AN-207, the tumors regressed from an initial volume of 8.35 +/- 1.7 cm(3) to 4.47 +/- 0.8 cm(3), while tumors in the control group measured 17.84 +/- 2.2 cm(3). The therapy with AN-207 also significantly reduced tumor weight and tumor burden. In the second experiment, we compared the efficacy and toxicity of 3 injections of 25 nmol/kg AN-201 or 25 nmol/kg and 50 nmol/kg AN-207. The initial tumor volume in all groups was between 3.9 and 4.5 cm(3). After 5 weeks of therapy, the tumors of rats treated with 50 nmol/kg AN-207 regressed to 2.3 +/- 0.51 cm(3), whereas 25 nmol/kg AN-201 was still toxic in contrast to 25 nmol/kg AN-207, while the reduction in final tumor volume was similar (6.76 +/- 1.4 cm(3) and 6.74 +/- 1 cm(3), respectively), as compared to 15.6 +/- 2.2 cm(3) for untreated animals. High capacity LH-RH receptors were found in the membranes of untreated Dunning tumor specimens, but after treatment with AN-207, they could no longer be detected. This is the first demonstration that the new targeted cytotoxic LH-RH analog AN-207 is an effective antitumor agent. Our work indicates that the cytotoxic analog AN-207 is much less toxic than the antineoplastic radical (AN-201) incorporated, and significantly more active in inhibiting tumor growth. Further development of approaches based on targeted cytotoxic analog AN-207 may lead to major improvements in current palliative therapy of prostate cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:International journal of oncology. - 10 : 5 (1997), p. 877-884. -
További szerzők:Schally, Andrew Victor Nagy Attila Pinski, Jacek Groot, Kate Galvan, Georg Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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5.

001-es BibID:BIBFORM033753
035-os BibID:WOS:000073081500755
Első szerző:Jungwirth, Andreas
Cím:Somatostatin analog RC-160, LH-RH antagonist cetrorelix and bombesin antagonist RC-3940-II inhibit growth of Caki-1 human renal carcinoma / Jungwirth A., Frick J., Schally A. V., Halmos G., Groot K., Szepeshazi K., Pinski J.
Dátum:1998
ISSN:0022-5347
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idézhető absztrakt
Megjelenés:Journal of Urology. Supplement S. - 159 : 5 (1998), 189. p. -
További szerzők:Frick, Julian Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Szepesházi Károly Pinski, Jacek
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6.

001-es BibID:BIBFORM033689
035-os BibID:PMID:9254895 WOS:A1997XN99200002
Első szerző:Jungwirth, Andreas
Cím:Luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) and bombesin antagonist RC-3940-II inhibit the growth of androgen-independent PC-3 prostate cancer in nude mice / Andreas Jungwirth, Georg Galvan, Jacek Pinski, Gabor Halmos, Karoly Szepeshazi, Ren-Zhi Cai, Kate Groot, Andrew V. Schally
Dátum:1997
ISSN:0270-4137
Megjegyzések:BACKGROUND: Hormones like bombesin (BN)/gastrin-releasing peptide (GRP) and luteinizing hormone-releasing hormone (LH-RH) and growth factors such as epidermal growth factor (EGF) might be involved in the relapse of prostate cancer under androgen ablation therapy. Interference with receptors for BN/GRP, LH-RH, or EGF might provide a therapeutic approach to inhibit tumor growth of androgen-independent prostate cancer. METHODS: LH-RH antagonist Cetrorelix (SB-75) and the BN/GRP antagonist RC-3940-II were tested for their effects on the growth of the androgen-independent PC-3 human prostate cancer cell line xenografted into nude mice. Tumor growth, serum hormone levels, and receptor concentrations for BN/GRP and EGF were measured. RESULTS: When the treatment was started, tumor volume in all groups was 70-80 mm3. After 4 weeks, tumor volume in the control animals injected with saline was 871 +/- 233 mm3 and that of animals treated with Cetrorelix only 197 +/- 61 mm3. The BN/GRP antagonist RC-3940-II also significantly reduced PC-3 tumor volume in nude mice to 122 +/- 20 mm3. The combination of Cetrorelix and RC-3940-II produced no additional inhibition. High-affinity receptors for EGF were detected in the tumor membranes and their number was significantly decreased after administration of Cetrorelix or RC-3940-II. CONCLUSIONS: These findings demonstrate that LH-RH antagonists and BN/GRP antagonists inhibit the growth of the androgen-independent prostate cancer cell line PC-3 in vivo. Both analogs may exert a direct inhibitory effect on tumor growth through a down-regulation of EGF receptors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Prostate. - 32 : 3 (1997), p. 164-172. -
További szerzők:Galvan, Georg Pinski, Jacek Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Cai, Ren-Zhi Groot, Kate Schally, Andrew Victor
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7.

