Gene expression profiling in primary ovarian serous...

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/68 (2006.01) A61K 38/16 (2006.01) A61K 39/395 (2006.01) A61P 35/00 (2006.01) C12Q 1/00 (2006.01) C12Q 1/04 (2006.01) C40B 30/00 (2006.01) C40B 30/04 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2528606

Gene expression profiling and hierarchial clustering analysis readily distinguish normal ovarian epithelial cells from primary ovarian serous papillary carcinomas. Laminin, tumor-associated calcium signal transducer 1 and 2 (TROP~1/Ep-CAM; TROP-2), claudin 3, claudin 4, ladinin 1, S100A2, SERPIN2 (PAI-2), CD24, lipocalin 2, osteopontin, kallikrein 6 (protease M), kallikrein 10, matriptase and stratifin were found among the most highly overexpressed genes in ovarian serous papillary carcinomas, whereas transforming growth factor beta receptor III, platelet-derived growth factor receptor alpha, SEMACAP3, ras homolog gene family, member I (ARHI), thrombospondin 2 and disabled-2/differentially expressed in ovarian carcinoma 2 (Dab2/DOC2) were significantly down-regulated. Therapeutic strategy targeting TROP-1/Ep-CAM by monoclonal chimeric/humanized antibodies may be beneficial in patients harboring chemotherapy-resistant ovarian serous papillary carcinomas.

Selon cette invention, l'établissement du profil de l'expression génique et l'analyse de classification hiérarchique permettent de distinguer immédiatement des cellules épithéliales ovariennes normales de carcinomes papillaires séreux ovariens primaires. La laminine, le transducteur 1 et 2 de signaux calciques associé aux tumeurs (TROP-1/Ep-CAM ; TROP-2), la claudine 3, la claudine 4, la ladinine 1, S100A2, SERPIN2 (PAI-2), CD24, la lipocaline 2, l'ostéopontine, la kallicréine 6 (protéase M), la kallicréine 10, la matriptase et la stratifine figurent parmi les gènes les plus hautement surexprimés dans les carcinomes papillaires séreux ovariens, tandis que le récepteur III du facteur de croissance transformant bêta, le récepteur alpha du facteur de croissance dérivé des plaquettes, SEMACAP3, la famille génique homologue de ras, le membre I (ARHI), la thrombospondine 2 et un gène 2-déficient/différentiellement exprimé dans un carcinome ovarien 2 (Dab-2/DOC2) sont régulés négativement. Une stratégie thérapeutique ciblant TROP-1/Ep-CAM au moyen d'anticorps chimères/humanisés monoclonaux peut être bénéfique chez des patients souffrant de carcinomes papillaires séreux ovariens résistants à la chimiothérapie.

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