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1.

001-es BibID:BIBFORM033615
035-os BibID:PMID:11272290 WOS:000166756100010
Első szerző:Arencibia, José M.
Cím:In vitro targeting of a cytotoxic analog of luteinizing hormone-releasing hormone AN-207 to ES-2 human ovarian cancer cells as demonstrated by microsatellite analyses / Jose M. Arencibia, Andrew V. Schally, Gabor Halmos, Attila Nagy, Hippokratis Kiaris
Dátum:2001
ISSN:0959-4973
Megjegyzések:Targeting of cytotoxic agents represents a modern approach to the treatment of various cancers, that improves the efficacy and reduces peripheral toxicity. Recently we developed a powerful cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), AN-207, designed to be targeted to tumors that express LHRH receptors. This analog consists of the superactive derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201), linked to [D-Lys6]LHRH carrier. In the present study we investigated the cytocidal effects of AN-207 and AN-201 on the LHRH receptor-positive ES-2 ovarian cancer cells. The targeting of AN-207 to ES-2 cells in the presence of LHRH receptor-negative UCI-107 ovarian cancer cells was also evaluated by semi-quantitative polymerase chain reaction (PCR) amplification of microsatellite markers. Ligand competition assays showed a single class of high-affinity and low-capacity binding sites in ES-2 cells with a mean dissociation constant (KD) of 3.93 +/- 0.1 nM and a mean maximal binding capacity (Bmax) of 271 +/- 26.1 fmol/mg membrane protein. Kinetic assays indicated that AN-207 caused cell death in a concentration- and time-dependent manner in ES-2 cells, but not in UCI-107 cells, while the kinetics of cytotoxic effects of AN-201 were similar in both cell lines. To investigate targeting, ES-2 cells were co-cultured with UCI-107 cells, treated with 10 nM AN-207 or AN-201 for different times and then cultured for 48 h in the absence of cytotoxic agents. Genomic DNA was extracted for microsatellite analyses using different markers. Semi-quantitative analyses of the intensity of the alleles that correspond to each cell line indicated that AN-207 was selectively targeted to ES-2 cells, while AN-201 showed no selectivity for either cell line. These results extend our previous findings that AN-207 can be targeted to ovarian cancers and other tumors that express receptors for LHRH. Cytotoxic analogs of LHRH, such as AN-207, should be considered for treatment of LHRH receptor-positive tumors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Anti-Cancer Drugs. - 12 : 1 (2001), p. 71-78. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nagy Attila Kiaris, Hippokratis
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2.

001-es BibID:BIBFORM033656
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers / Gabor Halmos, José M. Arencibia, Andrew V. Schally, Rodney Davis, David G. Bostwick
Dátum:2000
ISSN:0022-5347
Megjegyzések:PURPOSE: Agonistic analogs of luteinizing hormone-releasing hormone (LHRH) are widely used for therapy of advanced prostate cancer based upon their ability to suppress testosterone secretion in patients. Various studies also indicate that LHRH analogs might have direct inhibitory effects on prostate tumors mediated by specific LHRH receptors. In this study we investigated the presence and characteristics of receptors for LHRH and their messenger (m) ribonucleic acid (RNA) expression in specimens of human prostate adenocarcinomas and benign prostatic tissue. MATERIALS AND METHODS: In vitro ligand competition assays as well as reverse transcriptase polymerase chain reaction (RT-PCR) were performed to investigate the expression of receptors for LHRH in surgical specimens of human prostate cancers and benign prostatic tissue. RESULTS: Sixty-nine of 80 (86%) cancers exhibited specific, medium to high-affinity binding for [D-Trp6]LHRH with a dissociation constant (Kd) of 6.55+/-0.4 nM and a maximal binding capacity (Bmax) of 483.6+/-25.4 fmol./mg. membrane protein. Two prostate cancer patients who were treated with the LHRH agonist goserelin prior to prostatectomy did not show tumor LHRH receptors. The expression of mRNA for LHRH receptors was observed in 19 of 22 (86%) prostate cancers. Benign prostatic tissue also displayed LHRH receptor gene expression, but exhibited lower Bmax value. There was a negative correlation (p <0.001) between LHRH receptor binding capacity and cancer grade (Gleason score); higher Gleason scores were associated with significantly lower binding capacity but an increased binding affinity. CONCLUSIONS: The expression of specific receptor proteins for LHRH in human prostate cancer provides a rationale for the improvement in methods for therapy of this malignancy based on LHRH analogs.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal Of Urology. - 163 : 2 (2000), p. 623-629. -
További szerzők:Arencibia, José M. Schally, Andrew Victor Davis, Rodney Bostwick, David G.