001-es BibID:BIBFORM033687
035-os BibID:WOS:A1997XJ25000027
Első szerző:Jungwirth, Andreas
Cím:Inhibition of growth of androgen-independent DU-145 prostate cancer in vivo by luteinising hormone-releasing hormone antagonist Cetrorelix and bombesin antagonists RC-3940-II and RC-3950-II / A. Jungwirth, J. Pinski, G. Galvan, G. Halmos, K. Szepeshazi, R. Z. Cai, K. Groot, M. Vadillo-Buenfil, A. V. Schally
Dátum:1997
ISSN:0959-8049
Megjegyzések:The aim of this study was to test the antagonist of LH-RH (Cetrorelix), agonist [D-Trp6]LH-RH (triptorelin) and new bombesin antagonists RC-3940-II and RC-3950-II for their effect on the growth of an androgen-independent prostate cancer cell line, DU-145, xenografted into nude mice. Xenografts were grown in male nude mice, and after 4 weeks, the animals were treated either with saline (control) or with one of the analogues. One group of mice was given a combination of Cetrorelix and RC-3950-II. Treatment was given for 4 weeks. Tumour and body weights, and tumour volumes were measured. At sacrifice, tumours were dissected for histological examination and receptor studies. Serum was collected for measurement of hormone levels. The final tumour volume in control animals injected with saline was 577 +/- 155 mm3 and that of animals treated with Cetrorelix only 121.4 +/- 45 mm3 (P < 0.01). Bombesin antagonists RC-3940-II and RC-3950-II also significantly reduced DU-145 tumour volume in nude mice to 84.9 +/- 19.9 and 96.8 +/- 28 mm3, respectively. Agonist [D-Trp6]LH-RH did not significantly inhibit tumour growth. Serum levels of LH were decreased to 0.08 +/- 0.02 ng/ml (P < 0.05) in the Cetrorelix treated group as compared to 1.02 +/- 0.1 ng/ml for the controls, and testosterone levels were reduced to castration levels (0.01 +/- 0.01 ng/ml). Specific receptors for EGF and LH-RH in DU-145 tumours were significantly downregulated after treatment with Cetrorelix, RC-3940-II and RC-3950-II. Although LH-RH could be a local regulator of growth of prostate cancer, the fall in LH-RH receptors is not fully understood and the inhibitory effects of Cetrorelix and bombesin antagonists on DU-145 tumour growth might be attributed at least in part to a downregulation of EHF receptors. Since Cetrorelix and bombesin antagonists inhibit growth of androgen-independent DU-145 prostate cancers, these compounds could be considered for the therapy of advanced prostate cancer in men, especially after relapse.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:European Journal of Cancer. - 33 : 7 (1997), p. 1141-1148. -
További szerzők:Pinski, Jacek Galvan, Georg Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Cai, Ren-Zhi Groot, Kate Vadillo-Buenfil, Manuel Schally, Andrew Victor
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8.

