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1.

001-es BibID:BIBFORM033649
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:High expression of somatostatin receptors and messenger ribonucleic acid for its receptor subtypes in organ-confined and locally advanced human prostate cancers / Gabor Halmos, Andrew V. Schally, Baodong Sun, Rodney Davis, David G. Bostwick, Artur Plonowski
Dátum:2000
ISSN:0021-972X
Megjegyzések:To evaluate the potential application of somatostatin (SST) analogs as an adjuvant treatment for prostate cancer, we characterized the binding sites for SST octapeptide analogs on prostate cancers in patients treated with radical prostatectomy. The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class of specific binding sites for RC-160 with a mean dissociation constant (K(d)) of 9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason score of 8-10), the incidence of RC-160 binding (65.7%) was similar to that observed in the low risk group (64.3%). The demonstration of the high incidence of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate cancers supports the merit of further investigations of the application of SST analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment of patients at high risk of cancer recurrence after radical prostatectomy. Such approaches could be also considered for patients with advanced prostate cancer at the time of relapse.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:The Journal of Clinical Endocrinology and Metabolism. - 85 : 7 (2000), p. 2564-2571. -
További szerzők:Schally, Andrew Victor Sun, Baodong Davis, Rodney Bostwick, David G. Plonowski, Artur
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2.

001-es BibID:BIBFORM033620
035-os BibID:WOS:000089341400049
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Human renal cell carcinoma expresses distinct binding sites for growth hormone-releasing hormone / Gabor Halmos, Andrew V. Schally, Jozsef L. Varga, Artur Plonowski, Zoltan Rekasi, Tamas Czompoly
Dátum:2000
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) inhibit the proliferation of various human cancers in vitro and in vivo by mechanisms that include apparent direct effects through specific binding sites expressed on tumors and that differ from pituitary human GHRH (hGHRH) receptors. In this study, GHRH antagonist JV-1-38 (20 mu g/day per animal s.c,) inhibited the growth of orthotopic CAKI-1 human renal cell carcinoma (RCC) by 83% and inhibited the development of metastases to lung and lymph nodes. Using ligand competition assays with I-125-labeled GHRH antagonist JV-1-42. we demonstrated the presence of specific high-affinity (K-d = 0.25 +/- 0.03 nM) binding sites for GHRH with a maximal binding capacity (B-max) Of 70.2 +/- 4.1 fmol/mg of membrane protein in CAKI-1 tumors. These receptors bind GHRH antagonists preferentially and display a lower affinity for hGHRH. The binding of I-125-JV-1-42 is not inhibited by vasoactive intestinal peptide (VIP)-related peptides sharing structural homology with hGHRH. The receptors for GHRH antagonists on CAKI-1 tumors are distinct from binding sites detected with I-125-VIP (K-d = 0.89 +/- 0.14 nM; B-max = 183.5 +/- 2.6 fmol/mg of protein) and also have different characteristics from GHRH receptors on rat pituitary as documented by the insignificant binding of [His(1),I-125-Tyr(10),Nle(27)]hGHRH(1-32)NH2. Reverse transcription-PCR revealed the expression of splice variants of hGHRH receptor in CAKI-1 RCC. Biodistribution studies demonstrate an in vivo uptake of I-125-JV-1-42 by the RCC tumor tissue. The presence of specific receptor proteins that bind GHRH antagonists in CAKI-1 RCC supports the view that distinct binding sites that mediate the inhibitory effect of GHRH antagonists are present on various 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. - 97 : 19 (2000), p. 10555-10560. -
További szerzők:Schally, Andrew Victor Varga József L. Plonowski, Artur Rékási Zoltán Czompoly Tamás
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3.

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
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4.

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)
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5.

