Next-generation Trop-2-targeted therapy against advanced cancers is hampered by expression of Trop-2 in normal tissues. We discovered that Trop-2 undergoes proteolytic activation by ADAM10 in cancer cells, leading to the exposure of a previously inaccessible protein groove flanked by two N-glycosylation sites. We designed a recognition strategy for this region, to drive selective cancer vulnerability in patients.
View Article and Find Full Text PDFWe recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models.
View Article and Find Full Text PDFBackground: GATA binding protein 3 () expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up.
Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and , and scored.
Background: Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated.
Aim: To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature.