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1.

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
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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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2.

001-es BibID:BIBFORM033617
035-os BibID:WOS:000168134500023
Első szerző:Kiaris, Hippokratis
Cím:A targeted cytotoxic somatostatin (SST) analogue, AN-238, inhibits the growth of H-69 small-cell lung carcinoma (SCLC) and H-157 non-SCLC in nude mice / H. Kiaris, A. V. Schally, A. Nagy, K. Szepeshazi, F. Hebert, G. Halmos
Dátum:2001
ISSN:0959-8049
Megjegyzések:Recently. we developed a cytotoxic analogue of somatostatin (SST), AN-238, in which the SST carrier peptide RC-121 was linked to 2-pyrrolinodoxorubicin (2-pyrrolino-DOX) (AN-201), a potent derivative of doxorubicin. AN-238 can be targeted to SST receptors (SSTRs) on tumours. In the present study, we evaluated the effects of AN-238 on the growth of H-69 small-cell lung carcinoma (SCLC) and H-157 non-SCLC xenografted into nude mice. High affinity binding sites for SST are present in H-69 SCLC and were now detected in H-157 non-SCLC xenografts, but not in H-157 cells. A strong expression of the human SSTR subtype 2 (hSSTR-2) and a weaker expression of subtype 5 (hSSTR-5) was found in H-69 SCLC cells, but not in H-157 non-SCLC cells. However, a strong expression of mRNA for mouse (m)SSTR-2 could be detected in H-157 xenografts. AN-238 effectively inhibited the growth of H-69 SCLC tumours in nude mice. Twenty-six days after a single injection of AN-238 at 200 nmol/kg. the volume of H-69 rumours was decreased by approximately 55% (P < 0.05) compared with the controls, while AN-201 at the same dose was highly toxic and produced only a minor tumour inhibition. To evaluate the potency of multiple doses of AN-238, nude mice bearing H-69 SCLC received three injections of AN-238 at 150 nmol/kg on days 1, 12 and 28. In the period of 42 days after the first injection, the growth rate of H-69 tumours was approximately 50% lower than that of controls. In nude mice bearing H-157 non-SCLC tumours. a single i.v. administration of AN-238 at 200 nmol/kg inhibited tumour volume by 91% after 28 days (P < 0.01 compared with controls). AN-201 was toxic and ineffective at the same dose. Two injections of AN-238 at 150 nmol/kg given on days 1 and 18 produced 83% inhibition of H-157 tumour growth (P < 0.01 versus controls). AN-238 given as a single dose of 200 nmol/kg induced necrosis. while two injections of 150 nmol/kg induced apoptosis in the tumour tissue. Our results indicate that targeted cytotoxic SST analogue AN-238 could he considered for therapy of both SCLC and non-SCLC.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:European Journal of Cancer. - 37 : 5 (2001), p. 620-628. -
További szerzők:Schally, Andrew Victor Nagy Attila Szepesházi Károly Hebert, Francine Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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3.

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
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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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4.

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
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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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5.

001-es BibID:BIBFORM033652
Első szerző:Szepesházi Károly
Cím:Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers / K. Szepeshazi, A. V. Schally, K. Groot, P. Armatis, G. Halmos, F. Hebert, B. Szende, J. L. Varga, M. Zarandi
Dátum:2000
Megjegyzések:Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 microg intraperitoneally or 5 microg subcutaneously (s.c.) resulted in a significant 43-45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 microg s.c. produced a 43-58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that HT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of HT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:British Journal of Cancer. - 82 : 10 (2000), p. 1724-1731. -
További szerzők:Schally, Andrew Victor Groot, Kate Armatis, Patricia Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Hebert, Francine Szende Béla Varga József L. Zarándi Márta
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6.