001-es BibID:BIBFORM033637
Első szerző:Plonowski, Artur
Cím:Inhibition of metastatic renal cell carcinomas expressing somatostatin receptors by a targeted cytotoxic analogue of somatostatin AN-238 / Artur Plonowski, Andrew V. Schally, Attila Nagy, Hippokratis Kiaris, Francine Hebert, Gabor Halmos
Dátum:2000
Megjegyzések:The effectiveness of chemotherapy targeted to somatostatin (SST) receptors based on cytotoxic SST analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to SST carrier octapeptide, was investigated in human renal cell carcinomas (RCCs). SST receptors, which showed high-affinity binding for AN-238, were found in the SW-839 RCC line with sst2A subtype and in the 786-0 RCC line, which expressed the sst5 subtype. CAKI-1 RCC, which does not express sst2A or sst5, was used as a negative control for testing the specificity of SST receptor targeting. Using microsatellite analysis, AN-238 was shown to selectively inhibit the proliferation of 786-0 line, but not the CAKI-1 RCC line in vitro. The effects of three i.v. injections of 150 nmol/kg of AN-238 or AN-201, given on days 1, 8, and 21, were evaluated in groups of nude mice bearing s.c. xenografts of SW-839 and 786-0 RCC. After 5 weeks, the volumes of SW-839 and 786-0 RCC tumors were decreased by 67.2 (P < 0.05) and 78.3% (P < 0.01), respectively, whereas AN-201 had no significant effect on tumor growth. The inhibition of SST receptor-negative CAKI-1 tumors by AN-238 was only marginal. To investigate the efficacy of SST receptor-targeted chemotherapy in metastatic RCC, three i.v. injections of AN-238 or AN-201 at 150 nmol/kg were given at biweekly intervals to nude mice implanted with 786-0 tumors under the renal capsule. After 6 weeks, the weight of orthotopic tumors treated with AN-238 (55.3 +/- 44.3 mg) was significantly lower (87% reduction; P < 0.001) than that in the control group (414.2 +/- 41.0 mg) or in animals given AN-201 (270.2 +/- 603 mg; P < 0.05). Five of six animals (83%), both in the control and the AN-201 group, developed metastases to lymph nodes, but only one of seven mice (14%) given AN-238 showed lymphatic spread. Lung metastases were found in 83% of controls and 50% of AN-201 treated animals, but none occurred in mice treated with AN-238. This study demonstrates that targeted cytotoxic SST analogue AN-238 provides an effective therapy for chemoresistant neoplasms such as RCC. Because most clinical RCCs express SST receptors, this treatment modality might be beneficial to patients with metastatic disease.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer Research. - 60 : 11 (2000), p. 2996-3001. -
További szerzők:Schally, Andrew Victor Nagy Attila Kiaris, Hippokratis Hebert, Francine Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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6.

001-es BibID:BIBFORM033639
Első szerző:Plonowski, Artur
Cím:Potentiation of the inhibitory effect of growth hormone-releasing hormone antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of interference with both IGF and EGF pathways / Artur Plonowski, Andrew V. Schally, Jozsef L. Varga, Zoltan Rekasi, Francine Hebert, Gabor Halmos, Kate Groot
Dátum:2000
ISSN:0270-4137
Megjegyzések:BACKGROUND: In view of the involvement of various neuropeptides and growth factors in the progression of androgen-independent prostate cancer, we investigated the effects of antagonists of growth hormone-releasing hormone (GHRH) alone or in combination with an antagonist of bombesin/gastrin-releasing peptide (BN/GRP) on PC-3 human prostate cancers. METHODS: Nude mice implanted with PC-3 tumors received GHRH antagonists MZ-5-156 or JV-1-38, each at 20 microgram/day s.c. In experiment 2, treatment consisted of daily injections of JV-1-38 (20 microgram), BN/GRP antagonist RC-3940-II (10 microgram), or a combination of JV-1-38 and RC-3940-II. Serum IGF-I levels, expression of mRNA for IGF-II, and characteristics of BN/GRP and EGF receptors in tumor tissue were investigated. RESULTS: JV-1-38 induced a greater inhibition of tumor growth and suppression of IGF-II mRNA than MZ-5-156, both compounds causing a similar decrease in serum IGF-I. In experiment 2, JV-1-38 and RC-3940-II produced a comparable reduction in tumor volume (65% and 61%, respectively), but a combination of both antagonists augmented tumor inhibition to 75%. Combined treatment with JV-1-38 and RC-3940-II also led to a greater suppression of IGF-II mRNA (92%), as compared with JV-1-38 (72%) or RC-3940-II (77%). Serum IGF-I concentration was lowered only in mice treated with JV-1-38, while the downregulation of BN/GRP and EGF receptors was specific for groups receiving RC-3940-II. CONCLUSIONS: The inhibitory effects of GHRH antagonists on PC-3 human androgen-independent prostate cancer can be potentiated by concomitant use of BN/GRP antagonists. The combination of both types of analogs apparently interferes with both IGF and bombesin/EGF pathways, and might be clinically useful for the management of androgen-independent prostate cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Prostate. - 44 : 2 (2000), p. 172-180. -
További szerzők:Schally, Andrew Victor Varga József L. Rékási Zoltán Hebert, Francine Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate
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7.

