Head and Neck Diseases by Alexandros G.Sfakianakis: 11/23/16

Τετάρτη 23 Νοεμβρίου 2016

An Unusual Laryngeal Foreign Body in Adult

The accidental aspiration of a foreign body is a frequent domestic accident among children but a rare occurrence in adults. The laryngeal impaction of a coin is an unusual accident; only a few cases have been reported in the literature. Diagnosis is mostly achieved by clinicoradiological examinations. The authors report an uncommon case of laryngeal impaction of a coin in a 21-year-old patient, presenting with dysphonia without dyspnea or stridor. The extraction was performed by endoscopy.

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An Unusual Laryngeal Foreign Body in Adult

Screening for ALK abnormalities in central nervous system metastases of non-small-cell lung cancer

Abstract

Anaplastic lymphoma kinase (ALK) gene rearrangement was reported in 3-7% of primary non-small-cell lung cancer (NSCLC) and its presence is commonly associated with adenocarcinoma (AD) type and non-smoking history. ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement. Moreover, response to ALK TKIs was observed in central nervous system (CNS) metastatic lesions of NSCLC. However, there are no reports concerning the frequency of ALK rearrangement in CNS metastases. We assessed the frequency of ALK abnormalities in 145 formalin fixed paraffin embedded (FFPE) tissue samples from CNS metastases of NSCLC using immunohistochemical (IHC) automated staining (BenchMark GX, Ventana, USA) and fluorescence in situ hybridization (FISH) technique (Abbot Molecular, USA). The studied group was heterogeneous in terms of histopathology and smoking status. ALK abnormalities were detected in 4.8% (7/145) of CNS metastases. ALK abnormalities were observed in six AD (7.5%; 6/80) and in single patients with adenosuqamous lung carcinoma. Analysis of clinical and demographic factors indicated that expression of abnormal ALK was significantly more frequently observed (p=0.0002; χ²=16.783) in former-smokers. Comparison of IHC and FISH results showed some discrepancies, which were caused by unspecific staining of macrophages and glial/nerve cells, which constitute the background of CNS tissues. Our results indicate high frequency of ALK gene rearrangement in CNS metastatic sites of NSCLC that are in line with prior studies concerning evaluation of the presence of ALK abnormalities in such patients. However, we showed that assessment of ALK by IHC and FISH methods in CNS tissues require additional standardizations. This article is protected by copyright. All rights reserved.

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Lutein and atherosclerosis: Belfast versus Toulouse revisited

Publication date: Available online 23 November 2016
Source:Medical Hypotheses
Author(s): A.N. Howard, D.I. Thurnham
In 1995 we reported that mean plasma lutein concentrations in salaried men and women from Toulouse in Southern France were double those in subjects recruited from general practitioner lists in Belfast, Northern Ireland. At the time incidence of coronary heart disease (CHD) in Southern France was among the lowest in Europe and was much higher in Northern Ireland. Plasma lutein is a biomarker of vegetable and fruit intake and evidence suggests that high concentrations are generally associated with better cardiometabolic health. At the time we speculated like others that role of the carotenoids may well have been to prevent oxidation of lipid in the lipoproteins and so reduce the uptake of oxidised lipid by macrophages and its deposition within the intimal layers of the major arteries as plaque.It is now widely accepted that CHD is an inflammatory disease and that macrophages within plaque together with tissue damage contribute to this inflammation. Stimulated macrophages release cytokines to activate the immune system both locally and systemically. Precursor complement proteins in the blood are activated to assist immune cells in phagocytosis and cell repair. Individuals with a history of arteriosclerosis display significantly higher concentrations of complement factors C3 and C3a than subjects without such a history. Metabolism of C3 via the alternate complement pathway can give rise to the membrane attack complex (MAC) which creates a hole or pore in pathogens or host cells, killing the cell. Recent studies in patients with early age related macular disease (AMD) who also exhibit similar elevated concentrations of complement proteins in their blood, showed supplementation with lutein progressively decreased the amount of the MAC and other complement factors in the blood. Lutein was used in the supplementation experiments because it is an important constituent of macular pigment. Thus the healthier cardiometabolic features displayed by the people in Toulouse may have been due to the effects of concurrent high concentrations of plasma lutein on the immune system and complement in particular. Other carotenoids may exert similar antioxidant effects but we and others found no differences in antioxidant nutrients between subjects in Toulouse and Belfast or between subjects with asymptomatic markers of atherosclerosis and controls.