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3.

001-es BibID:BIBFORM033660
035-os BibID:PMID:10375109 WOS:000080777900017
Első szerző:Kahán Zsuzsa
Cím:Complete regression of MX-1 human breast carcinoma xenografts after targeted chemotherapy with a cytotoxic analog of luteinizing hormone-releasing hormone, AN-207 / Zsuzsanna Kahán, Attila Nagy, Andrew V. Schally, Gábor Halmos, José M. Arencibia, Kate Groot
Dátum:1999
ISSN:0008-543X
Megjegyzések:BACKGROUND: Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in about 50% of human breast carcinomas. A highly potent cytotoxic agent, 2-pyrrolinodoxorubicin (AN-201), was linked to the agonist [D-Lys6]LH-RH to form a cytotoxic LH-RH analog, AN-207, that can be targeted to LH-RH receptors on breast carcinomas. METHODS: Nude mice bearing MX-1 hormone-independent, doxorubicin-resistant human breast carcinomas were injected intravenously with vehicle (control), 250 nmol/kg doses of AN-201, AN-207, or an unconjugated mixture of AN-201 and [D-Lys6]LH-RH. Tumor growth and changes in hematologic parameters were evaluated. Receptors for LH-RH were investigated by radioreceptor assays, and the expression of their mRNA was determined by reverse transcriptase-polymerase chain reaction. RESULTS: AN-207 caused complete regression of MX-1 tumors in all 10 animals, and they were still tumor free 60 days after treatment. In contrast, after therapy with AN-201 or the mixture of AN-201 and [D-Lys6]LH-RH, the regression of most MX-1 tumors was only transitory. AN-201 caused the death of 1 of the 10 animals and significantly greater leukopenia than AN-207, which produced no toxic deaths. Radioreceptor assays revealed high affinity binding sites for LH-RH on tumor cell membranes. The expression of mRNA for LH-RH receptors also was found in tumors. CONCLUSIONS: The results of this study indicate that powerful, targeted cytotoxic LH-RH analogs such as AN-207 could be considered for the treatment of human breast carcinomas that possesses receptors for LH-RH.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer. - 85 : 12 (1999), p. 2608-2615. -
További szerzők:Nagy Attila Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Arencibia, José M. Groot, Kate
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4.

001-es BibID:BIBFORM033641
Első szerző:Kahán Zsuzsa
Cím:Administration of a targeted cytotoxic analog of luteinizing hormone-releasing hormone inhibits growth of estrogen-independent MDA-MB-231 human breast cancers in nude mice / Zsuzsanna Kahán, Attila Nagy, Andrew V. Schally, Gábor Halmos, José M. Arencibia, Kate Groot
Dátum:2000
ISSN:0167-6806
Megjegyzések:Receptor targeted chemotherapy is less toxic and more effective than conventional chemotherapy. Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in about 50% of human breast cancers. Highly potent cytotoxic radical 2-pyrrolinodoxorubicin (AN-201) was linked to the agonistic analog [D-Lys6]LH-RH to form cytotoxic LH-RH analog AN-207. We evaluated whether AN-207 could be targeted to the hormone-independent MDA-MB-231 human breast cancers. Nude mice bearing MDA-MB-231 tumors were injected i.v. with 250 nmol/kg doses of cytotoxic radical AN-201, cytotoxic LH-RH analog AN-207, the unconjugated mixture of AN-201 and carrier [D-Lys6]LH-RH, [D-Lys6]LH-RH alone and vehicle (control). The growth of MDA-MB-231 tumors in animals given a single dose of AN-207 was inhibited significantly (p = 0.01) for 3 weeks after injection, whereas tumors in all the other groups grew steadily. All cytotoxic compounds produced leukopenia, but the strongest lymphocyte suppression was caused by cytotoxic radical AN-201. Three weeks after treatment, the presence of mRNA for LH-RH receptors was demonstrated by RT-PCR in all the groups and radioreceptor assays demonstrated high-affinity binding sites for LH-RH on tumor cell membranes of control animals and those treated with AN-201, the carrier peptide alone or in combination with AN-201. At this time point binding assays did not reveal the expression of membrane proteins in tumors treated with AN-207, but 60 days after administration of AN-207, high affinity LH-RH binding sites were found again in MDA-MB-231 tumors. These results indicate that cytotoxic LH-RH analog AN-207 could be utilized for receptor targeted chemotherapy of breast cancers expressing receptors for LH-RH.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Breast Cancer Research and Treatment. - 59 : 3 (2000), p. 255-262. -
További szerzők:Nagy Attila Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Arencibia, José M. Groot, Kate
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5.