001-es BibID:BIBFORM033613
035-os BibID:WOS:000171031400036 PMID:11555603
Első szerző:Szepesházi Károly
Cím:Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers / Karoly Szepeshazi, Andrew V. Schally, Gabor Halmos, Baodong Sun, Francine Hebert, Balazs Csernus, Attila Nagy
Dátum:2001
Megjegyzések:Abstract: Purpose: The expression of somatostatin receptors (SSTRs) allows the localization and treatment of some tumors with radiolabeled SST analogues. We investigated whether SSTRs on human pancreatic cancer lines xenografted into nude mice can be used for targeting of cytotoxic somatostatin analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to octapeptide carrier RC-121. Experimental Design: AN-238 and AN-201 were administered i.v. to nude mice bearing SW-1990 pancreatic cancers. Tumor growth reduction and survival were analyzed, and cell proliferation and apoptosis were determined with histological methods. The effects of repeated administration of AN-238 and AN-201 were also evaluated on xenografted Panc-1, MiaPaCa-2, CFPAC-1, Capan-1, and Capan-2 pancreatic cancers. The expression of mRNA for SSTR subtypes 2A, 3, and 5 in tumors was analyzed by reverse transcription-PCR, and binding assays were performed. Results: All of the cancer models except MiaPaCa-2 displayed functional receptors for SST. SW-1990 expressed mRNA for SSTR subtypes 3 and 5, whereas various patterns of subtypes 2A, 3, and 5 were found in other pancreatic cancers. Repeated administration of AN-238 at 150 nmol/kg significantly inhibited growth of SW-1990 cancers (93% after 45 days; P = 0.016) and other tumors but not MiaPaCa-2. AN-201 was toxic and less effective. The efficacy of AN-238 was consistent with SSTR expression. Conclusions: Growth of experimental human pancreatic cancers that express SSTRs can be inhibited by cytotoxic somatostatin analogue AN-238.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Clinical Cancer Research. - 7 : 9 (2001), p. 2854-2861. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Sun, Baodong Hebert, Francine Csernus Balázs Nagy Attila
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7.

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
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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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8.

001-es BibID:BIBFORM033653
Első szerző:Szepesházi Károly
Cím:Antagonists of growth hormone-releasing hormone (GH-RH) inhibit in vivo proliferation of experimental pancreatic cancers and decrease IGF-II levels in tumours / K. Szepeshazi, A. V. Schally, K. Groot, P. Armatis, F. Hebert, G. Halmos
Dátum:2000
ISSN:0959-8049
Megjegyzések:Insulin-like growth factors (IGF-I and IGF-II) are implicated in the pathogenesis of pancreatic carcinoma. Antagonists of growth hormone-releasing hormone (GH-RH) suppress the GH-RH-GH-IGF-I axis and also act directly on tumours to reduce production of IGF-I or II. The aim of this study was to investigate the effects of two potent GH-RH antagonists in two experimental models of pancreatic cancer. Syrian golden hamsters with nitrosamine-induced pancreatic tumours were treated with 10 micrograms/day of GH-RH antagonist MZ-4-71 for 60 days. The therapy reduced the number of tumorous animals, decreased the weight of tumorous pancreata by 55%, and lowered AgNOR numbers in tumour cells. In two other experiments, GH-RH antagonists MZ-4-71 and MZ-5-156 significantly inhibited growth of SW-1990 human pancreatic cancers xenografted into nude mice, as shown by a reduction in tumour volume and tumour weights, and a decrease in AgNORs in cancer cells. IGF-I levels in serum and in pancreatic cancer tissue remained unchanged after therapy, suggesting that an effect on IGF-I is not involved in tumour inhibition. In contrast, IGF-II concentrations in tumours were significantly reduced by 50-60% after treatment with the GH-RH antagonists as compared with controls. In vitro studies showed that the concentration of IGF-II in the culture medium was increased after seeding of SW-1990 cells, indicating that this pancreatic cancer cell line produced and released IGF-II. This finding was also supported by the expression of IGF-II mRNA in the SW-1990 cells. Addition of 3 x 10(-6) M of GH-RH antagonist MZ-5-156 to the reduced-serum medium decreased cell proliferation, IGF-II mRNA expression in the cells and IGF-II concentration in the medium. Our findings indicate that inhibitory effects of GH-RH antagonists on the growth of experimental pancreatic cancers, may result from a decrease in the production and concentration of IGF-II in the tumours.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:European Journal of Cancer. - 36 : 1 (2000), p. 128-136. -
További szerzők:Schally, Andrew Victor Groot, Kate Armatis, Patricia Hebert, Francine Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
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9.

