The effect of Kamchatka crab hepatopancreas containing three collagenolytic isoenzymes Collagenase KK and proteinases of
Streptomyces lavendulae
on metabolic activity and cell death were carried out ...on
in vitro
models. It was shown that changes in the protein structure under the influence of Collagenase KK occurred earlier than under the effect of bacterial proteinases. At the same time, activity of Collagenase KK was significantly higher than that of bacterial proteinases (
p
<0.01). Both preparations had a pronounced time- and dose-dependent effects on metabolic activity of cells. Collagenase KK had low cytotoxic effect, and cells mainly died by apoptosis. Thus, hepatopancreas collagenase has a high activity and proapoptotic effect on cells and can be used in low concentrations for enzymatic disaggregation of tissues.
A series of silica mesoporous molecular sieves SBA-15 with a 7.7 ± 0.8 nm pore diameter, the surface of which is hydrophobized with methylsilyl groups, and polymethylsiloxane derivatives with a 1.6 ± ...0.8 nm pore diameter were obtained. These sieves are characterized by X-ray phase analysis, adsorption of nitrogen at 77 K and water at 293 K, as well as IR spectroscopy. It is established that there is a significant resistance to water intrusion (absorption) only in the case of substances characterized by the nitrogen adsorption potential value ∆μ
0
≤ 6.4 kJ/mol. The studied systems can be used as “molecular springs” in shock load damping devices due to their functional properties.
The strength of the acid sites in isostructural hierarchical porous zeolites increases in the order BSiO < GaSiO < AlSiO, and the concentration in the structural types increases in the order MTW < ...BEA < MOR. Zeolite materials with BEA and MOR topology, which consist of nanocrystals with ultrathin-layer morphology, are characterized by a marked decrease of the adsorption potential compared with isostructural materials with nanorods or nanosphere morphology due to a 1.5-fold decrease in the isosteric heats of adsorption of triethylamine.
Metastatic cancers commonly activate adaptive chemotherapy resistance, attributed to both microenvironment‐dependent phenotypic plasticity and genetic characteristics of cancer cells. However, the ...contribution of chemotherapy itself to the non‐genetic resistance mechanisms was long neglected. Using high‐grade serous ovarian cancer (HGSC) patient material and cell lines, we describe here an unexpectedly robust cisplatin and carboplatin chemotherapy‐induced ERK1/2‐RSK1/2‐EphA2‐GPRC5A signaling switch associated with cancer cell intrinsic and acquired chemoresistance. Mechanistically, pharmacological inhibition or knockdown of RSK1/2 prevented oncogenic EphA2‐S897 phosphorylation and EphA2‐GPRC5A co‐regulation, thereby facilitating a signaling shift to the canonical tumor‐suppressive tyrosine phosphorylation and consequent downregulation of EphA2. In combination with platinum, RSK inhibitors effectively sensitized even the most platinum‐resistant EphA2high, GPRC5Ahigh cells to the therapy‐induced apoptosis. In HGSC patient tumors, this orphan receptor GPRC5A was expressed exclusively in cancer cells and associated with chemotherapy resistance and poor survival. Our results reveal a kinase signaling pathway uniquely activated by platinum to elicit adaptive resistance. They further identify GPRC5A as a marker for abysmal HGSC outcome and putative vulnerability of the chemo‐resistant cells to RSK1/2‐EphA2‐pS897 pathway inhibition.
Synopsis
Platinum chemotherapy induces RSK1/2‐EphA2‐GPRC5A oncogenic signaling switch associated to intrinsic and acquired resistance. This study identifies GPRC5A as a marker for poor therapy response and vulnerability of the resistant cells to RSK1/2‐EphA2‐pS897 pathway inhibition in ovarian cancer.
The oncogenic switch is mediated by platinum‐activated ERK1/2‐RSK1/2 pathway coupled with co‐localization of EphA2 and the EphA2‐interacting orphan receptor GPRC5A.
RSK inhibition impairs, through EphA2‐pY588 activation and consequent EphA2 downregulation, the platinum‐induced resistance‐associated GPRC5A‐EphA2‐pS897 co‐regulation, thus sensitizing HGSC cell to platinum.
GPRC5A expression is associated with HGSC cell sensitivity to RSKi‐platinum combination treatment ex vivo.
In human HGSC tumors, high GPRC5A levels are correlated with poor treatment response, as well as adverse overall and progression‐free patient survival. Combined EphA2‐GPRC5A expression predict shorter progression‐free survival.
Platinum chemotherapy induces RSK1/2‐EphA2‐GPRC5A oncogenic signaling switch associated to intrinsic and acquired resistance. This study identifies GPRC5A as a marker for poor therapy response and vulnerability of the resistant cells to RSK1/2‐EphA2‐pS897 pathway inhibition in ovarian cancer.
Statistical fluctuations of the magnetization are measured on the nanometer scale. As the experimental monitor we use the characteristic photoluminescence signal of a single electron-hole pair ...confined in one magnetic semiconductor quantum dot, which sensitively depends on the alignment of the magnetic ion spins. Quantitative access to statistical magnetic fluctuations is obtained by analyzing the linewidth broadening of the single dot emission. Our all-optical technique allows us to address a magnetic moment of only approximately equal 100 micro(B) and to resolve statistical changes on the order of a few micro(B).
The MPD detector at the NICA heavy-ion collider at JINR Afanasiev, S.V.; Alfeev, V.S.; Aslanyan, P.Zh ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2011, Letnik:
628, Številka:
1
Journal Article
Recenzirano
The MultiPurpose Detector (MPD) is designed to study heavy-ion collisions at the Nuclotron-based heavy Ion Collider fAcility (NICA) at JINR, Dubna. Its main components located inside a ...superconducting solenoid are a tracking system composed of a silicon microstrip vertex detector followed by a large volume time-projection chamber, a time-of-flight system for particle identification and a barrel electromagnetic calorimeter. A zero degree hadron calorimeter is designed specifically to measure the energy of spectators. In this paper, all parts of the apparatus are described and their tracking and particle identification (PID) parameters are discussed in some detail.
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