001-es BibID:BIBFORM033650
Első szerző:Kahán Zsuzsa
Cím:Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II / Zsuzsanna Kahán, Baodong Sun, Andrew V. Schally, José M. Arencibia, Ren-Zhi Cai, Kate Groot, Gábor Halmos
Dátum:2000
ISSN:0008-543X
Megjegyzések:BACKGROUND: The growth of breast carcinoma is promoted by autocrine growth factors such as the bombesin (BN)-like peptides and epidermal growth factor (EGF). The stimulatory action of BN-like peptides can be blocked by the use of BN/gastrin-releasing peptide (GRP) antagonists. METHODS: The authors investigated the effects of synthetic BN/GRP antagonists RC-3095 and RC-3940-II on tumor growth and the expression of mRNA for EGF receptors and three BN receptor subtypes in MDA-MB-468 human breast carcinoma. Athymic nude mice with xenografts of MDA-MB-468 human breast carcinoma were injected subcutaneously for 6 weeks with RC-3940-II at doses of 20 or 40 microg/day. In another study, the effects of RC-3940-II and RC-3095 were compared. RESULTS: RC-3940-II caused a significant and dose-dependent growth inhibition of MDA-MB-468 tumors in nude mice; therapy with either dose of RC-3940-II significantly (P<0.01) reduced the mean final tumor volume and weight compared with controls. RC-3940-II induced a persistent regression of > 50% of all tumors. One of 3 tumors treated with 20 microg of RC-3940-II and 3 of 5 tumors treated with 40 microg were found to have regressed completely by the end of the study. When RC-3940-II and RC-3095 were compared at the dose of 20 microg/day, both powerfully suppressed growth of MDA-MB-468 tumors, with RC-3940-II causing a complete regression of 2 tumors and RC-3095 a complete regression of 1 tumor. Receptor analyses of untreated MDA-MB-468 tumors revealed an overexpression of EGF receptors and two classes of binding sites for BN/GRP. mRNAs for receptors of GRP, neuromedin B, and BN receptor subtype-3 were detected by reverse transcriptase-polymerase chain reaction. CONCLUSIONS: A virtual arrest of growth or regression of MDA-MB-468 human breast carcinoma after therapy with RC-3940-II and RC-3095 indicates that these BN/GRP antagonists could provide a new treatment modality for breast tumors expressing BN and EGF receptors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer. - 88 : 6 (2000), p. 1384-1392. -
További szerzők:Sun, Baodong Schally, Andrew Victor Arencibia, José M. Cai, Ren-Zhi Groot, Kate Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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6.