001-es BibID:BIBFORM033605
035-os BibID:PMID:11830533 WOS:000173740600026
Első szerző:Szepesházi Károly
Cím:Targeted cytotoxic somatostatin analogue AN-238 inhibits somatostatin receptor-positive experimental colon cancers independently of their p53 status / Karoly Szepeshazi, Andrew V. Schally, Gabor Halmos, Patricia Armatis, Francine Hebert, Baodong Sun, Anita Feil, Hippokratis Kiaris, Attila Nagy
Dátum:2002
Megjegyzések:The resistance of advanced colorectal cancers to therapy is often related to mutations in the p53 tumor suppressor gene. Because somatostatin (SRIF) receptors (ssts) are present in colorectal carcinomas, the treatment with targeted cytotoxic SRIF analogue AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to octapeptide SRIF carrier RC-121, may overcome this resistance by producing a higher concentration of the cytotoxic agent in the tumors. Four colon cancer cell lines, HCT-116 and LoVo expressing wild-type p53, and HCT-15 and HT-29 with mutated p53, were investigated. HCT-116, HCT-15, and HT-29, but not LoVo possess functional ssts. We analyzed changes in p53, p21, and proliferating cell nuclear antigen (PCNA) concentrations in these cells in vitro by immunoblotting after exposure to AN-238, its radical AN-201, or doxorubicin (DOX). Equitoxic doses of AN-238, AN-201, or DOX affected p53, p21, and PCNA differently. Analysis of the p21:p53 ratios revealed that DOX increased p53 levels, but most of p53 was mutated and inactive, whereas AN-238 produced smaller changes in p53 concentrations but enhanced its activity. In HCT-15 cells, PCNA:p21 ratios, which are indicators of proliferation and repair processes, remained unchanged after exposure to AN-238 but were increased by DOX. In vivo studies in nude mice demonstrated that AN-238, AN-201, and DOX were equally effective on HCT-116 tumors that express wild-type p53. However, AN-238 also inhibited the growth of HCT-15 and HT-29 cancers that express mutant p53, whereas AN-201 and DOX showed no effect. None of the compounds could suppress the proliferation of LoVo tumors that lack functional ssts. In conclusion, cytotoxic SRIF analogue AN-238 inhibits the growth of experimental colon cancers that express ssts, regardless of their p53 status.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer Research. - 62 : 3 (2002), p. 781-788. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Armatis, Patricia Hebert, Francine Sun, Baodong Feil, Anita Kiaris, Hippokratis Nagy Attila
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10.

001-es BibID:BIBFORM033595
035-os BibID:PMID:14633721 WOS:000186770700057
Első szerző:Szereday Zoltán
Cím:Antagonists of growth hormone-releasing hormone inhibit the proliferation of experimental non-small cell lung carcinoma / Zoltan Szereday, Andrew V. Schally, Jozsef L. Varga, Celia A. Kanashiro, Francine Hebert, Patricia Armatis, Kate Groot, Karoly Szepeshazi, Gabor Halmos, Rebeca Busto
Dátum:2003
ISSN:0008-5472
Megjegyzések:Recent studies show that antagonists of growth hormone-releasing hormone (GH-RH) inhibit proliferation of various cancers indirectly through blockage of the endocrine GH-insulin-like growth factor (IGF) I axis and directly by an action on tumor cells involving the suppression of autocrine/paracrine IGF-I, IGF-II, or GH-RH. The effectiveness of therapy with GH-RH antagonist JV-1-38 and its mechanisms of action were investigated in NCI-H838 non-small cell lung carcinoma (NSCLC) xenografted s.c. into nude mice and in vitro. Treatment with GH-RH antagonist JV-1-38 significantly (P < 0.05-0.001) inhibited tumor growth as demonstrated by a 58% decrease in final tumor volume, 54% reduction in tumor weight, and the extension of tumor-doubling time from 8.5 +/- 1.38 to 12 +/- 1.07 days as compared with controls. Using ligand competition assays with (125)I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-PCR revealed the expression of mRNA for GH-RH and splice variant 1 (SV(1)) of GH-RH receptor in H838 tumors. Reverse transcription-PCR analysis also demonstrated that H838 tumors express IGF-I and IGF-I receptors. Tumoral concentration of IGF-I and its mRNA expression were significantly decreased by 25% (P = 0.05) and 65% (P < 0.001), respectively, in animals receiving JV-1-38, whereas serum IGF-I levels remained unchanged. In vitro studies showed that H838 cells secreted GH-RH and IGF-I into the medium. The growth of tumor cells in vitro was stimulated by IGF-I and inhibited by GH-RH antagonist JV-1-38 and a GH-RH antiserum. Our results extend the findings on the involvement of IGF-I in NSCLC and suggest that GH-RH may be an autocrine growth factor for H838 NSCLC. The antitumorigenic action of GH-RH antagonists could be partly direct and mediated by SV(1) of tumoral GH-RH receptors. The finding of GH-RH and SV(1) of GH-RH receptors in NSCLC provides a new approach to the treatment of this malignancy based on the use of antagonistic analogues of GH-RH.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Cancer Research. - 63 : 22 (2003), p. 7913-7919. -
További szerzők:Schally, Andrew Victor Varga József L. Kanashiro, Celia A. Hebert, Francine Armatis, Patricia Groot, Kate Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Busto, Rebeca
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11.

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
külföldön készült közlemény
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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