001-es BibID:BIBFORM033669
035-os BibID:PMID:9486581 WOS:000072146700016
Első szerző:Jungwirth, Andreas
Cím:Inhibition of the growth of Caki-I human renal adenocarcinoma in vivo by luteinizing hormone-releasing hormone antagonist Cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II / Andreas Jungwirth, Andrew V. Schally, Gabor Halmos, Kate Groot, Karoly Szepeshazi, Jacek Pinski, Patricia Armatis
Dátum:1998
ISSN:0008-543X
Megjegyzések:BACKGROUND: Metastatic or recurrent renal cell carcinoma (RCC) is a therapeutic challenge because it is resistant to chemotherapy and external radiotherapy. No uniformly effective therapeutic agents are available for the management of patients with RCC. Hormones and growth factors may play a role in promoting the transformation and/or proliferation of kidney neoplasms. METHODS: Luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix (SB-75), somatostatin analog RC-160, and bombesin antagonist RC-3940-II were tested for their effects on the growth of the Caki-I renal adenocarcinoma cell line xenografted into nude mice. RESULTS: After 4 weeks of treatment, tumor volume was significantly (P < 0.01) decreased in animals receiving RC-160, to 167.5 +/- 34.2 mm3, compared with the control group (485.7 +/- 77.2 mm3). LH-RH antagonist SB-75 and bombesin antagonist RC-3940-II also significantly reduced the volume of Caki-I tumors, to 159.9 +/- 18.1 and 234.7 +/- 81.8 mm3, respectively. Somatostatin analog RC-160 decreased serum levels for growth hormone (GH) and insulin-like growth factor-I compared with controls. Treatment with RC-160, Cetrorelix, and RC-3940-II significantly reduced the number of high-affinity receptors for epidermal growth factor on Caki-I tumors. CONCLUSIONS: LH-RH antagonist Cetrorelix, somatostatin analog RC-160, and bombesin antagonist RC-3940-II effectively inhibit the growth of human Caki-I renal adenocarcinomas in nude mice. These peptide analogs should be considered for the therapy of patients with metastatic or recurrent RCC.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer. - 82 : 5 (1998), p. 909-917. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Szepesházi Károly Pinski, Jacek Armatis, Patricia
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9.

001-es BibID:BIBFORM033617
035-os BibID:WOS:000168134500023
Első szerző:Kiaris, Hippokratis
Cím:A targeted cytotoxic somatostatin (SST) analogue, AN-238, inhibits the growth of H-69 small-cell lung carcinoma (SCLC) and H-157 non-SCLC in nude mice / H. Kiaris, A. V. Schally, A. Nagy, K. Szepeshazi, F. Hebert, G. Halmos
Dátum:2001
ISSN:0959-8049
Megjegyzések:Recently. we developed a cytotoxic analogue of somatostatin (SST), AN-238, in which the SST carrier peptide RC-121 was linked to 2-pyrrolinodoxorubicin (2-pyrrolino-DOX) (AN-201), a potent derivative of doxorubicin. AN-238 can be targeted to SST receptors (SSTRs) on tumours. In the present study, we evaluated the effects of AN-238 on the growth of H-69 small-cell lung carcinoma (SCLC) and H-157 non-SCLC xenografted into nude mice. High affinity binding sites for SST are present in H-69 SCLC and were now detected in H-157 non-SCLC xenografts, but not in H-157 cells. A strong expression of the human SSTR subtype 2 (hSSTR-2) and a weaker expression of subtype 5 (hSSTR-5) was found in H-69 SCLC cells, but not in H-157 non-SCLC cells. However, a strong expression of mRNA for mouse (m)SSTR-2 could be detected in H-157 xenografts. AN-238 effectively inhibited the growth of H-69 SCLC tumours in nude mice. Twenty-six days after a single injection of AN-238 at 200 nmol/kg. the volume of H-69 rumours was decreased by approximately 55% (P < 0.05) compared with the controls, while AN-201 at the same dose was highly toxic and produced only a minor tumour inhibition. To evaluate the potency of multiple doses of AN-238, nude mice bearing H-69 SCLC received three injections of AN-238 at 150 nmol/kg on days 1, 12 and 28. In the period of 42 days after the first injection, the growth rate of H-69 tumours was approximately 50% lower than that of controls. In nude mice bearing H-157 non-SCLC tumours. a single i.v. administration of AN-238 at 200 nmol/kg inhibited tumour volume by 91% after 28 days (P < 0.01 compared with controls). AN-201 was toxic and ineffective at the same dose. Two injections of AN-238 at 150 nmol/kg given on days 1 and 18 produced 83% inhibition of H-157 tumour growth (P < 0.01 versus controls). AN-238 given as a single dose of 200 nmol/kg induced necrosis. while two injections of 150 nmol/kg induced apoptosis in the tumour tissue. Our results indicate that targeted cytotoxic SST analogue AN-238 could he considered for therapy of both SCLC and non-SCLC.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:European Journal of Cancer. - 37 : 5 (2001), p. 620-628. -
További szerzők:Schally, Andrew Victor Nagy Attila Szepesházi Károly Hebert, Francine Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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10.

001-es BibID:BIBFORM033655
Első szerző:Kiaris, Hippokratis
Cím:Regression of U-87 MG human glioblastomas in nude mice after treatment with a cytotoxic somatostatin analog AN-238 / Hippokratis Kiaris, Andrew V. Schally, Attila Nagy, Baodong Sun, Karoly Szepeshazi, Gabor Halmos
Dátum:2000
Megjegyzések:Receptors for somatostatin (SST) found on brain tumors could be used for targeting of chemotherapeutic agents. This study was conducted to investigate the effects of targeted cytotoxic SST analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201), a potent derivative of doxorubicin (DOX) linked to somatostatin analogue RC-121, on the growth of SST receptor-positive U-87 MG human glioblastomas. Nude mice bearing U-87 MG xenografts received i.v. saline or equimolar doses of AN-238 or AN-201 (150 nmol/kg). Experiments also included groups that were administered RC-121 prior to the injection of AN-238, and groups injected with AN-162, a cytotoxic SST analogue similar to AN-238 but containing DOX instead of AN-201. Tumor volume, weight, and burden were determined. The effect of AN-238 and AN-201 on the survival time of nude mice bearing orthotopically implanted U-87 MG tumors was also evaluated. The binding of AN-238 to U-87 MG tumors was determined by radioreceptor assay and SST receptor (SSTR) subtype by reverse transcription-PCR. Nineteen days after a single administration of AN-238 the growth of U-87 MG tumors in nude mice was significantly inhibited (P = 0.00168), whereas two injections of AN-238 produced the regression of tumors (P = 0.0046). AN-201 was toxic and ineffective at the same dose. The antitumor effect on AN-238 could be blocked by pretreatment of the tumor-bearing mice with RC-121. The mean survival time of nude mice inoculated orthotopically with U-87 MG cells into the brain was significantly prolonged by treatment with AN-238 (P = 0.0099). AN-162 failed to inhibit significantly the growth of U-87 MG xenografts. High affinity binding sites for SST and mRNA for SST-2 receptor subtype were detected in U-87 MG tumors. Cytotoxic SST analogue AN-238 can be targeted to SST receptors on U-87 MG human glioblastomas to produce powerful inhibition of growth.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Clinical Cancer Research. - 6 : 2 (2000), p. 709-717. -
További szerzők:Schally, Andrew Victor Nagy Attila Sun, Baodong Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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11.

