0000000000343610
AUTHOR
Olga A. Fedorova
Novel isatin-derived molecules activate p53 via interference with Mdm2 to promote apoptosis
International audience; The p53 protein is a key tumor suppressor in mammals. In response to various forms of genotoxic stress p53 stimulates expression of genes whose products induce cell cycle arrest and/or apoptosis. An E3-ubiquitin ligase, Mdm2 (mouse-double-minute 2) and its human ortholog Hdm2, physically interact with the amino-terminus of p53 to mediate its ubiquitin-mediated degradation via the proteasome. Thus, pharmacological inhibition of the p53-Mdm2 interaction leads to overall stabilization of p53 and stimulation of its anti-tumorigenic activity. In this study we characterize the biological effects of a novel class of non-genotoxic isatin Schiff and Mannich base derivatives (…
Nanohybrid for Photodynamic Therapy and Fluorescence Imaging Tracking without Therapy
Theranostic upconversion nanoparticles (UCNPs) are ideal candidates for personalized medicine. We present a smart, easy-to-prepare nanohybrid (NH) suitable for NIR-theragnosis and imaging tracking without triggering therapy simultaneously. The photophysical features of each component have been carefully selected in order to maximize the capabilities for theragnosis, in particular, the upconversion emission and the photosensitizer absorption. In addition, NH presents a fluorescent marker with one-photon absorption in the green and two-photon absorption cross-section at NIR wavelengths where the UCNP does not absorb, thus enabling innocuous tracking. Thus, the NH consists of NaYF4:Yb, Er, Tm …
Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy
AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…