Relación entre el valor del ratio elastográfico y la clasificación citológica de Bethesda en la patología tiroidea

ResumenObjetivoPresentar nuestra experiencia en la categorización de la patología tiroidea, a través de la utilización de parámetros ecográficos de malignidad y elastografía con medición del ratio de la deformación tisular, y la correlación de los hallazgos obtenidos con la clasificación citológica de Bethesda.Materiales y métodosSe llevó a cabo un estudio prospectivo y observacional, entre septiembre de 2012 y abril de 2013, que incluyó 137 nódulos tiroideos. Se excluyeron 10 casos Bethesda III-IV. Se realizó ecografía, power Doppler, visualización de micropartículas (Micropure) y elastografía con medición del ratio elastográfico, así como también punción aspirativa con aguja fina guiada por ecografía (con el citólogo presente), utilizando la clasificación Bethesda. Los estudios fueron hechos por el mismo operador con un ecógrafo Toshiba Aplio 400 y los datos estadísticos se evaluaron con el programa IBM SPSS Statistics 20.ResultadosSe estudiaron 127 nódulos en pacientes con una edad promedio de 59±16 años. El 82% de los casos ocurrió en mujeres. Ciento veinte nódulos (94%) fueron clasificados como Bethesda II. La media elastográfica para Bethesda I-II fue de 1,94±2,12 vs. 7,07±5,46 para V-VI (p: 0,048). El punto de corte elastográfico ≤ 2 (87 de 127) presentó una sensibilidad del 85,7% y una especificidad del 81,7% para predecir Bethesda asociada a patología benigna, con un valor predictivo negativo (VPN) del 99% y un valor predictivo positivo del 15%.ConclusionesEl ratio elastográfico permitió descartar la patología tiroidea maligna con valores ≤ 2 y un VPN del 99%, mejorando la selección de los pacientes a punzar. El incremento del ratio elastográfico se asoció a una mayor probabilidad de patología maligna, aunque no se pudo establecer un valor de corte debido al bajo número de casos con Bethesda V-VI.AbstractObjectivesWe present our experience in the categorization of thyroid pathology using the sonographic parameters of malignancy and elastography with measurement elastography strain ratio, to evaluate the relationship between the results found and the Bethesda classification.Materials and methodsProspective observational study, included 137 thyroid nodules studied between September 2012- April 2013. We excluded 10 cases with Bethesda categories III-IV. Ultrasonography, Doppler, Micropure, elastogrphy strain ratio between the lesion and the normal tissue, fine needle aspiration cytology (FNAC),were the diagnosis methods used. The pathologist was always present and the cytological classi fication of Bethesda was used. All study was made by the same physician used Toshiba Aplio 400 ultrasound unit. Results were analyzed with IBM SPSS Statistics 20.ResultsWe studied 127 nodules in patients 59±16 years old, 82% were female; 120 were Bethesda II (94%). The average strain ratio for nodules Bethesda I-II was 1.94±2.12 vs. 7.07±5.46 for those nodules Bethesda V-VI (p:0,048). This means that an elastography strain ratio ≤ 2 (87 of 127 nodules) has a sensibility of 85.7% and a specificity of 81.7% of predicting Bethesda associated with benign pathology with a negative predictive value (NPV) of 99% and a positive predictive value of 15%.ConclusionThe elastography strain ratio allowed to discard malignant nodules with strain ratio ≤ 2 with a NPV of 99% improves the selection of patients for FNAC. The increment in the elastography strain ratio was associated to a higher possibility of malignant thyroid pathology, being unable to determine a limit value due to the low amount of cases with nodules Bethesda V-VI

Real-space mapping of tailored sheet and edge plasmons in graphene nanoresonators

Plasmons in graphene nanoresonators have many potential applications in photonics and optoelectronics, including room-temperature infrared and terahertz photodetectors, sensors, reflect arrays or modulators1, 2, 3, 4, 5, 6, 7. The development of efficient devices will critically depend on precise knowledge and control of the plasmonic modes. Here, we use near-field microscopy8, 9, 10, 11 between λ0 = 10–12 μm to excite and image plasmons in tailored disk and rectangular graphene nanoresonators, and observe a rich variety of coexisting Fabry–Perot modes. Disentangling them by a theoretical analysis allows the identification of sheet and edge plasmons, the latter exhibiting mode volumes as small as 10−8λ03. By measuring the dispersion of the edge plasmons we corroborate their superior confinement compared with sheet plasmons, which among others could be applied for efficient 1D coupling of quantum emitters12. Our understanding of graphene plasmon images is a key to unprecedented in-depth analysis and verification of plasmonic functionalities in future flatland technologies.Peer ReviewedPostprint (author's final draft

SEMA6C: a novel adhesion-independent FAK and YAP activator, required for cancer cell viability and growth

Transmembrane semaphorins are signaling molecules, controlling axonal wiring and embryo development, which are increasingly implicated in human diseases. Semaphorin 6C (Sema6C) is a poorly understood family member and its functional role is still unclear. Upon targeting Sema6C expression in a range of cancer cells, we observed dramatic growth suppression, decreased ERK phosphorylation, upregulation of cell cycle inhibitor proteins p21, p27 and p53, and the onset of cell senescence, associated with activation of autophagy. These data are consistent with a fundamental requirement for Sema6C to support viability and growth in cancer cells. Mechanistically, we unveiled a novel signaling pathway elicited by Sema6C, and dependent on its intracellular domain, mediated by tyrosine kinases c-Abl and Focal Adhesion Kinase (FAK). Sema6C was found in complex with c-Abl, and induced its phosphorylation, which in turn led to FAK activation, independent of cell–matrix adhesion. Sema6C-induced FAK activity was furthermore responsible for increased nuclear localization of YAP transcriptional regulator. Moreover, Sema6C conferred YAP signaling-dependent long-term cancer cell survival upon nutrient deprivation. In conclusion, our findings demonstrate that Sema6C elicits a cancer promoting-signaling pathway sustaining cell viability and self-renewal, independent of growth factors and nutrients availability