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Mechanisms underpinning protection against eccentric exercise-induced muscle damage by ischemic preconditioning

Publication date: Available online 23 November 2016
Source:Medical Hypotheses
Author(s): Alexander Franz, Michael Behringer, Kazunori Nosaka, .Bettina Alexandra Buhren, Holger Schrumpf, Constantin Mayer, Christoph Zilkens, Moritz Schumann
Eccentric exercise training is effective for increasing muscle mass and strength, and improving insulin sensitivity and blood lipid profiles. However, potential muscle damage symptoms such as prolonged loss of muscle function and delayed onset of muscle soreness may restrict the use of eccentric exercise, especially in clinical populations. Therefore, strategies to reduce eccentric exercise-induced muscle damage (EIMD) are necessary, and an extensive number of scientific studies has tried to identify potential intervention modalities to perform eccentric exercises without adverse effects. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which an ischemic preconditioning (IPC) of the extremities may reduce EIMD. IPC consists of an intermittent application of short-time non-lethal ischemia to an extremity (e.g. using a tourniquet) followed by reperfusion and was discovered in clinical settings in an attempt to minimize inflammatory responses induced by blood flow restriction during surgery. The present hypothesis is based on morphological and biochemical similarities in the pathophysiology of skeletal muscle damage during clinical surgery and EIMD. Even though the primary origin of stress differs between I/R-Injury and EIMD, subsequent cellular alterations characterized by an intracellular accumulation of Ca²⁺, an increased production of reactive oxygen species or increased apoptotic signaling are essential elements for both. Moreover, the incipient immune response appears to be similar in I/R-Injury and EIMD, which is indicated by an infiltration of leukocytes into the damaged soft-tissue. Thus far, IPC is considered as a potential intervention strategy in the area of cardiovascular or orthopedic surgery and provides significant impact on soft-tissue protection and downregulation of undesired excessive inflammation induced by I/R-Injury. Based on the known major impact of IPC on skeletal muscle physiology and immunology, the present paper aims to illustrate the potential protective effects of IPC on EIMD by discussing possible underlying mechanisms.

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Relative imbalance as etiology of laryngomalacia – a new theory

Publication date: Available online 23 November 2016
Source:Medical Hypotheses
Author(s): Alok Rathi, Shweta Rathi
Laryngomalacia literally means weak larynx. It is the most common cause of noisy breathing in infants and children constituting around 70% of cases. Its aetiology is not clear and various theories are proposed. Treatment remains following the child with regular weight monitoring in view of expected spontaneous resolution. However we cannot predict which child will resolve spontaneously and which child may need surgical intervention. We propose a new theory based on relative imbalance of demand supply of air, suggesting the increase in demand causing turbulent airflow, increasing suction pressure and causing collapse of laryngeal structures. This theory also helps us in predicting early, which child will resolve spontaneously and which child will need surgery. The methodology to evaluate hypothesis along with techniques and tools are also suggested.

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Reply to: A Phase 2 Randomised Controlled Trial of Nicotinamide for Skin Cancer Chemoprevention in Renal Transplant Recipients

Abstract

We have read with interest the paper by Chen et al. in which oral nicotinamide is used to prevent keratinocyte carcinomas (KC; basal and squamous cell carcinomas of the skin) in renal transplant patients.¹ The current study suggests nicotinamide is safe and effective to prevent the development of KC in this high-risk group, similarly to a study by the same group in non-transplant patients (ONTRAC study, Oral Nicotinamide To Reduce Actinic Cancer).