001-es BibID:BIBFORM033597
035-os BibID:PMID:14555524 WOS:000185830700028
Első szerző:Letsch, Markus
Cím:Preclinical evaluation of targeted cytotoxic luteinizing hormone-releasing hormone analogue AN-152 in androgen-sensitive and insensitive prostate cancers / Markus Letsch, Andrew V. Schally, Karoly Szepeshazi, Gabor Halmos, Attila Nagy
Dátum:2003
Megjegyzések:To improve conventional chemotherapy, we developed cytotoxic analogues of luteinizing hormone-releasing hormone (LH-RH), which can be targeted to prostate cancers expressing LH-RH receptors. In view of pending clinical trials on cytotoxic LH-RH analogue AN-152, containing doxorubicin (DOX) linked to [D-Lys(6])-LH-RH, we investigated the effects of AN-152 on tumor growth of s.c. implanted androgen-sensitive LNCaP and MDA-PCa-2b prostate cancers, as well as androgen-independent C4-2 prostate cancers xenografted into the tibiae of nude mice. In the C4-2 study, serum prostate-specific antigen (PSA) levels were also measured. LH-RH receptors were analyzed by reverse transcription-PCR and ligand competition assay. We also evaluated whether AN-152 can affect mRNA expression of human epidermal growth factor receptor and HER-2 and -3 oncogenes RESULTS: After 32 days of treatment with AN-152, the growth of LNCaP cancers in castrated nude mice was strongly inhibited by 83% versus intact controls (P < 0.01) and 62% versus castrated controls (P < 0.05). In animals bearing MDA-PCa-2b prostate cancers, therapy with AN-152 for 25 days resulted in a 69% inhibition of tumor growth (P < 0.01 versus controls) and was more effective (P < 0.05) than equimolar doses of DOX or microcapsules of LH-RH agonist Decapeptyl. In nude mice bearing intraosseous C4-2 prostate cancers, treatment with AN-152 decreased serum PSA levels (P < 0.01) to 10.3 +/- 3.4 ng/ml from 24.8 +/- 4 ng/ml in controls, whereas DOX had no effect on PSA. The inhibitory effects of AN-152 on C4-2 tumors was accompanied by an increase in apoptosis and a decrease in tumor proliferation. Binding sites for LH-RH and the expression of mRNA for LH-RH receptors were found on s.c. C4-2 and MDA-PCa-2b tumors. The inhibition of MDA-PCa-2b tumors by AN-152 was associated with a significant decrease in mRNA expression for epidermal growth factor receptor, HER-2, and 3. CONCLUSIONS: Our findings suggest that cytotoxic analogue AN-152 could be considered for therapeutic trials in patients with advanced prostate carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Clinical Cancer Research. - 9 : 12 (2003), p. 4505-4513. -
További szerzők:Schally, Andrew Victor Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nagy Attila
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM033594
035-os BibID:PMID:14713852 WOS:000188319300109
Első szerző:Letsch, Markus
Cím:Effective treatment of experimental androgen sensitive and androgen independent intraosseous prostate cancer with targeted cytotoxic somatostatin analogue AN-238 / Markus Letsch, Andrew V. Schally, Karoly Szepeshazi, Gabor Halmos, Attila Nagy
Dátum:2004
ISSN:0022-5347
Megjegyzések:The targeted cytotoxic somatostatin analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to carrier octapeptide RC-121, is scheduled for clinical trials. To extend previous findings we tested AN-238 on human androgen sensitive MDA-PCa-2b prostate cancers grown subcutaneously and androgen independent LNCaP derived C4-2 prostate cancers xenografted into the tibiae of nude mice. MATERIALS AND METHODS: Changes in serum prostate specific antigen (PSA) levels were monitored by radioimmunoassay. Somatostatin receptors in tumor samples were characterized. RESULTS: Three intravenous injections of AN-238 at 150 nmol/kg doses inhibited the growth of subcutaneous MDA-PCa-2b tumors by 62% vs controls (p <0.05) and were more effective than equimolar doses of the radical AN-201 (p <0.05). AN-238 also decreased serum PSA levels by 62% vs controls (p <0.01). In nude mice bearing intra-osseous implanted C4-2 prostate cancers AN-238 decreased serum PSA levels by 65% compared with controls after 5 weeks of therapy (p <0.05), while AN-201 was ineffective. All AN-238 treated mice were alive at the termination of the experiment, while only 50% of controls and 60% of animals treated with AN-201 survived (p <0.01). Histological evaluation of intraosseous C4-2 tumors showed that AN-238 induced a significant increase in apoptosis (p <0.05). MDA-PCa-2b and C4-2 tumors showed high affinity binding for somatostatin and the expression of mRNA for somatostatin receptor subtypes 1, 2A and 5. CONCLUSIONS: The current study demonstrates the efficacy of the somatostatin analogue AN-238 for subcutaneous MDA-PCa-2b as well as for intraosseous C4-2 prostate cancers xenografted into nude mice. This targeted cytotoxic analogue could represent a new therapy for patients with advanced metastatic prostate carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal Of Urology. - 171 : 2 (2004), p. 911-915. -
További szerzők:Schally, Andrew Victor Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nagy Attila
Internet cím:Szerző által megadott URL
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