001-es BibID:BIBFORM033634
035-os BibID:WOS:000090134500021 PMID:11058885
Első szerző:Plonowski, Artur
Cím:In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215 / Artur Plonowski, Attila Nagy, Andrew V. Schally, Baodong Sun, Kate Groot, Gabor Halmos
Dátum:2000
ISSN:0020-7136
Megjegyzések:The effectiveness of chemotherapy targeted to bombesin (BN) receptors was evaluated in nude mice bearing PC-3 human androgen-independent prostate cancers. Cytotoxic BN analogue AN-215, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to BN-like carrier peptide RC-3094, was injected i.v. at 150 nmol/kg on days I, II and 21, After treatment with AN-215, tumor volume was 69% (p < 0.01) smaller than that in controls and tumor doubling time was extended from 8.5 +/- 0.7 days to 20.3 +/- 3.5 days (p < 0.05). Cytotoxic radical AN-201, carrier RC-3094 and their unconjugated mixture administered at the same dosage were ineffective. The mortality rate was 12.5% in the AN-201 group and 16.7% in the group treated with the mixture, but no deaths occurred in mice receiving AN-215, Because the ester bond linking AN-201 to the carrier molecule is hydrolyzed much faster in mouse serum than in human serum, in the second experiment we investigated the tolerance to AN-215 and its effect in nude mice bearing PC-3 tumors after pharmacological inhibition of serum carboxylesterases, Two applications of AN-201 at 200 nmol/kg were lethal, whereas no mortality was observed after 4 injections of AN-215 at the same dose. Administration of 200 nmol/kg AN-215 on days I, 7, 17 and 26 again produced 69% tumor inhibition. BN receptors on membranes of PC-3 tumors were detected by I-125-[Tyr(4)]BN binding, and expression of mRNA for BRS-3 and GRP-R subtypes was also found, AN-215 showed a high affinity to PC-3 tumors, displacing the radioligand at an IC50 of 12.95 +/- 0.35 nM, Because BN receptors are present on primary and metastatic prostate cancer, targeted chemotherapy with AN-215 might benefit patients with advanced prostatic carcinoma who relapsed androgen ablation.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:International Journal Of Cancer. - 88 : 4 (2000), p. 652-657. -
További szerzők:Nagy Attila Schally, Andrew Victor Sun, Baodong Groot, Kate Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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8.

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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9.