001-es BibID:BIBFORM036995
Első szerző:Koppán Miklós
Cím:Targeted Cytotoxic Analog of Luteinizing Hormone-Releasing Hormone AN-207 Inhibits the Growth of PC-82 Human Prostate Cancer in Nude Mice / Koppán Miklós, Nagy Attila, Andrew V. Schally, Arthur Plonowski, Halmos Gábor, José M. Arencibia, Kate Groot
Dátum:1999
ISSN:0270-4137
Megjegyzések:BACKGROUND: Receptors for luteinizing hormone-releasing hormone (LH-RH) found in prostate cancers might be used for targeting of chemotherapeutic agents. Doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to carrier analog [D-Lys6]LH-RH to form the targeted cytotoxic analog of LH-RH, AN-207. METHODS: We evaluated the effects of AN-207 and its components on the growth of LH-RH receptor-positive human prostate cancer PC-82 xenografted into nude mice. Analog AN-207, radical AN-201, carrier [D-Lys6]LH-RH, or a mixture of [D-Lys6]LH-RH and AN-201 were injected intravenously once at doses of 200 nmol/kg. Tumor growth, body weight, total WBC counts, and serum prostate-specific antigen (PSA) were determined. Receptors for LH-RH on PC-82 tumors were evaluated, and the expression of mRNA for LH-RH receptors was assessed by RT-PCR. RESULTS: Eight weeks after administration of cytotoxic analog AN-207, there was a 67.8% reduction in tumor volume (P < 0.01), 70.7% decrease in tumor burden (P < 0.01), and 36.5% decrease in serum PSA levels (P < 0.01) as compared with controls. Only one of 8 animals treated with AN-207 died. Cytotoxic radical AN-201 caused a 34.2% (not significant, NS) reduction in tumor volume with no change in serum PSA, and killed 3 of 8 mice due to toxicity. Carrier [D-Lys6]LH-RH and the unconjugated mixture of [D-Lys6]LH-RH and AN-201 had no effect on tumor growth. LH-RH receptors as well as the expression of their mRNA were found in PC-82 tumors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
prostate cancer
PC-82 tumor
LH-RH receptor
targeted chemotherapy
2-pyrrolinodoxorubicin
Megjelenés:The Prostate. - 38 : 2 (1999), p. 151-158. -
További szerzők:Nagy Attila Schally, Andrew Victor Plonowski, Artur Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Arencibia, José M. Groot, Kate
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

7.

001-es BibID:BIBFORM033683
035-os BibID:PMID:9762934 WOS:000076070200010
Első szerző:Koppán Miklós
Cím:Bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II inhibit tumor growth and decrease the levels and mRNA expression of epidermal growth factor receptors in H-69 small cell lung carcinoma / Miklós Koppán, Gábor Halmos, José M. Arencibia, Najib Lamharzi, Andrew V. Schally
Dátum:1998
ISSN:0008-543X
Megjegyzések:BACKGROUND: Antagonists of bombesin/gastrin-releasing peptide (BN/GRP) have been developed to block the autocrine stimulatory effect of BN/GRP on tumors such as small cell lung carcinoma (SCLC). Although several studies have addressed the intracellular events that follow the formation of the receptor-ligand complex, the mechanism of action of BN/GRP antagonists remains unclear. METHODS: In this study the authors investigated the effect of synthetic BN/GRP antagonists RC-3095 and RC-3940-II on tumor growth and the expression of epidermal growth factor receptors (EGF-R) in H-69 SCLC. Athymic nude mice xenografted with H-69 SCLC were treated subcutaneously for 5 weeks with RC-3095 and RC-3940-II at the dose of 10 microg/animal/day. RESULTS: RC-3095 decreased tumor volume by approximately 50% (P < 0.05) and RC-3940-II by 70-60% (P < 0.01). Tumor burden also was significantly decreased in the groups treated with RC-3095 and RC-3940-II. Receptor analyses demonstrated high affinity binding sites for BN/GRP and EGF on the untreated H-69 SCLC tumors. After treatment with RC-3095 and RC-3940-II, the concentration of receptors for BN/GRP was decreased by 29.0% and 36.5%, respectively (both, P < 0.01) compared with controls, and EGF-R levels were reduced by 62.3% and 63.0%, respectively (both, P < 0.01). Reverse transcriptase-polymerase chain reaction and Southern blot analyses revealed that the levels of mRNA for EGF-R in tumors were lowered by 31% (P < 0.05) and 43% (P < 0.01), respectively, after treatment with RC-3095 and RC-3940-II. CONCLUSIONS: This study indicates that the inhibition of growth of H-69 SCLC by BN/GRP antagonists RC-3095 and RC-3940-II is accompanied by a marked decrease in the levels and mRNA expression of EGF-R.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer. - 83 : 7 (1998), p. 1335-1343. -
További szerzők:Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Arencibia, José M. Lamharzi, Najib Schally, Andrew Victor
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Borító:

8.

