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001-es BibID:BIBFORM033598
035-os BibID:WOS:000185548300031
Első szerző:Bajo, Ana-Maria
Cím:Targeted doxorubicin-containing luteinizing hormone-releasing hormone analogue AN-152 inhibits the growth of doxorubicin-resistant MX-1 human breast cancers / Ana M. Bajo, Andrew V. Schally, Gabor Halmos, Attila Nagy
Dátum:2003
Megjegyzések:Purpose: The receptors for luteinizing hormone-releasing hormone receptor (LHRH-R) are found in >50% of human breast cancers. Doxorubicin (DOX) was linked to [D-Lys(6)]LHRH to form a cytotoxic conjugate, AN-152, which can be targeted to tumor cells expressing LHRH-R. We evaluated the effects of AN-152 on the estrogen-independent, DOX-resistant human mammary carcinoma line MX-1, xenografted into nude mice. Experimental Design: Nude mice bearing MX-1 tumors were administered five i.v. injections of AN-152 or DOX at doses equivalent to 3 mg/kg DOX. Tumor growth was followed, and changes in the expression of LHRH-R on tumors were evaluated by radioreceptor assays, reverse transcription-PCR, and Western blotting. The effects of AN-152 on the expression of human epidermal growth factor receptor (HER)-2 were investigated. Because LHRH-R are coupled to various G proteins, which are involved in mitogenic signaling, we determined the outcome of treatment with AN-152 on the levels of mRNA for different G proteins. Results: Treatment with AN-152 significantly (P < 0.05) decreased the final tumor volume to 978.56 +/- 176.85 mm(3), compared with the control tumors, which measured 2837.38 +/- 515.38 mm(3). Tumor doubling time was likewise significantly (P < 0.05) extended by AN-152 to 12.01 +/- 1.99 days from 6.45 +/- 0.36 days for the controls. Therapy with AN-152, but not with DOX, resulted in a significant decrease of LHRH-R levels on MX-1 tumors. The expression of mRNAs for HER-2, HER-3, Galpha(i2), and Galpha(11) and the levels of HER-2 and HER-3 proteins were also significantly reduced by AN-152. Conclusions: Cytotoxic LHRH analogue AN-152 could be considered for targeted chemotherapy of DOX-resistant breast cancers expressing LHRH-R.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Clinical Cancer Research. - 9 : 10 (2003), p. 3742-3748. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nagy Attila
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM033596
035-os BibID:PMID:14508826 WOS:000185464100010
Első szerző:Szepesházi Károly
Cím:Preclinical evaluation of therapeutic effects of targeted cytotoxic analogs of somatostatin and bombesin on human gastric carcinomas / Karoly Szepeshazi, Andrew V. Schally, Attila Nagy, Brady W. Wagner, Ana Maria Bajo, Gabor Halmos
Dátum:2003
ISSN:0008-543X
Megjegyzések:BACKGROUND: New modalities are necessary for the treatment of patients with unresectable gastric carcinoma. The authors investigated whether receptors for somatostatin and bombesin were present in human gastric carcinoma lines and tested the antitumor effects of cytotoxic somatostatin analog AN-238 and cytotoxic bombesin conjugate AN-215. METHODS: Nude mice bearing AGS, Hs 746T, and NCI-N87 human gastric carcinomas were treated with AN-238, AN-215, or their cytotoxic moiety 2-pyrrolinodoxorubicin (AN-201). Tumor growth reduction and tumor doubling times were calculated, and histologic characteristics of cell proliferation and apoptosis were examined. The expression of mRNA for somatostatin and bombesin receptors in tumors was investigated by reverse transcriptase-polymerase chain reaction. Subtypes 2 and 5 of somatostatin receptor proteins (sst2 and sst5, respectively) were analyzed using immunohistochemistry and immunoblotting. Binding assays were performed with radiolabeled somatostatin and bombesin analogs. RESULTS: Cytotoxic bombesin analog AN-215 powerfully inhibited the growth of AGS carcinomas that expressed high-affinity subtype 1 bombesin receptors. All three carcinomas expressed high-affinity sst2 and sst5 receptors. Cytotoxic somatostatin analog AN-238 exerted a strong inhibitory effect on NCI-N87 and Hs 746T carcinomas, which exhibited high concentrations of somatostatin receptors, but had a weaker effect on AGS tumors, which expressed the lowest receptor levels. AN-201 had only nonsignificant effects. CONCLUSIONS: Experimental human gastric carcinomas that expressed high-affinity subtype 1 bombesin receptors were inhibited by cytotoxic bombesin analog AN-215, and tumors with high concentrations of sst2 or sst5 somatostatin receptors were suppressed by cytotoxic somatostatin analog AN-238. These findings suggest that this class of targeted compounds should be considered for the therapy of patients with advanced gastric carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Cancer. - 98 : 7 (2003), p. 1401-1410. -
További szerzők:Schally, Andrew Victor Nagy Attila Wagner, Brady W. Bajo, Ana-Maria Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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3.

