Tuesday, January 05, 2010
abstract/full text: Gene silencing of glypican-3 in clear cell carcinoma of the ovary renders it more sensitive to the apoptotic agent paclitaxel
"Clear cell carcinoma has been classified as a subgroup of EOC and reported to be an interesting histologic type with unique clinical features. CCC showed a poorer prognosis compared to serous adenocarcinoma because it tended to be resistant to antineoplastic agents, including paclitaxel.
CCC comprises more than 15% of EOC cases in Japan, although it represents 8–10% of all EOC cases in the USA. Therefore, it is important to establish new treatment strategies to improve the prognosis of CCC patients.
GPC3 regulates cell growth either positively or negatively depending on the cell type. Genetic and functional studies showed that glypicans regulate the signaling activity of various morphogens, including Wnts, Hedgehogs, bone morphogenic proteins, and fibroblast growth factors. Previous studies showed that GPC3 was overexpressed in Wilms' tumor, hepatocellular carcinoma, and hepatoblastoma. In ovarian carcinoma, GPC3 was overexpressed in yolk sac tumor and CCC.(15–17) However, GPC3 function in CCC was unclear. Furthermore, we investigated the role of this molecule in the sensitivity of CCC to paclitaxel, which is a key drug for ovarian cancer, using shRNA targeting GPC3.
Taken together, our data could support the use of GPC3-targeted therapies for CCC patients. We suggest that therapy targeting to GPC3 may be a novel treatment strategy that could potentially help to prevent the appearance, progression, and/or recurrence of CCC."
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