Search results for "Modulator"
showing 10 items of 210 documents
Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymeri…
2008
Molecules that target microtubules have an important role in the treatment of cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
Integrated photonic routers driven by surface acoustic waves
2016
Durante la segunda mitad del siglo XX se produjo un desarrollo excepcional de la capacidad de transmitir y procesar información electrónicamente. Esto fue debido en parte a la capacidad de integrar en un único substrato una gran cantidad de transistores, que son las unidades fundamentales de procesamiento de datos. Este comportamiento quedó resumido en la ley de Moore, que predecía que el número de transistores integrados se duplicaría cada 24 meses. Esta tendencia, que se ha mantenido hasta la actualidad con transistores de tamaño nanométrico, no puede continuar indefinidamente. Uno de los problemas fundamentales reside en la capacidad limitada para disipar el calor que generan los disposi…
Technical Advance:Soluble OX40 molecule mimics regulatory T cell modulatory activity on Fc{varepsilon}RI-dependent mast cell degranulation.
2011
Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in pa…
A differential role of CREB phosphorylation in cAMP-inducible gene expression in the rat pineal
2000
In the rat pineal gland cAMP mediates nocturnal induction of the enzyme arylalkylamine N-acetyltransferase (AA-NAT) as well as of transcription factors such as inducible cAMP early repressor (ICER), Fos-related antigen-2 (Fra-2) and JunB. Cyclic AMP stimulates the phosphorylation of the DNA binding protein cAMP response element binding protein (CREB). While cAMP-induced CREB phosphorylation appears to be a prerequisite for AA-NAT and ICER gene expression, it is not known whether CREB phosphorylation accounts for the full cAMP response of the two genes. Furthermore, the significance of CREB phosphorylation in cAMP-activated Fra-2 and JunB transcription is unknown. In the present in vitro stu…
Synthesis and biological evaluation of 2-(3 ',4 ',5 '-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors
2006
2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para-position of the 5-phenyl group showed antiproliferative activity in the order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of apoptosis.
Targeting cancer stem cells and the tumor microenvironment
2015
Compelling evidence indicates that the survival and behavior of cancer stem cells (CSCs) are positively regulated by specific stimuli received from the tumor microenvironment, which dictates the maintenance of stemness, invasiveness, and protection against drug-induced apoptotic signals. CSCs are per se endowed with multiple treatment resistance capabilities, thus the eradication of CSC pools offers a precious strategy in achieving a long-term cancer remission. Numerous therapies, aimed at eradicating CSCs, have been elaborated such as: (i) selective targeting of CSCs, (ii) modulating their stemness and (iii) influencing the microenvironment. In this context, markers commonly exploited to i…
Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.
2011
International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…
Rituximab in refractory Vogt-Koyanagi-Harada disease.
2011
Introduction Vogt–Koyanagi–Harada (VKH) prognosis depends on early recognition and treatment; chronic disease may be developed when either delayed or inadequate treatment is performed, whereas other cases despite correct treatment are refractory to different drugs and also become chronic. We report a case of refractory VKH controlled with rituximab treatment. Case report A 41-year-old female with painful visual loss and headache was examined. (VA 0.4 in RE and hand movements (HM) in LE). Retinal examination demonstrated multiple serous retinal detachments in both eyes. High-dose oral steroids were started, followed by progressive tapering of prednisone. New acute anterior and posterior rela…
Dynamic wavefront sensing and correction with low-cost twisted nematic spatial light modulators
2010
Off-the-shelf spatial light modulators (SLMs), like twisted nematic liquid crystal displays (TNLCDs) used in projection systems, show some interesting features such as high spatial resolution, easy handling, wide availability, and low cost. We describe a compact adaptive optical system using just one TNLCD to measure and compensate optical aberrations. The current system operates at a frame rate of the order of 10 Hz with a four-level codification scheme. Wavefront estimation is performed through conventional Hartmann–Shack sensing architecture. The system has proved to work properly with a maximum rms aberration of 0. 76 μm and wavefront gradient of 50 rad/mm at a wavelength of 514 nm. The…
Phase-shifting Gabor holography.
2009
We present a modified Gabor-like setup able to recover the complex amplitude distribution of the object wavefront from a set of inline recorded holograms. The proposed configuration is characterized by the insertion of a condenser lens and a spatial light modulator (SLM) into the classical Gabor configuration. The phase shift is introduced by the SLM that modulates the central spot (dc term) in an intermediate plane, without an additional reference beam. Experimental results validate the proposed method and produce superior results to the Gabor method.