8 research outputs found
Target profiling of an antimetastatic RAPTA agent by chemical proteomics: relevance to the mode of action.
The clinical development of anticancer metallodrugs is often hindered by the elusive nature of their molecular targets. To identify the molecular targets of an antimetastatic ruthenium organometallic complex based on 1,3,5-triaza-7-phosphaadamantane (RAPTA), we employed a chemical proteomic approach. The approach combines the design of an affinity probe featuring the pharmacophore with mass-spectrometry-based analysis of interacting proteins found in cancer cell lysates. The comparison of data sets obtained for cell lysates from cancer cells before and after treatment with a competitive binder suggests that RAPTA interacts with a number of cancer-related proteins, which may be responsible for the antiangiogenic and antimetastatic activity of RAPTA complexes. Notably, the proteins identified include the cytokines midkine, pleiotrophin and fibroblast growth factor-binding protein 3. We also detected guanine nucleotide-binding protein-like 3 and FAM32A, which is in line with the hypothesis that the antiproliferative activity of RAPTA compounds is due to induction of a G2/M arrest and histone proteins identified earlier as potential targets
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Doping liquid argon with xenon in ProtoDUNE Single-Phase: effects on scintillation light
Abstract
Doping of liquid argon TPCs (LArTPCs) with a small
concentration of xenon is a technique for light-shifting and
facilitates the detection of the liquid argon scintillation
light. In this paper, we present the results of the first doping
test ever performed in a kiloton-scale LArTPC. From February to May
2020, we carried out this special run in the single-phase DUNE Far
Detector prototype (ProtoDUNE-SP) at CERN, featuring 720 t of total
liquid argon mass with 410 t of fiducial mass. A 5.4 ppm nitrogen
contamination was present during the xenon doping campaign. The goal
of the run was to measure the light and charge response of the
detector to the addition of xenon, up to a concentration of
18.8 ppm. The main purpose was to test the possibility for
reduction of non-uniformities in light collection, caused by
deployment of photon detectors only within the anode planes. Light
collection was analysed as a function of the xenon concentration, by
using the pre-existing photon detection system (PDS) of ProtoDUNE-SP
and an additional smaller set-up installed specifically for this
run. In this paper we first summarize our current understanding of
the argon-xenon energy transfer process and the impact of the
presence of nitrogen in argon with and without xenon dopant. We then
describe the key elements of ProtoDUNE-SP and the injection method
deployed. Two dedicated photon detectors were able to collect the
light produced by xenon and the total light. The ratio of these
components was measured to be about 0.65 as 18.8 ppm of xenon were
injected. We performed studies of the collection efficiency as a
function of the distance between tracks and light detectors,
demonstrating enhanced uniformity of response for the anode-mounted
PDS. We also show that xenon doping can substantially recover light
losses due to contamination of the liquid argon by nitrogen.</jats:p