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1.

001-es BibID:BIBFORM033616
035-os BibID:PMID:11344219 WOS:000168731600050
Első szerző:Chatzistamou, Ioulia
Cím:Antagonists of growth hormone-releasing hormone and somatostatin analog RC-160 inhibit the growth of the OV-1063 human epithelial ovarian cancer cell line xenografted into nude mice / Ioulia Chatzistamou, Andrew V. Schally, Jozsef L. Varga, Kate Groot, Patricia Armatis, Rebeca Busto, Gabor Halmos
Dátum:2001
ISSN:0021-972X
Megjegyzések:The effects of antagonists of GHRH and the somatostatin analog RC-160 on the growth of OV-1063 human epithelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20 microg/day of the GHRH antagonist JV-1-36 or MZ-5-156 and 60 microg/day of the somatostatin analog RC-160 for 25 days decreased tumor volume by 70.9% (P < 0.01), 58.3% (P < 0.05), and 60.6% (P < 0.01), respectively, vs. the control value. The levels of GH in serum were decreased in all of the treated groups, but only RC-160 significantly reduced serum insulin-like growth factor I (IGF-I). The levels of messenger ribonucleic acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were investigated by multiplex RT-PCR. No expression of mRNA for IGF-I was detected, but treatment with JV-1-136 caused a 51.8% decrease (P < 0.05) in the level of mRNA for IGF-II in tumors. Exposure of OV-1063 cells cultured in vitro to GHRH, IGF-I, or IGF-II significantly (P < 0.05) stimulated cell growth, but 10(-5) mol/L JV-1-36 nearly completely inhibited (P < 0.001) OV-1063 cell proliferation. OV-1063 tumors expressed mRNA for GHRH receptors and showed the presence of binding sites for GHRH. Our results indicate that antagonistic analogs of GHRH and the somatostatin analog RC-160 inhibit the growth of epithelial ovarian cancers. The effects of RC-160 seem to be exerted more on the pituitary GH-hepatic IGF-I axis, whereas GHRH antagonists appear to reduce IGF-II production and interfere with the autocrine regulatory pathway. The antitumorigenic action of GHRH antagonists appears to be mediated by GHRH receptors found in OV-1063 tumors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal Of Clinical Endocrinology & Metabolism. - 86 : 5 (2001), p. 2144-2152. -
További szerzők:Schally, Andrew Victor Varga József L. Groot, Kate Armatis, Patricia Busto, Rebeca Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM033578
035-os BibID:PMID:15784701 WOS:000229351000068
Első szerző:Engel, Jörg B.
Cím:Inhibition of growth of experimental human endometrial cancer by an antagonist of growth hormone-releasing hormone / Jörg B. Engel, Gunhild Keller, Andrew V. Schally, Gabor L. Toller, Kate Groot, Alexandre Havt, Patricia Armatis, Marta Zarandi, Jozsef L. Varga, Gabor Halmos
Dátum:2005
ISSN:0021-972X
Megjegyzések:Antagonists of GHRH are being developed for the treatment of various cancers. In this study we investigated in vivo and in vitro the effects of the GHRH antagonist MZ-J-7-118 and its mechanism of action in HEC-1A human endometrial cancer. Treatment of nude mice bearing HEC-1A xenografts with 10 mug/d MZ-J-7-118 for 6 wk significantly inhibited the volume of HEC-1A tumors by 43%, tumor weight by 40% compared with controls and prolonged the tumor doubling time from 18.7 +/- 1.4 to 25.4 +/- 3.8 d. Administration of 20 mug MZ-J-7-118, sc, twice a day significantly (P < 0.05) decreased HEC-1A growth, as evidenced by a 57.9% decrease in tumor volume, a 50.7% reduction in tumor weight, and the extension of tumor doubling time from 17.5 +/- 2.8 to 36.4 +/- 6.5 d. Therapy with GHRH antagonists significantly decreased serum IGF-I levels in experiment 1, and significantly increased tumoral IGF-I levels in experiment 2 in treated mice. Levels of IGF-II and vascular endothelial growth factor-A in tumors were not changed. Specific high affinity binding sites for GHRH were found on HEC-1A tumor membranes using ligand competition assays with (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-118 displaced radiolabeled JV-1-42 with an IC(50) of 0.13 +/- 0.04 nm. The expression of mRNA for GHRH and splice variants of the GHRH receptor in HEC-1A tumors was demonstrated by real-time RT-PCR analysis. HEC-1A cells cultured in vitro secreted GHRH into the medium. The GHRH antagonist MZ-J-7-118 inhibited the growth of HEC-1A cells in vitro. Our results indicate that GHRH antagonists can reduce the growth of human endometrial cancer and could be used as an alternative adjuvant therapy for the management of endometrial cancer.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal Of Clinical Endocrinology & Metabolism. - 90 : 6 (2005), p. 3614-3621. -