Frequency combs induced by phase turbulence

Wave instability—the process that gives rise to turbulence in hydrodynamics1—represents the mechanism by which a small disturbance in a wave grows in amplitude owing to nonlinear interactions. In photonics, wave instabilities result in modulated light waveforms that can become periodic in the presence of coherent locking mechanisms. These periodic optical waveforms are known as optical frequency combs2–4. In ring microresonator combs5,6, an injected monochromatic wave becomes destabilized by the interplay between the resonator dispersion and the Kerr nonlinearity of the constituent crystal. By contrast, in ring lasers instabilities are considered to occur only under extreme pumping conditions7,8. Here we show that, despite this notion, semiconductor ring lasers with ultrafast gain recovery9,10 can enter frequency comb regimes at low pumping levels owing to phase turbulence11—an instability known to occur in hydrodynamics, superconductors and Bose–Einstein condensates. This instability arises from the phase–amplitude coupling of the laser field provided by linewidth enhancement12, which produces the needed interplay of dispersive and nonlinear effects. We formulate the instability condition in the framework of the Ginzburg–Landau formalism11. The localized structures that we observe share several properties with dissipative Kerr solitons, providing a first step towards connecting semiconductor ring lasers and microresonator frequency combs13

Magnetoplasmonic design rules for active magneto-optics

Light polarization rotators and non-reciprocal optical isolators are essential building blocks in photonics technology. These macroscopic passive devices are commonly based on magneto-optical Faraday and Kerr polarization rotation. Magnetoplasmonics - the combination of magnetism and plasmonics - is a promising route to bring these devices to the nanoscale. We introduce design rules for highly tunable active magnetoplasmonic elements in which we can tailor the amplitude and sign of the Kerr response over a broad spectral range

Retinoic acid synergizes with the unfolded protein response and oxidative stress to induce cell death in FLT3-ITD+ AML.

Acute myeloid leukemia (AML) is often characterized by the expression of fusion or mutant proteins that cause impaired differentiation and enhanced proliferation and survival. The presence of mutant proteins prone to misfolding can render the cells sensitive to endoplasmic reticulum (ER) stress and oxidative stress that could otherwise be overcome. Here, we show that the triple combination of the differentiating agent retinoic acid (RA), the ER stress-inducing drug tunicamycin (Tm), and arsenic trioxide (ATO), able to generate oxidative stress, leads to the death of AML cell lines expressing fusion proteins involving the gene MLL and the internal tandem duplication (ITD) in the FLT3 tyrosine kinase receptor. Importantly, the combination of RA, Tm, and ATO decreased the colony-forming capacity of primary leukemic blasts bearing the FLT-ITD mutation without affecting healthy hematopoietic progenitor cells. We demonstrate in cell lines that combination of these drugs generates ER and oxidative stresses and impairs maturation and causes accumulation of FLT3 protein in the ER. Our data provide a proof of concept that low amounts of drugs that generate ER and oxidative stresses combined with RA could be an effective targeted therapy to hit AML cells characterized by MLL fusion proteins and FLT3-ITD mutation

Semaphorin 3A Suppresses Tumor Growth and Metastasis in Mice Melanoma Model

<div><h3>Background</h3><p>Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A) acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation.</p> <h3>Methodology/Principal Findings</h3><p>In this study, using multiple <em>in vitro</em> and <em>in vivo</em> approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor <em>in vitro</em> and <em>in vivo</em> mice (C57BL/6) models. Mouse melanoma (B16F10) cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of <em>in vivo</em> tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents.</p> <h3>Conclusions</h3><p>Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.</p> </div

A peptide corresponding to the neuropilin-1-binding site on VEGF165 induces apoptosis of neuropilin-1-expressing breast tumour cells

There is increasing evidence that vascular endothelial growth factor (VEGF) has autocrine as well as paracrine functions in tumour biology. Vascular endothelial growth factor-mediated cell survival signalling occurs via the classical tyrosine kinase receptors Flt-1, KDR/Flk-1 and the more novel neuropilin (NP) receptors, NP-1 and NP-2. A 24-mer peptide, which binds to neuropilin-1, induced apoptosis of murine and human breast carcinoma cells, whereas a peptide directed against KDR had no effect. Both anti-NP1 and anti-KDR peptides induced endothelial cell apoptosis. Confocal microscopy using 5-(6)-carboxyfluorescein-labelled peptides showed that anti-NP1 bound to both tumour and endothelial cells, whereas anti-KDR bound endothelial cells only. This study demonstrates that NP-1 plays an essential role in autocrine antiapoptotic signalling by VEGF in tumour cells and that NP1-blockade induces tumour cell and endothelial cell apoptosis. Specific peptides can therefore be used to target both autocrine (tumour cells) and paracrine (endothelial cells) signalling by VEGF

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.Fil: Quintá, Héctor Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Pasquini, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentin