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001-es BibID:	BIBFORM047176
035-os BibID:	PMID:23744510
Első szerző:	Szepesházi Károly
Cím:	Powerful Inhibition of Experimental Human Pancreatic Cancers by Receptor Targeted Cytotoxic LH-RH analog AEZS-108 / Karoly Szepeshazi, Andrew V. Schally, Norman L. Block, Gabor Halmos, Mehrdad Nadji, Luca Szalontay, Irving Vidaurre, Andrew Abi-Chaker, Ferenc G. Rick
Dátum:	2013
Megjegyzések:	Pancreatic carcinoma is one of the cancers with the worse prognosis, thus any therapeutic improvement is imperative. Cytotoxic LH-RH analog, AN-152 (proprietary designation, AEZS-108), consisting of doxorubicin (DOX) conjugated to D-Lys6LH-RH, is now in clinical trials for targeted therapy of several sex hormone-dependent tumors that express LH-RH receptors. We investigated LH-RH receptors in human pancreatic carcinoma and the effects of AN-152 (AEZS-108) on experimental pancreatic cancers. We determined LH-RH receptor presence in human pancreatic cancer samples by immunohistochemistry and, in three human pancreatic cancer lines (SW-1990, Panc-1 and CFPAC-1), by binding assays and Western blotting. The effects of the cytotoxic LH-RH analog were investigated on growth of these same cancer lines xenografted into nude mice. We also analyzed differences between the antitumor effects of the cytotoxic analog and its cytotoxic radical alone, doxorubicin (DOX), on the expression of cancer-related genes by PCR arrays. LH-RH receptors were expressed in two randomly selected surgically removed human pancreatic cancer samples and in all three cancer lines. Cytotoxic LH-RH analogs powerfully inhibited growth of all three tumor lines in nude mice; AN-152 was significantly stronger than DOX on Panc-1 and CFPAC-1 cancers. PCR array showed that cytotoxic LH-RH analog AN-152 affected the expression of genes associated with cellular migration, invasion, metastasis and angiogenesis more favorably than DOX, however the changes in gene expression varied considerably among the three cancer lines. Cytotoxic LH-RH analog, AEZS-108, may be a useful agent for the treatment of LH-RH receptor positive advanced pancreatic carcinoma.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban Molekulatudomány
Megjelenés:	Oncotarget (electronic resources). - 4 : 5 (2013), p. 751-760. -
További szerzők:	Schally, Andrew Victor Block, Norman L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nadji, Mehrdad Szalontay Luca Vidaurre, Irving Abi-Chaker, Andrew Rick Ferenc G.
Pályázati támogatás:	K81596 OTKA TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Peptid hormon és növekedési faktor receptorok mint molekuláris célpontok a humán rosszindulatú daganatok diagnosztikájában és terápiájában
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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