További szerzők:Keller, Gunhild Schally, Andrew Victor Toller Gábor L. Groot, Kate Havt, Alexandre Armatis, Patricia Zarándi Márta Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

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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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM033633
035-os BibID:WOS:000089820800004
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Human ovarian cancers express somatostatin receptors / Gábor Halmos, Baodong Sun, Andrew V. Schally, Francine Hebert, Attila Nagy
Dátum:2000
ISSN:0021-972X
Megjegyzések:Characteristics of receptors for somatostatin (SST) analog RC-160 on 17 surgical specimens of human epithelial ovarian cancer and two human ovarian cancer lines were determined by ligand competition assays. The expression of mRNA for four SST receptor subtypes (sst(1), sst(2A), sst(3) and sst(5)) was investigated by RT-PCR. Thirteen of 17 specimens (76%) exhibited high affinity binding sites for RC-160 with K(d) = 6.55 nmol/L and a B(max) = 575.4 fmol/mg membrane protein. Specific receptors for RC-160 were also found in xenografts of OV-1063 and UCI-107 human ovarian cancer lines. The mRNA for sst(1) was detected in 65% of the ovarian cancer specimens, while the incidence of sst(2A), sst(3) and sst(5) was 65%, 41% and 24%, respectively. Both ovarian cancer cell lines also expressed mRNA for these four subtypes. The presence of these SST receptor subtypes in human ovarian cancers allows the use of SST analogs and their radionuclide and cytotoxic derivatives for the diagnosis and treatment of this malignancy.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal of Clinical Endocrinology & Metabolism. - 85 : 10 (2000), p. 3509-3512. -
További szerzők:Sun, Baodong Schally, Andrew Victor Hebert, Francine Nagy Attila
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Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM033602
035-os BibID:PMID:12364462 WOS:000178649800050
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer / Gabor Halmos, Andrew V. Schally, Tamas Czompoly, Magdalena Krupa, Jozsef L. Varga, Zoltan Rekasi
Dátum:2002
ISSN:0021-972X
Megjegyzések:Antagonists of GHRH inhibit the growth of various human tumors, including prostate cancer, but the tumoral receptors mediating the antiproliferative effect of GHRH antagonists have not been clearly identified. Recently, we demonstrated that human cancer cell lines express splice variants (SVs) of receptors for GHRH, of which SV1 exhibits the greatest similarity to the pituitary GHRH receptors. In this study we investigated the expression of GHRH and SVs of GHRH receptor and the binding characteristics of the GHRH receptor isoform in 20 surgical specimens of organ-confined and locally advanced human prostatic adenocarcinomas. The mRNA expression of GHRH and SVs of GHRH receptor was investigated by RT-PCR. The affinity and density of receptors for GHRH were determined by ligand competition assays based on binding of (125)I-labeled GHRH antagonist JV-1-42 to tumor membranes. Twelve of 20 tumors (60%) exhibited specific, high affinity binding for JV-1-42, with a mean dissociation constant (K(d)) of 0.81 nmol/liter and a mean maximal binding capacity of 185.2 fmol/mg membrane protein. The mRNA of SV1 was detected in 13 of 20 (65%) prostate cancer specimens and was consistent with the presence of GHRH binding. RT-PCR analyses also revealed the expression of mRNA for GHRH in 13 of 15 (86%) prostatic carcinoma specimens examined. The presence of GHRH and its tumoral receptor SVs in prostate cancers suggests the possible existence of an autocrine mitogenic loop. The antitumor effects of GHRH antagonists in prostate cancer could be exerted in part by interference with this local GHRH system.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal of Clinical Endocrinology & Metabolism. - 87 : 10 (2002), p. 4707-4714. -
További szerzők:Schally, Andrew Victor Czompoly Tamás Krupa, Magdalena Varga József L. Rékási Zoltán
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Intézményi repozitóriumban (DEA) tárolt változat
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6.

