Identification of Anti-Malarial Compounds as Novel Antagonists to Chemokine Receptor CXCR4 in Pancreatic Cancer Cells

Despite recent advances in targeted therapies, patients with pancreatic adenocarcinoma continue to have poor survival highlighting the urgency to identify novel therapeutic targets. Our previous investigations have implicated chemokine receptor CXCR4 and its selective ligand CXCL12 in the pathogenesis and progression of pancreatic intraepithelial neoplasia and invasive pancreatic cancer; hence, CXCR4 is a promising target for suppression of pancreatic cancer growth. Here, we combined in silico structural modeling of CXCR4 to screen for candidate anti-CXCR4 compounds with in vitro cell line assays and identified NSC56612 from the National Cancer Institute's (NCI) Open Chemical Repository Collection as an inhibitor of activated CXCR4. Next, we identified that NSC56612 is structurally similar to the established anti-malarial drugs chloroquine and hydroxychloroquine. We evaluated these compounds in pancreatic cancer cells in vitro and observed specific antagonism of CXCR4-mediated signaling and cell proliferation. Recent in vivo therapeutic applications of chloroquine in pancreatic cancer mouse models have demonstrated decreased tumor growth and improved survival. Our results thus provide a molecular target and basis for further evaluation of chloroquine and hydroxychloroquine in pancreatic cancer. Historically safe in humans, chloroquine and hydroxychloroquine appear to be promising agents to safely and effectively target CXCR4 in patients with pancreatic cancer

A twin-screw extruder for oil extraction: I. Direct expression of oleic sunflower seeds

13 ref.International audienc

Response of Correlated Double Sampling CMOS Imager Circuit to Random Telegraph Signal Noise

International audienc

Low frequency Noise Measurements as an investigation tool of pixel flickering in cooled Hg0,7Cd0,3Te focal plane arrays

International audienceWe report on electrical noise measurements on both Hg0.7Cd0.3Te test patterns and hybrid 320 x 256 focal plane array in order to explain the low-frequency pixel flickering physical origin. Dark and under infrared Illumination test patterns characterization highlights that the detector chip is not responsible for the flickering phenomenon. Taking into account the silicon readout chip influence when the full infrared complementary metal-oxyd semiconductor (IRCMOS) infrared detector is investigated, the indium bump based interconnecting system is finally pointed out as a potential excess noise source

RGK GTPase-dependent CaV2.1 Ca2+ channel inhibition is independent of CaVbeta-subunit-induced current potentiation.

International audienceRGK (Rad-Gem-Rem) GTPases have been described as potent negative regulators of the Ca(2+) influx via high-threshold voltage-activated Ca(2+) channels. Recent work, mostly performed on Ca(V)1.2 Ca(2+) channels, has highlighted the crucial role played by the channel auxiliary Ca(V)beta subunits and identified several GTPase and beta-subunit protein domains involved in this regulation. We now extend these conclusions by producing the first complete characterization of the effects of Gem, Rem, and Rem2 on the neuronal Ca(V)2.1 Ca(2+) channels expressed with Ca(V)beta(1) or Ca(V)beta(2) subunits. Current inhibition is limited to a decrease in amplitude with no modification in the voltage dependence or kinetics of the current. We demonstrate that this inhibition can occur for Ca(V)beta constructs with impaired capacity to induce current potentiation, but that it is lost for Ca(V)beta constructs deleted for their beta-interaction domain. The RGK C-terminal last approximately 80 amino acids are sufficient to allow potent current inhibition and in vivo beta-subunit/Gem interaction. Interestingly, although Gem and Gem carboxy-terminus induce a completely different pattern of beta-subunit cellular localization, they both potently inhibit Ca(V)2.1 channels. These data therefore set the status of neuronal Ca(V)2.1 Ca(2+) channel inhibition by RGK GTPases, emphasizing the role of short amino acid sequences of both proteins in beta-subunit binding and channel inhibition and revealing a new mechanism for channel inhibition

Production de viandes de Porcs mâles entiers ou castrés : efficacité alimentaire et composition corporelle chez les races hypermusclées

International audienc

Dye-Sensitized Nanostructured Crystalline Mesoporous Tin-doped Indium Oxide Films with Tunable Thickness for Photoelectrochemical Applications.

International audienceA simple route towards nanostructured mesoporous Indium-Tin Oxide (templated nano-ITO) electrodes exhibiting both high conductivities and optimized bicontinuous pore-solid network is reported. The ITO films are first produced as an X-ray-amorphous, high surface area material, by adapting recently established template-directed sol-gel methods using Sn(IV) and In(III) salts. Carefully controlled temperature/atmosphere treatments convert the as-synthesized ITO films into nano-crystalline coatings with the cubic bixbyite structure. Specially, a multi-layered synthesis was successfully undertaken for tuning the film thickness. In order to evaluate the performances of templated nano-ITO as an electrode substrate for photoelectrochemical applications, photoelectrodes were prepared by covalent grafting of a redox-active dye, the complex [Ru(bpy)2(4,4'-(CH2PO3H2)2-bpy)]Cl2 1 (bpy=bipyridine). Surface coverage was shown to increase with the film thickness, from 0.7 × 10(-9) mol.cm(-2) (one layer, 45 nm) to 3.5 × 10(-9) mol.cm(-2) (ten layers, 470 nm), the latter value being ~ 100 times larger than that for commercially available planar ITO. In the presence of an electron mediator, photocurrents up to 50 μA.cm(-2) have been measured under visible light irradiation, demonstrating the potential of this new templated nano-ITO preparation for the construction of efficient photoelectrochemical devices

Microbial Dynamics and Control in Shale Gas Production

Microorganisms can cause detrimental effects in shale gas production, such as reservoir souring, plugging, equipment corrosion, and a decrease in hydrocarbon production volume and quality, thus representing a multi-billion-dollar problem. Prefracturing fluids, drilling mud, and impoundment water likely introduce deleterious microorganisms into shale gas reservoirs. Conditions within the reservoir generally select for halotolerant anaerobic microorganisms. Microbial abundance and diversity in flowback waters decrease shortly after hydraulic fracturing, with Clostridia, a class that includes spore-forming microorganisms, becoming dominant. The rapid microbial community successions observed suggest biocides are not fully effective, and more targeted treatment strategies are needed. At the impoundment level, microbial control strategies should consider biocide rotation, seasonal loading adjustments, and biocide pulse dosing. In shale plays where souring is common, stable ³⁴S/³²S isotope analysis to identify abiotic H₂S is recommended to evaluate the merits of biocide application in treating reservoir souring. Overall, an improved understanding of the microbial ecology of shale gas reservoirs is needed to optimize microbial control, maximize well productivity, and reduce environmental and financial burdens associated with the <i>ad hoc</i> misuse and overuse of biocides