001-es BibID:BIBFORM033601
035-os BibID:WOS:000175800700021 PMID:11953892
Első szerző:Szereday Zoltán
Cím:Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215 / Z. Szereday, A. V. Schally, A. Nagy, A. Plonowski, A. M. Bajo, G. Halmos, K. Szepeshazi, K. Groot
Dátum:2002
Megjegyzések:Some brain tumours, such as glioblastomas express high levels of receptors for bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carner. This study reports the effect of AN-215 on the growth of U-87MG human glioblastomas xenografted into nude mice. High affinity binding of AN-2115 to U-87MG tumours was charactensed by an IC50 value of 4.0+/-0.1 nM, as determined by radioreceptor assays. mRNA analyses revealed the presence of mRNA for BN receptor subtypes 1 and 2. Treatment with AN-215 significantly (P<0.05) extended tumour doubling time from 4.54+/-0.2 days to 8.18 +/- 1.8 day sand inhibited tumour growth as demonstrated by a 69.6% reduction in final tumour volume (P<0.001) and a 64.6% decrease in tumour weight as compared to controls. Cytotoxic radical AN-201 at the same dose was ineffective. The anti-tumour effect of AN-215 could be blocked by pretreatment with an excess of a bombesin antagonist, indicating that the action of this cytotoxic analogue is receptor-mediated. Our results suggest that patients with inoperable brain tumours such as malignant gliomas may benefit from targeted chemotherapy based on cytotoxic bombesin analogue AN-215.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:British journal of cancer. - 86 : 8 (2002), p. 1322-1327. -
További szerzők:Schally, Andrew Victor Nagy Attila Plonowski, Artur Bajo, Ana-Maria Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Groot, Kate
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM033716
Első szerző:Szereday Zoltán
Cím:Effective treatment of H838 human non-small cell lung carcinoma with a targeted cytotoxic somatostatin analog, AN-238 / Zoltan Szereday, Andrew V. Schally, Karoly Szepeshazi, Ana-Maria Bajo, Francine Hebert, Gabor Halmos, Attila Nagy
Dátum:2003
Megjegyzések:The accumulation of radioactive somatostatin analog [111In]pentetreotide in non-small cell lung cancer (non-SCLC) during scintigraphy of patients provides a rationale for investigating the efficacy of somatostatin receptor-based chemotherapy in non-SCLC. Consequently, in this study, we evaluated the antitumor effects of cytotoxic somatostatin analog AN-238 on H838 human non-SCLC xenografted into nude mice in comparison with its cytotoxic radical, 2-pyrrolinodoxorubicin (AN-201). The expression of messenger RNA (mRNA) for human somatostatin receptor subtypes 2 (hsst2) and 5 (hsst5) in H838 cells, and tumors was also investigated using reverse-transcription polymerase chain reaction (RT-PCR). Somatostatin receptors on H838 tumors were characterized by ligand competition assay using radiolabeled somatostatin analog, RC-160. Three i.v. injections of AN-238 at 150 nmol/kg, given on days 1, 7 and 21, resulted in a significant (p<0.05) tumor growth inhibition, the final tumor volume being 60% smaller than in the controls. The tumor doubling time was also extended significantly (p<0.05) from 9.65+/-0.56 days in the controls to 17.52+/-3.3 days. Only one of 8 mice died due to toxicity. In contrast, cytotoxic radical AN-201 was ineffective and more toxic, killing 2 of 7 animals. mRNA for hsst2 was found in H838 xenografts, but not in H838 cells from which the xenografts originated. Interestingly, H838 cells grown in a special, serum-free medium did express mRNA for hsst2. mRNA for hsst5 was not found in any samples tested. Binding studies demonstrated the presence of high affinity (K(d) = 7.3+/-1.2 nM) binding sites for RC-160 with a mean maximal binding capacity (B(max)) of 953.3+/-45.3 fmol/mg protein. AN-238 at 3.14+/-0.93 nM concentration displaced 50% of radiolabeled RC-160 binding to somatostatin receptors in H838 tumors. Our results indicate that patients with inoperable non-SCLC may benefit from chemotherapy targeted to somatostatin receptors based on AN-238.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:International Journal of Oncology. - 22 : 5 (2003), p. 1141-1146. -
További szerzők:Schally, Andrew Victor Szepesházi Károly Bajo, Ana-Maria Hebert, Francine Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nagy Attila
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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