001-es BibID:BIBFORM033817
035-os BibID:PMID:8940358 WOS:A1996VU35100026
Első szerző:Kovács Magdolna
Cím:Effects of acute and chronic administration of a new potent antagonist of growth hormone-releasing hormone in rats : mechanisms of action / Magdolna Kovács, Márta Zarándi, Gábor Halmos, Kate Groot, Andrew V. Schally
Dátum:1996
ISSN:0013-7227
Megjegyzések:Antagonistic analogs of human GH-releasing hormone (hGHRH) are potential candidates for the treatment of disorders characterized by excessive GH secretion and especially for therapy of GH- and insulin-like growth factor (IGF)-dependent tumors. These analogs should be also useful for the studies on the mechanism of action of GHRH. In the present investigation, we evaluated the effects of chronic i.m. administration of a new potent GHRH antagonist (Ibu0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27)hGHRH(1-28)+ ++Agm (MZ-4-71) on the growth rate, serum GH, and IGF-I concentration, GH responsiveness to exogenous GHRH, as well as the pituitary GH content and GHRH receptor concentration in young female rats. We also studied the consequences of acute, high-dose i.v. application of this antagonist on the basal GH and IGF-I levels in adult male rats. In addition, the ability of GHRH antagonist MZ-4-71 to prevent GH release induced by GHRH pulses was determined in vitro in the superfused rat pituitary cell system. Chronic treatment in vivo using twice daily i.m. injections of 20 microg MZ-4-71 for 2 weeks reduced the rate of increase in body weight by 21% and in body length of young rats by 36%, as compared with controls. GH responses to bolus injections of GHRH declined by 22%, and serum IGF-I concentrations by 15% at the end of the treatment. The total pituitary GH content, but not relative GH concentration, also decreased by 15% and GHRH receptor concentration by 48%, following chronic treatment with this antagonist. Bolus injections of high doses of MZ-4-71 (400 microg i.v.) induced a marked and protracted (6 h) inhibition of the basal serum GH concentration and a parallel inhibition of the serum IGF-I levels. The nadir of both the serum GH (62% decrease) and the IGF-I level (30% decrease) was found at 3 h after the injection. In vitro studies showed that MZ-4-71 was able to dose-dependently inhibit the GH-releasing effect of GHRH pulses. Present results demonstrate that GHRH antagonist MZ-4-71 is effective in vivo and that it can inhibit growth and secretion of GH and IGF-I in rats. Our findings also provide new information on the role of GHRH in regulating synthesis of GH and GHRH receptors. It is likely that antagonistic analogs of GHRH could find clinical application for reducing the growth of tumors dependent on GH or IGF-I.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrinology. - 137 : 12 (1996), p. 5364-5369. -
További szerzők:Zarándi Márta Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Schally, Andrew Victor
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Intézményi repozitóriumban (DEA) tárolt változat
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7.

001-es BibID:BIBFORM033904
035-os BibID:WOS:A1993MG13600051
Első szerző:Pinski, Jacek
Cím:Inhibition of growth of the human malignant glioma cell line (U87MG) by the steroid hormone antagonist RU486 / Jacek Pinski, Gabor Halmos, Yutaka Shirahige, James L. Wittliff, Andrew V. Schally
Dátum:1993
ISSN:0021-972X
Megjegyzések:Treatment of nude mice bearing xenografts of the human malignant glioma U87MG cell line with the steroid hormone antagonist RU486 for 4 weeks resulted in a significant and dose-dependent suppression of tumor volume and weight. Receptor analyses of tumor cytosol preparations demonstrated a single class of high affinity binding sites for dexamethasone, but the absence of receptors for progesterone. RU486 also nullified the stimulatory effect of dexamethasone on proliferation of U87MG cells in vitro. These results indicate that the growth of U87MG human malignant glioma is dependent on corticoids. The antiproliferative effect of RU486 appears to be due to the inhibition of binding of glucocorticoid hormones to their receptor proteins. Our results suggest a new therapy for some brain tumors, such as malignant gliomas based on the steroid hormone antagonist RU486.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Journal of Clinical Endocrinology & Metabolism. - 77 : 5 (1993), p. 1388-1392. -
További szerzők:Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Shirahige, Yutaka Wittliff, James L. Schally, Andrew Victor
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Intézményi repozitóriumban (DEA) tárolt változat
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8.

001-es BibID:BIBFORM033823
035-os BibID:PMID:8754771 WOS:A1996UY11100040
Első szerző:Pinski, Jacek
Cím:Chronic administration of the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix decreases gonadotrope responsiveness and pituitary LHRH receptor messenger ribonucleic acid levels in rats / Jacek Pinski, Najib Lamharzi, Gábor Halmos, Kate Groot, Andreas Jungwirth, Manuel Vadillo-Buenfil, Sham S. Kakar, Andrew V. Schally
Dátum:1996
ISSN:0013-7227
Megjegyzések:Continuous exposure to LHRH or its agonistic analogs results in a reduction of LHRH receptor sites and messenger RNA (mRNA) transcripts as well as in desensitization of the pituitary gonadotropes. To determine, whether LHRH antagonists might be similar in this respect to the agonists, we treated male rats for 4 weeks with daily sc injections of LHRH antagonist [Ac-D-Nal2,Phe(4Cl)2,D-Pal(3)3, D-Cit6,D-Ala10]LHRH (Cetrorelix acetate) or LHRH agonist, [D-Trp6]LHRH, in doses of 100 micrograms/animal-day. Another group of rats received a single im injection of 4.5 mg Cetrorelix pamoate depot, a sustained delivery formulation of the LHRH antagonist. An iv stimulation test with LHRH (200 ng/rat) was performed after 4 weeks of treatment. The rats were killed, and pituitary LHRH receptor characteristics were measured by RRA. To examine the effect of LHRH antagonist treatment on the expression of the pituitary LHRH receptor gene, some of the rats injected with Cetrorelix pamoate depot were killed after 2 weeks, and levels of LHRH receptor mRNA were determined by Northern blot and dot blot hybridization to a 32P-labeled rat complementary DNA probe. Our data show that LHRH-stimulated LH secretion at 30 min was suppressed by approximately 33% (P < 0.01) in rats pretreated with [D-Trp6]LHRH compared to that in animals injected with LHRH alone. Pretreatment of the rats with the LHRH antagonist suppressed the LH response to LHRH more markedly, the LH levels at 30 min were decreased by 89.8% and 96% in groups treated with Cetrorelix acetate and Cetrorelix pamoate depot, respectively. The testosterone response was virtually abolished in groups receiving Cetrorelix. The concentration of pituitary receptors for LHRH fell by 69% in the [D-Trp6]LHRH group, whereas the reductions in the Cetrorelix acetate group and in the group that received Cetrorelix pamoate depot were 77% and 82%, respectively. Treatment with Cetrorelix pamoate depot led to a 75-80% decrease in the levels of 5.0- and 4.5-kilobase forms of LHRH receptor mRNA compared to those in the control group. Dot blot analysis also showed 83% reduction in the mRNA for LHRH receptor. In conclusion, these data demonstrate that prolonged administration of LHRH antagonists such as Cetrorelix causes an impairment of gonadotropin secretion and a marked decrease in the levels of LHRH receptors as well as in the expression of the LHRH receptor gene. Thus, the down-regulation of pituitary LHRH receptors produced by LHRH antagonists appears to be similar to that resulting from the agonists.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrinology. - 137 : 8 (1996), p. 3430-3436. -
További szerzők:Lamharzi, Najib Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Jungwirth, Andreas Vadillo-Buenfil, Manuel Kakar, Sham S. Schally, Andrew Victor
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM033636
035-os BibID:PMID:10830299 WOS:000088386100031
Első szerző:Rékási Zoltán
Cím:Antagonists of growth hormone-releasing hormone and vasoactive intestinal peptide inhibit tumor proliferation by different mechanisms : evidence from in vitro studies on human prostatic and pancreatic cancers / Zoltan Rekasi, Jozsef L. Varga, Andrew V. Schally, Gabor Halmos, Patricia Armatis, Kate Groot, Tamas Czompoly
Dátum:2000
ISSN:0013-7227