001-es BibID:BIBFORM033604
035-os BibID:WOS:000174171800020 PMID:11920625
Első szerző:Plonowski, Artur
Cím:Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity / Artur Plonowski, Jozsef L. Varga, Andrew V. Schally, Magdalena Krupa, Kate Groot, Gabor Halmos
Dátum:2002
ISSN:0020-7136
Megjegyzések:Vasoactive intestinal peptide (VIP) stimulates the proliferation and invasiveness of malignant prostatic cells. Receptors for VIP and the closely related growth hormone-releasing hormone (GH-RH) show considerable homology and are found in prostatic and other carcinomas. Among various analogs of GH-RH synthesized, JV-1-52 is a non-selective VIP/GH-RH antagonist, whereas JV-1-53 is a VIP antagonist devoid of GH-RH antagonistic effect. In our study, nude mice bearing PC-3 human androgen-independent prostate carcinomas were treated with JV-1-52 or JV-1-53 (20 mug/day, s.c.) for 28 days. Both antagonists produced a similar reduction in tumor volume (62-67%, p < 0.01) and tumor weight (59-62%; p < 0.05) vs. controls and extended tumor doubling-time from 9.1 to about 16 days (p < 0.05). To investigate the mechanisms involved, in another study we compared the effects of JV-1-53 with those of somatostatin analog RC-160. VIP antagonist JV-1-53 reduced tumor weight by 67% (p < 0.01) and suppressed the expression of mRNA for c-fos and c-jun oncogenes by about 34% (p < 0.05), without affecting serum levels of insulin-like growth factor-1 (IGF-1). In contrast, RC-160 (50 mug/day) reduced serum IGF-1 by 19% (p < 0.05), but did not significantly decrease tumor weight. mRNA for VIP and high affinity receptors for VIP were detected on PC-3 tumors. Our results suggest that VIP/GH-RH antagonists can inhibit the growth of androgen-independent prostate cancer by abrogating the autocrine/paracrine mitogenic stimuli of VIP. The ability of GH-RH antagonists to block tumoral VIP receptors, in addition to GH-RH receptors, could be potentially beneficial for prostate cancer therapy.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:International Journal Of Cancer. - 98 : 4 (2002), p. 624-629. -
További szerzők:Varga József L. Schally, Andrew Victor Krupa, Magdalena Groot, Kate Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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10.

001-es BibID:BIBFORM033603
035-os BibID:WOS:000177711200015 PMID:12126741
Első szerző:Plonowski, Artur
Cím:Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers / Artur Plonowski, Andrew V. Schally, Rebeca Busto, Magdalena Krupa, Jozsef L. Varga, Gabor Halmos
Dátum:2002
ISSN:0196-9781
Megjegyzések:The expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors in LNCaP, MDA-PCa-2b and PC-3 human prostate cancers grown in nude mice was investigated by RT-PCR. The expression of mRNA for GHRH was detected in LNCaP and PC-3, but not in MDA-PCa-2b prostatic carcinoma. RT-PCR analyses of mRNA isolated from LNCaP, MDA-PCa-2b and PC-3 cancers, revealed the presence of 720 and 566 bp products, corresponding to SV1 and SV2 isoforms of GHRH receptors. In PC-3 tumor membranes a radiolabeled GHRH antagonist [I-125]-JV-1-42 was bound to one class of high-affinity binding sites (K-d = 1.81 +/- 0.47 nM) and maximum binding capacity of 332.7 +/- 27.8 fmol/mg membrane protein. The in vivo uptake of [I-125]-JV-1-42 was observed in all xenografts of human prostate cancer, the tracer accumulation being the highest in PC-3 tumors. These results indicate that GHRH and SVs of its receptors, different from those found in the pituitary, are present in experimental human prostate cancers and may form a local mitogenic loop. The antiproliferative effects of GHRH antagonists on growth of prostate cancer could be exerted in part by an interference with this local GHRH system.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Peptides. - 23 : 6 (2002), p. 1127-1133. -
További szerzők:Schally, Andrew Victor Busto, Rebeca Krupa, Magdalena Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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Intézményi repozitóriumban (DEA) tárolt változat
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11.

