References of "Noël, Agnes"
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See detailCombination treatment of cancer
PAYE, Alexandra ULg; Sounni, Nor Eddine ULg; NOEL, Agnès

Patent (2015)

The present invention provides MT4-MMP inhibitor and EGFR inhibitor for use in the treatment of cancer, wherein said MT4-MMP inhibitor and EGFR inhibitor are different from each other. MT4-MMP (MMP-17) is ... [more ▼]

The present invention provides MT4-MMP inhibitor and EGFR inhibitor for use in the treatment of cancer, wherein said MT4-MMP inhibitor and EGFR inhibitor are different from each other. MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol (GPI) anchored MMP produced by cancer cells that promotes tumor vascularization and metastases. The present invention found that MT4-MMP expression promotes cancer cell proliferation. These effects involve retinoblastoma protein (Rb) inactivation, cyclin dependent kinase CDK4 activation and Epidermal Growth Factor Receptor (EGFR) signaling. Co-immuno-precipitations indicate the existence of protein complexes harboring MT4-MMP and EGFR. The present invention further found a novel mechanism of MT4-MMP action through an outside-in signaling involving EGFR. An unexpected crosstalk between an MMP and EGFR was identified and recognized as a key driver of cancer cell biology. [less ▲]

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See detailThe timing of surgery after neoadjuvant radiotherapy influences tumor dissemination in a preclinical model
Leroi, Natacha ULg; Sounni, Nor Eddine ULg; Van Overmeire, Eva et al

in Oncotarget (2015)

Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving local tumor control and patient overall survival. The neoRT schedule and the timing of the surgical treatment (ST) are ... [more ▼]

Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving local tumor control and patient overall survival. The neoRT schedule and the timing of the surgical treatment (ST) are empirically based and influenced by the clinician’s experience. The current study examines how the sequencing of neoRT and ST affects metastatic dissemination. In a breast carcinoma model, tumors were exposed to different neoRT schedules (2x5Gy or 5x2Gy) followed by surgery at day 4 or 11 post- RT. The impact on the tumor microenvironment and lung metastases was evaluated through immunohistochemical and flow cytometry analyses. After 2x5Gy, early ST (at day 4 post-RT) led to increased size and number of lung metastases as compared to ST performed at day 11. Inversely, after 5x2Gy neoRT, early ST protected the mice against lung metastases. This intriguing relationship between tumor aggressiveness and ST timing could not be explained by differences in classical parameters studied such as hypoxia, vessel density and matrix remodeling. The study of tumor-related inflammation and immunity reveals an increased circulating NK cell percentage following neoRT as compared to non irradiated mice. Then, radiation treatment and surgery were applied to tumor-bearing NOD/SCID mice. In the absence of NK cells, neoRT appears to increase lung metastatic dissemination as compared to non irradiated tumor-bearing mice. Altogether our data demonstrate that the neoRT schedule and the ST timing affect metastasis formation in a pre-clinical model and points out the potential role of NK cells. These findings highlight the importance to cautiously tailor the optimal window for ST following RT. [less ▲]

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