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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)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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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
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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