001-es BibID:BIBFORM033718
Első szerző:Plonowski, Artur
Cím:Effective treatment of experimental DU-145 prostate cancers with targeted cytotoxic somatostatin analog AN-238 / Artur Plonowski, Andrew V. Schally, Attila Nagy, Baodong Sun, Gabor Halmos
Dátum:2002
Megjegyzések:We evaluated the effectiveness of targeted cytotoxic analog of somatostatin (SST) AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked covalently to SST octapeptide carrier RC-121 in DU-145 human androgen-independent prostate cancers xenografted into nude mice. We also investigated the expression of mRNAs for SST receptor subtypes 2A and 5 (sst2A and sst5) in DU-145 tumors. After 8 weeks of treatment, AN-238 practically arrested the proliferation of DU-145 cancers. The tumor volume in nude mice that received 4 injections of AN-238 at the dose of 150 nmol/kg was 63.4+/-6.7 mm3, nearly 4 times smaller than that in controls which measured 249.1+/-36.3 mm3 (p<0.001). Treatment with AN-238 lowered tumor weight by 68% (p<0.01) compared with the control group and extended the tumor volume doubling time to 184.1+/-69.4 days, versus 32.1+/-6.6 days in controls (p<0.05). No toxicity-related deaths occurred during treatment with AN-238. Cytotoxic radical AN-201 administered alone or in an unconjugated mixture with carrier RC-121 inhibited the growth of DU-145 tumors only after the third and fourth injection and was toxic. The expression of mRNA for sst2A and sst5 was detected in all specimens of control DU-145 tumors and in tumors treated with AN-238. The present study demonstrates the high efficacy of SST-receptor-targeted chemotherapy in a model of human androgen-independent prostatic carcinoma.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:International Journal of Oncology. - 20 : 2 (2002), p. 397-402. -
További szerzők:Schally, Andrew Victor Nagy Attila Sun, Baodong Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM033614
035-os BibID:PMID:11390017 WOS:000169181800005
Első szerző:Rékási Zoltán
Cím:Antiproliferative actions of growth hormone-releasing hormone antagonists on MiaPaCa-2 human pancreatic cancer cells involve cAMP independent pathways / Zoltan Rekasi, Jozsef L. Varga, Andrew V. Schally, Artur Plonowski, Gabor Halmos, Balazs Csernus, Patricia Armatis, Kate Groot
Dátum:2001
ISSN:0196-9781
Megjegyzések:We evaluated the effects of GHRH antagonists on the proliferation of MiaPaCa-2 human pancreatic cancer cells and cAMP signaling in vitro. GHRH antagonists inhibited the proliferation of MiaPaCa-2 cells in vitro in a dose-dependent way and caused a significant elevation in cAMP production. In a superfusion system, short-term exposure of the cells to GHRH antagonists evoked an acute, dose-dependent release of cAMP into the medium. Native GHRH, which stimulates cAMP efflux from pituitary at nanomolar doses, did not influence cAMP release from cultured or superfused MiaPaCa-2 cells even at 10-30 microM. VIP, PACAP, secretin and glucagon also did not influence cell proliferation or cAMP production. Adenylate cyclase activator forskolin (FSK) caused a greater cAMP response, but a smaller antiproliferative effect than GHRH antagonists. Combined treatment with FSK and GHRH antagonist JV-1-38 potentiated the cAMP-inducing effect of FSK, but did not produce a greater inhibition of cell proliferation than JV-1-38 alone. A selective accumulation of radiolabeled GHRH antagonist [(125)I]JV-1-42 in vivo in MiaPaCa-2 carcinoma xenografted into nude mice was also observed. In conclusion, second messengers other than cAMP participate in the signal transduction pathways of GHRH analogs mediated by tumoral GHRH receptors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Peptides. - 22 : 6 (2001), p. 879-886. -
További szerzők:Varga József L. Schally, Andrew Victor Plonowski, Artur Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Csernus Balázs Armatis, Patricia Groot, Kate
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Intézményi repozitóriumban (DEA) tárolt változat
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