001-es BibID:BIBFORM033666
035-os BibID:PMID:9751625 WOS:000075987800024
Első szerző:Koppán Miklós
Cím:Targeted cytotoxic analogue of somatostatin AN-238 inhibits growth of androgen-independent Dunning R-3327-AT-1 prostate cancer in rats at nontoxic doses / Miklos Koppan, Attila Nagy, Andrew V. Schally, Jose M. Arencibia, Artur Plonowski, Gabor Halmos
Dátum:1998
Megjegyzések:Receptors for somatostatin (SST) that are found on prostate cancers might be used for targeting of chemotherapeutic agents. Thus, doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to SST analogue RC-121 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2) to form targeted cytotoxic SST analogue AN-238. In this study, we evaluated the effects of AN-238 on the growth of SST receptor (SSTR)-positive androgen-independent Dunning R-3327-AT-1 prostate cancers in Copenhagen rats. The dose range and tumor growth-inhibitory effects of AN-238 and AN-201 were investigated in preliminary experiments. Administration of cytotoxic radical AN-201 at single i.v. doses of 110, 125, and 150 nmol/kg resulted in 0, 77.7, and 100% mortality, respectively, within 6-10 days. Four weeks after the injection of 110 nmol/kg AN-201, mean tumor volume was reduced by 35.1 % (P < 0.05), as compared with controls. In contrast, a single i.v. injection of analogue AN-238 at a dose of 300 nmol/kg was nontoxic and remarkably potent in inhibiting the growth of Dunning AT-1 tumors, resulting in a 85.9% (P < 0.01) reduction in tumor volume after 4 weeks. Treatment with AN-238 extended the survival time of tumor-bearing rats from 52.0+/-3.75 to 91.8+/-3.70 days, corresponding to a 76.5% (P < 0.01) increase. In a comprehensive experiment, we compared the effects of radical AN-201 at 115 nmol/kg, analogue AN-238 at 115 and 300 nmol/kg, carrier SST analogue RC-121 at 300 nmol/kg, and a mixture of AN-201 and RC-121 at doses of 300 nmol/kg administered i.v. Administration of AN-201 at 115 nmol/kg led to 90.0% mortality in 12 days, but animals treated with 115 nmol/kg of AN-238 showed no signs of toxicity, their tumor volume was reduced by 40.0% (P < 0.05), and their tumor weight was reduced by 42.8% (P < 0.01) after 4 weeks, as compared with controls. The dose of 300 nmol/kg of AN-238 was also nontoxic and diminished tumor volume by 80.9% (P < 0.01) and tumor weight by 82.0% (P < 0.01). No reduction in tumor growth or toxic effects was observed with carrier RC-121, but after the injection of unconjugated mixture of AN-201 and RC-121 at doses of 300 nmol/kg, all rats died within 4 days. Specific high-affinity receptors for SST were found on Dunning R-3327-AT-1 tumor membranes by radioligand binding assay and were identified by reverse transcription-PCR as SSTR2. Our study indicates that cytotoxic SST analogue AN-238 can be targeted to SSTRs on tumors and produces a powerful inhibition of the growth of Dunning-AT-1 rat prostate cancer at doses that are nontoxic, whereas its cytotoxic component, 2-pyrrolinodoxorubicin, is toxic and ineffective.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer Research. - 58 : 18 (1998), p. 4132-4137. -
További szerzők:Nagy Attila Schally, Andrew Victor Arencibia, José M. Plonowski, Artur Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM033612
035-os BibID:PMID:11571730 WOS:000170972000015
Első szerző:Plonowski, Artur
Cím:Inhibition of the UCI-107 human ovarian carcinoma cell line by a targeted cytotoxic analog of somatostatin, AN-238 / Artur Plonowski, Andrew V. Schally, Miklos Koppan, Attila Nagy, Jose M. Arencibia, Balazs Csernus, Gabor Halmos
Dátum:2001
ISSN:0008-543X
Megjegyzések:BACKGROUND: Cytotoxic analogs of somatostatin (SST), such as AN-238, which consists of 2-pyrrolinodoxorubicin (AN-201) linked to the SST carrier RC-121, can be targeted to tumors that express SST receptors. Because SST receptors are present in ovarian carcinoma cells, the authors evaluated the effect of AN-238 on the UCI-107 ovarian carcinoma cell line. METHODS: An analysis of microsatellite alleles in cocultured SST receptor positive and receptor negative cells was used for the demonstration of in vitro targeting. The toxicity and antitumor effects of AN-238 in nude mice bearing UCI-107 human ovarian tumors were investigated with or without pharmacologic inhibition of serum carboxylesterases (CE). The expression of SST receptor subtypes was determined by reverse transcriptase-polymerase chain reaction analysis, and the binding affinity of AN-238 to SST receptors was determined by radioligand assays. RESULTS: The proliferation of SST receptor positive UCI-107 cells in vitro was inhibited preferentially by AN-238. AN-238 showed high-affinity binding to UCI-107 tumor membranes at a 50% inhibition concentration of 3.39 nM +/- 0.74 nM. In vivo, the volume and weights of UCI-107 tumors treated with AN-238 were decreased by more than 60% (P < 0.05) compared with controls. Cytotoxic radical AN-201 or the unconjugated mixture of AN-201 with carrier RC-121 had no significant effects on tumors and were toxic. In mice with inhibited serum CE activity, AN-201 at 400 nmol/kg was lethal, whereas AN-238 at a total dose of 800 nmol/kg caused only 22% mortality and reduced tumor weight by 69% and volume by 70% (P < 0.05 vs. control). CONCLUSIONS: Targeted chemotherapy with the SST conjugate AN-238 inhibits SST receptor positive experimental ovarian tumors. AN-238 may provide a new treatment modality for patients with advanced ovarian carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer. - 92 : 5 (2001), p. 1168-1176. -
További szerzők:Schally, Andrew Victor Koppán Miklós Nagy Attila Arencibia, José M. Csernus Balázs Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM033663
035-os BibID:PMID:10480336 WOS:000082305800002
Első szerző:Szepesházi Károly
Cím:Growth inhibition of experimental pancreatic cancers and sustained reduction in epidermal growth factor receptors during therapy with hormonal peptide analogs / Karoly Szepesházi, Gabor Halmos, Andrew V. Schally, José M. Arencibia, Kate Groot, Manuel Vadillo-Buenfil, Eulalia Rodriguez-Martin
Dátum:1999
ISSN:0171-5216
Megjegyzések:Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers were treated for 8 weeks with bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems releasing 20, 35 and 20 microg analog/ day respectively. To establish the pattern of changes in the number and affinity of EGF receptors on tumors, groups of animals were sacrificed at regular intervals during therapy. Chronic treatment with RC-3095 or Cetrorelix resulted in an early (day 10) and sustained reduction (71% or 69% respectively) in EGF receptors on pancreatic tumors. In contrast, RC-160 decreased receptor concentration by 60% only after 20 days. Among the histological characteristics of proliferation, the decrease in argyrophilic nucleolar organizer regions, but not apoptotic and mitotic indices, showed a correlation with the fall in EGF receptors. The concentration of the receptors returned to the control level 4 days after cessation of chronic treatment with RC-3095. The effect of single injections of RC-3095, RC-160 and Cetrorelix on EGF receptors was also investigated. RC-160 decreased the number of EGF receptors on pancreatic cancers by 31% 3 h after administration, but the receptors had returned to normal level at 6 h. RC-3095 and Cetrorelix caused a 67% and 59% decline, respectively, in EGF receptors only 6 h after injection and the concentration of receptors remained low for 24 h. Thus, the pattern of downregulation of EGF receptors in pancreatic cancers appears to depend on the peptide used for therapy. Since the antitumor effect may be the result of the fall in EGF receptors in cancers, information on the time course of changes in these receptors during treatment with these analogs may lead to an improvement in therapeutic regimens.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal of Cancer Research and Clinical Oncology. - 125 : 8-9 (1999), p. 444-452. -
További szerzők:Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Schally, Andrew Victor Arencibia, José M. Groot, Kate Vadillo-Buenfil, Manuel Rodriguez-Martin, Eulalia
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