Megjegyzések:Antagonists of GH-releasing hormone (GHRH) and vasoactive intestinal peptide (VIP) inhibit the proliferation of various tumors in vitro and in vivo, but a comparison of their antitumor effects and mechanisms of action has not been reported to date. We recently synthesized and characterized a series of analogs, some of which are primarily GHRH antagonists (JV-1-36, JV-1-38, and JV-1-42), whereas others are more selective for VIP receptors (VPAC-R; JV-1-50, JV-1-51, JV-1-52, and JV-1-53). LNCaP human prostatic cancer cells express VPAC-R, with predominant subtype 1 determined by RT-PCR. Our studies show that GHRH antagonists significantly inhibit the proliferation of both VPAC-R positive LNCaP cells (P < 0.001) and VPAC-R negative MiaPaCa-2 human pancreatic cancer cells cultured in vitro (P < 0.05 to P < 0.001). Growth inhibition of LNCaP cells is accompanied by a proportional reduction in prostate-specific antigen (PSA) secretion (P < 0.001). In a superfusion system, the inhibitory activities of the analogs on the rate of VIP and GHRH-induced PSA secretion correlate well with their VPAC-R binding affinities to LNCaP cell membranes. Antagonists more selective for VPAC-R display a stronger inhibition of inducible PSA release than GHRH antagonists, but have smaller effects or no effects on proliferation and PSA secretion in culture. Collectively, our findings demonstrate that the antiproliferative activity of the analogs on cancer cells is not correlated to their VPAC-R antagonistic potencies. Because GHRH antagonists inhibit the proliferation of LNCaP cells more powerfully than VPAC-R antagonists and also suppress the growth ofVPAC-R-negative MiaPaCa-2 cells, it can be concluded that their antiproliferative effect is exerted through a mechanism independent of VPAC-R.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrinology. - 141 : 6 (2000), p. 2120-2128. -
További szerzők:Varga József L. Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Armatis, Patricia Groot, Kate Czompoly Tamás
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM033610
035-os BibID:PMID:11564700 WOS:000171238700027
Első szerző:Szepesházi Károly
Cím:Antagonists of GHRH decrease production of GH and IGF-I in MXT mouse mammary cancers and inhibit tumor growth / Karoly Szepeshazi, Andrew V. Schally, Patricia Armatis, Kate Groot, Francine Hebert, Anita Feil, Jozsef L. Varga, Gabor Halmos
Dátum:2001
ISSN:0013-7227
Megjegyzések:The involvement of IGF-I in mammary carcinogenesis is well established, but the role of GH, as an autocrine growth factor for breast cancers is poorly understood. The goal of our study was to investigate whether antagonists of GHRH can interfere with the effects of GH and IGF-I in MXT mouse mammary cancers. GHRH antagonists JV-1-36 and JV-1-38 inhibited growth of estrogen-independent MXT mouse mammary cancers in vivo, producing about 50% reduction in tumor volume (P < 0.05). This growth inhibition was associated with a decrease in cell proliferation and an increase in apoptosis in MXT cancers. RIA and RT- PCR analyses showed that the concentrations of GH and IGF-I and the levels of mRNA for GH and IGF-I in MXT tumors were reduced by the therapy with GHRH antagonists. Messenger RNA for GH receptors was also decreased. In vitro, the proliferation of MXT cancer cells was strongly stimulated by GH and less effectively by IGF-I, indicating that both GH and IGF-I may act as growth factors for this mammary carcinoma. GHRH antagonist JV-1-38 inhibited the autonomous growth of MXT cells and the proliferation induced by IGF-I or GH and diminished (3)H-thymidine-incorporation stimulated by IGF-I and GH. These findings and a sustained increase in cyclin B2 concentrations in the cells shown by immunoblotting indicate that JV-1-38 causes a block at the end of the G(2) phase of cell cycle. Our results demonstrate that GHRH antagonists decrease the local production of both GH and IGF-I in MXT mouse mammary cancers, the resulting growth inhibition being the consequence of reduced cell proliferation and increased apoptosis.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrinology. - 142 : 10 (2001), p. 4371-4378. -
További szerzők:Schally, Andrew Victor Armatis, Patricia Groot, Kate Hebert, Francine Feil, Anita Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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Intézményi repozitóriumban (DEA) tárolt változat
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