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001-es BibID:	BIBFORM040824
Első szerző:	Seitz, Stephan
Cím:	Targeting triple-negative breast cancer through the somatostatin receptor with the new cytotoxic somatostatin analogue AN-162 [AEZS-124] / Seitz Stephan, Buchholz Stefan, Schally Andrew V., Jayakumar Arumugam R., Weber Florian, Papadia Andrea, Rick Ferenc G., Szalontay Luca, Treszl Andrea, Köster Frank, Ortmann Olaf, Hohla Florian
Dátum:	2013
ISSN:	0959-4973
Megjegyzések:	Previously, we have shown that the targeted cytotoxic somatostatin (sst) analogue AN-162 [AZSE-124] inhibits the growth of MDA-MB-231 human breast cancers xenografted into nude mice. In this study, we examined the trafficking of AN-162 into the cell, the expression of the somatostatin receptors (sstr) in specimens of human triple-negative breast cancers (TNBC), and the effect of AN-162 on HCC 1806 human TNBC xenografts. The expression of sstr in TNBC tumor samples was investigated by immunohistochemical staining. The expression of sstr in HCC 1806 was evaluated by reverse transcription PCR. Internalization studies with I-labeled AN-162 were carried out and the autofluorescence sign of doxorubicin moiety in the cell nucleus after incubation with AN-162 was measured using a fluorescence assay. The effects of AN-162 on the growth of HCC 1806 xenografted into nude mice were studied. A fluorescence microscopy cytotoxicity assay in vitro to detect cell death after treatment with AN-162 was also carried out. About 28% of TNBC tumor specimens showed a positive staining for sstr subtype 2a. HCC 1806 expresses all five subtypes of sstr. In the fluorescence cytotoxicity assay, dead HCC 1806 cells were found 24 h after incubation with AN-162. The growth of HCC 1806 tumors in nude mice was significantly inhibited by treatment with AN-162. AN-162 was internalized into the HCC 1806 cells and doxorubicin moiety was detected in the cell nuclei. This study is the first to show that the trafficking of the cytotoxic sst analogue AN-162 into the cell is mediated by sstr. Our work shows that the growth of xenografted HCC 1806 TNBCs can be effectively inhibited in vivo with AN-162. This investigation provides information on the mechanism of action and efficacy of this new targeted cytotoxic sst analogue and identifies in this relation the sstr as a favorable therapeutic target in TNBC.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Anti-Cancer Drugs. - 24 : 2 (2013), p. 150-157. -
További szerzők:	Buchholz, Stefan Schally, Andrew Victor Jayakumar, Arumugam R. Weber, Florian Papadia, Andrea Rick Ferenc G. Szalontay Luca Treszl Andrea (1974-) (molekuláris biológus) Köster, Frank Ortmann, Olaf Hohla, Florian
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