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Flexible head-casts for high spatial precision MEG

Publication date: Available online 22 November 2016
Source:Journal of Neuroscience Methods
Author(s): Sofie S. Meyer, James Bonaiuto, Mark Lim, Holly Rossiter, Sheena Waters, David Bradbury, Sven Bestmann, Matthew Brookes, Martina F. Callaghan, Nikolaus Weiskopf, Gareth R. Barnes
BackgroundIn combination with magnetoencephalographic (MEG) data, accurate knowledge of the brain's structure and location provide a principled way of reconstructing neural activity with high temporal resolution. However, measuring the brain's location is compromised by head movement during scanning, and by fiducial-based co-registration with magnetic resonance imaging (MRI) data. The uncertainty from these two factors introduces errors into the forward model and limit the spatial resolution of the data.New MethodWe present a method for stabilizing and reliably repositioning the head during scanning, and for co-registering MRI and MEG data with low error.ResultsUsing this new flexible and comfortable subject-specific head-cast prototype, we find within-session movements of <0.25mm and between-session repositioning errors around 1mm.Comparison with Existing Method(s)This method is an improvement over existing methods for stabilizing the head or correcting for location shifts on- or off-line, which still introduce approximately 5mm of uncertainty at best (Adjamian et al., 2004; Stolk et al., 2013; Whalen et al., 2008). Further, the head-cast design presented here is more comfortable, safer, and easier to use than the earlier 3D printed prototype, and give slightly lower co-registration errors (Troebinger et al., 2014b).ConclusionsWe provide an empirical example of how these head-casts impact on source level reproducibility. Employment of the individual flexible head-casts for MEG recordings provide a reliable method of safely stabilizing the head during MEG recordings, and for co-registering MRI anatomical images to MEG functional data.

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Reply to: A Phase 2 Randomised Controlled Trial of Nicotinamide for Skin Cancer Chemoprevention in Renal Transplant Recipients

Abstract

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[Supraglottoplasty for pediatric laryngomalacia : Results from 71 cases].

[Supraglottoplasty for pediatric laryngomalacia : Results from 71 cases].

HNO. 2016 Nov 21;

Authors: Di Dio D, Amrhein P, Koitschev A, Sittel C

Abstract
Laryngomalacia is the most common cause of stridor in infants. The stridor is caused by an inward collapse of supraglottic structures during inspiration resulting in an inspiratory stridor. The exact etiology still remains unclear. The surgical procedure of choice for laryngomalacia is supraglottoplasty. From 2009 to 2016 a total of 71 children were treated by supraglottoplasty in the department for pediatric otorhinolaryngology of the Stuttgart Hospital. The indications for supraglottoplasty were laryngomalacia with severe inspiratory stridor, oxygen desaturation, suprasternal or chest retraction, feeding difficulties and/or failure to thrive. The overall success rate was 86 % but there was a clear difference between children with isolated laryngomalacia and the group with associated comorbidities. The success rate for patients with isolated laryngomalacia was 98 % and for patients with associated comorbidities 57 %. Supraglottoplasty is therefore an effective and safe treatment for symptomatic laryngomalacia and a reduction in the success rate showed a clear correlation with the presence of congenital comorbidities.

PMID: 27872941 [PubMed - as supplied by publisher]

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Integration of isothermal amplification methods in microfluidic devices: Recent advances

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Maria Chiara Giuffrida, Giuseppe Spoto
The integration of nucleic acids detection assays in microfluidic devices represents a highly promising approach for the development of convenient, cheap and efficient diagnostic tools for clinical, food safety and environmental monitoring applications. Such tools are expected to operate at the point-of-care and in resource-limited settings.The amplification of the target nucleic acid sequence represents a key step for the development of sensitive detection protocols. The integration in microfluidic devices of the most popular technology for nucleic acids amplifications, polymerase chain reaction (PCR), is significantly limited by the thermal cycling needed to obtain the target sequence amplification. This review provides an overview of recent advances in integration of isothermal amplification methods in microfluidic devices. Isothermal methods, that operate at constant temperature, have emerged as promising alternative to PCR and greatly simplify the implementation of amplification methods in point-of-care diagnostic devices and devices to be used in resource-limited settings. Possibilities offered by isothermal methods for digital droplet amplification are discussed.

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Recent advances in DNA-based electrochemical biosensors for heavy metal ion detection: A review

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): M.R. Saidur, A.R. Abdul Aziz, W.J. Basirun
The presence of heavy metal in food chains due to the rapid industrialization poses a serious threat on the environment. Therefore, detection and monitoring of heavy metals contamination are gaining more attention nowadays. However, the current analytical methods (based on spectroscopy) for the detection of heavy metal contamination are often very expensive, tedious and can only be handled by trained personnel. DNA biosensors, which are based on electrochemical transduction, is a sensitive but inexpensive method of detection. The principles, sensitivity, selectivity and challenges of electrochemical biosensors are discussed in this review. This review also highlights the major advances of DNA-based electrochemical biosensors for the detection of heavy metal ions such as Hg²⁺, Ag⁺, Cu²⁺ and Pb²⁺.

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A dual-potential electrochemiluminescence ratiometric sensor for sensitive detection of dopamine based on graphene-CdTe quantum dots and self-enhanced Ru(II) complex

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Xiaomin Fu, Xingrong Tan, Ruo Yuan, Shihong Chen
A novel dual-potential ratiometric electrochemiluminescence (ECL) sensor was designed for detecting dopamine (DA) based on graphene-CdTe quantum dots (G-CdTe QDs) as the cathodic emitter and self-enhanced Ru(II) composite (TAEA-Ru) as the anodic emitter. TAEA-Ru was prepared by linking ruthenium(II) tris(2,2′-bipyridyl-4,4′-dicarboxylato) with tris(2-aminoethyl)amine. Firstly, 3-aminopropyltriethoxysilane founctionalized G-CdTe QDs was used as the substrate for capturing target DA via the specific recognition of the diol of DA to the oxyethyl group of APTES. Then, Cu2O nanocrystals supported TAEA-Ru was further bound by the strong interaction between amino groups of DA and carboxyl groups of the Cu2O-TAEA-Ru. With the increase in DA concentration, the loading of Cu2O-TAEA-Ru at the electrode increased. As a result, the anodic ECL signal from TAEA-Ru increased, and the cathodic ECL signal from G-CdTe QDs/O2 system decreased correspondingly. Such a decrease was resulted from the ECL resonance energy transfer (RET) from G-CdTe QDs to TAEA-Ru as well as the dual quenching effects of Cu2O to G-CdTe QDs, namely the ECL-RET from G-CdTe QDs to Cu2O and the consumption of coreactant O2 by Cu2O. Based on the ratio of two ECL signals, the determination of DA was achieved with a linear range from 10.0 fM to 1.0nM and a detection limit low to 2.9 fM (S/N=3). The combination of G-CdTe QDs/O2 and TAEA-Ru would break the limitation of the same coreatant shared in previous ECL ratiometric systems and provide a potential application of ECL ratiometric sensor in the detection of biological small molecules with the assistance of the dual molecular recognition strategy.

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MnO2 nanosheets as an artificial enzyme to mimic oxidase for rapid and sensitive detection of glutathione

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Jing Liu, Lingjie Meng, Zhaofu Fei, Paul J. Dyson, Xunan Jing, Xing Liu
Nanozymes are increasingly used as components in assays and diagnostics. Here, we describe a rapid and highly sensitive colorimetric assay for the detection and quantification of glutathione (GSH) employing MnO2 nanosheets as an artificial oxidase. In the assay pale yellow 3,3´,5,5´-tetramethylbenzidine (TMB) is oxidized to a blue product (oxTMB) under catalyzing of MnO2 nanosheets with a significant change in absorption at 650nm. GSH selectively inhibits this reaction with a detection limit of 300nM. The high specificity of inhibition by GSH allows this system to be used to determine the GSH concentrations in human serum samples. The MnO2 nanosheet-based assay is simple, rapid, sensitive and selective for the quantification of GSH and surpasses detection methods based on other MnO2 nanomaterials.

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Molecular visualizing and quantifying immune-associated peroxynitrite fluxes in phagocytes and mouse inflammation model

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Zan Li, Shi-Hai Yan, Chen Chen, Zhi-Rong Geng, Jia-Yin Chang, Chun-Xia Chen, Bing-Huan Huang, Zhi-Lin. Wang
Reactions of peroxynitrite (ONOO⁻) with biomolecules can lead to cytotoxic and cytoprotective events. Due to the difficulty of directly and unambiguously measuring its levels, most of the beneficial effects associated with ONOO⁻ in vivo remain controversial or poorly characterized. Recently, optical imaging has served as a powerful noninvasive approach to studying ONOO⁻ in living systems. However, ratiometric probes for ONOO⁻ are currently lacking. Herein, we report the design, synthesis, and biological evaluation of F482, a novel fluorescence indicator that relies on ONOO⁻-induced diene oxidation. The remarkable sensitivity, selectivity, and photostability of F482 enabled us to visualize basal ONOO⁻ in immune-stimulated phagocyte cells and quantify its generation in phagosomes by high-throughput flow cytometry analysis. With the aid of in vivo ONOO⁻ imaging in a mouse inflammation model assisted by F482, we envision that F482 will find widespread applications in the study of the ONOO⁻ biology associated with physiological and pathological processes in vitro and in vivo.

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A low cost and palm-size analyzer for rapid and sensitive protein detection by AC electrokinetics capacitive sensing

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Xiaozhu Liu, Cheng Cheng, Jayne Wu, Shigetoshi Eda, Yongcai Guo
Specific detection of protein biomarkers has a wide range of applications in areas such as medical science, diagnostics, and pharmacology. Quantitative detection of protein biomarkers in biological media, such as serum, is critically important in detecting disease or physiological malfunction, or tracking disease progression. Among various detection methods, electrical detection is particularly well suited for point-of-care (POC) specific protein detection, being of low cost, light weight and small form factor. A portable system for sensitive and quantitative detection of protein biomarkers will be highly valuable in controlling and preventing diseases outbreaks. Recently, an alternating current electrokinetic (ACEK) capacitive sensing method has been reported to demonstrate very promising performance on rapid and sensitive detection of specific protein from serum. In this work, a low cost and portable analyzer with good accuracy is developed to use with ACEK capacitive sensing to produce a true POC technology. The development of a board-level capacitance readout system is presented, as well as the adaption of the protocol for use with ACEK capacitive sensing. Results showed that the developed system could achieve a limit of detection of 10ng/mL, comparable to a sophisticated benchtop instrument. With its small size and light-weight similar to a smart phone, the developed system is ready to be applicable to POC diagnostics. Further, the readout system can be readily expanded for multichannel monitoring and telecommunication capabilities.

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A symmetric supercapacitor/biofuel cell hybrid device based on enzyme-modified nanoporous gold: An autonomous pulse generator

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Xinxin Xiao, Peter Ó Conghaile, Dónal Leech, Roland Ludwig, Edmond Magner
The integration of supercapacitors with enzymatic biofuel cells (BFCs) can be used to prepare hybrid devices in order to harvest significantly higher power output. In this study, a supercapacitor/biofuel cell hybrid device was prepared by the immobilisation of redox enzymes with electrodeposited poly(3,4-ethylenedioxythiophene) (PEDOT) and the redox polymer [Os(2,2′-bipyridine)2(polyvinylimidazole)10Cl]^+/2+(Os(bpy)2PVI) on dealloyed nanoporous gold. The thickness of the deposition layer can be easily controlled by tuning the deposition conditions. Once charged by the internal BFC, the device can be discharged as a supercapacitor at a current density of 2mAcm⁻² providing a maximum power density of 608.8μWcm⁻², an increase of a factor of 468 when compared to the power output from the BFC itself. The hybrid device exhibited good operational stability for 50 charge/discharge cycles and ca. 7h at a discharge current density of 0.2mAcm⁻². The device could be used as a pulse generator, mimicking a cardiac pacemaker delivering pulses of 10μA for 0.5ms at a frequency of 0.2Hz.

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An end-point method based on graphene oxide for RNase H analysis and inhibitors screening

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Chuan Zhao, Jialong Fan, Lan Peng, Lijian Zhao, Chunyi Tong, Wei Wang, Bin Liu
As a highly conserved damage repair protein, RNase H can hydrolysis DNA-RNA heteroduplex endonucleolytically and cleave RNA-DNA junctions as well. In this study, we have developed an accurate and sensitive RNase H assay based on fluorophore-labeled chimeric substrate hydrolysis and the differential affinity of graphene oxide on RNA strand with different length. This end-point measurement method can detect RNase H in a range of 0.01 to 1 units /mL with a detection limit of 5.0×10^-3 units/ mL under optimal conditions. We demonstrate the utility of the assay by screening antibiotics, resulting in the identification of gentamycin, streptomycin and kanamycin as inhibitors with IC50 of 60±5µM, 70±8µM and 300±20µM, respectively. Furthermore, the assay was reliably used to detect RNase H in complicated biosamples and found that RNase H activity in tumor cells was inhibited by gentamycin and streptomycin sulfate in a concentration-dependent manner. The average level of RNase H in serums of HBV infection group was similar to that of control group. In summary, the assay provides an alternative tool for biochemical analysis for this enzyme and indicates the feasibility of high throughput screening inhibitors of RNase H in vitro and in vivo.

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Paper-based enzymatic electrode with enhanced potentiometric response for monitoring glucose in biological fluids

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Marc Parrilla, Rocío Cánovas, Francisco J. Andrade
A novel paper-based potentiometric sensor with an enhanced response for the detection of glucose in biological fluids is presented. The electrode consists on platinum sputtered on a filter paper and a Nafion membrane to immobilize the enzyme glucose oxidase. The response obtained is proportional to the logarithm of the concentration of glucose, with a sensitivity of −119±8mV·decade⁻¹, a linear range that spans from 10⁻⁴M to 10^−2.5 M and a limit of detection of 10^−4.5 M of glucose. It is shown that Nafion increases the sensitivity of the technique while minimizing interferences. Validation with human serum samples shows an excellent agreement when compared to standard methods. This approach can become an interesting alternative for the development of simple and affordable devices for point of care and home-based diagnostics.

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A fluorescent probe for the efficient discrimination of Cys, Hcy and GSH based on different cascade reactions

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Ying Li, Weimin Liu, Panpan Zhang, Hongyan Zhang, Jiasheng Wu, Jiechao Ge, Pengfei Wang
A fluorescent probe (1) for distinguishing amongst biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), is developed based on different cascade reactions. The key design feature of fluorescent probe 1 is the integration of two potential reaction groups for the thiol and amino groups of biothiols in one molecule. By reacting with the halogen atom and α, β-unsaturated malonitrile in probe 1, Cys, Hcy and GSH can generate a total of three main products with distinct photophysical properties. Probe 1 shows a strong fluorescence turn-on response to Cys with blue–green emission by using an excitation wavelength of 390nm. At an excitation wavelength of 500nm, probe 1 responds to GSH over Cys and Hcy and emits strong orange fluorescence. The discrimination of biothiols can be demonstrated by cell imaging experiments, indicating that probe 1 can be a useful tool for the selective imaging of Cys and GSH in living cells.

Graphical abstract

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A lifetime-sensitive fluorescence anisotropy probe for DNA-based bioassays: The case of SYBR Green

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Benoit Chovelon, Emmanuelle Fiore, Patrice Faure, Eric Peyrin, Corinne Ravelet
In standard steady-state fluorescence anisotropy (FA) DNA-based assays, the ligand binding to a given receptor is typically signalled by the rotational correlation time changes of the tracer. Herein, we report a radically different strategy that relies on the peculiar excited state lifetime features of the SYBR Green (SG) dye. This DNA-binding probe exhibits a drastically short lifetime in solution, leading to a high FA signal. Its complexation to oligonucleotides determines a singular and very large depolarization depending on the concerted effects of extreme lifetime enhancement and resonance energy homotransfer. On the basis of ligand-induced changes in the molar fractions of bound and free forms of SG, the approach provides an unprecedented means for the FA monitoring of the ligand binding to short DNA molecules, allowing the elaboration of a variety of intercalator displacement assays and label-free biosensors that involve diverse DNA structures (duplex, hairpin, G-quadruplex and single-stranded), ligand types (ion, small organic molecule and protein) and binding modes (intercalation, minor groove, allosteric switch). These findings open up promising avenues in the design of a new generation of FA assays.

Graphical abstract

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One-step separation-free detection of carcinoembryonic antigen in whole serum: Combination of two-photon excitation fluorescence and optical trapping

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Cheng-Yu Li, Di Cao, Chu-Bo Qi, Hong-Lei Chen, Ya-Tao Wan, Yi Lin, Zhi-Ling Zhang, Dai-Wen Pang, Hong-Wu Tang
Direct analysis of biomolecules in complex biological samples remains a major challenge for fluorescence-based approaches due to the interference of background signals. Herein, we report an analytical methodology by exploiting a single low-cost near-infrared sub-nanosecond pulse laser to synchronously actualize optical trapping and two-photon excitation fluorescence for senstive detection of carcinoembryonic antigen (CEA) in buffer solution and human whole serum with no separation steps. The assay is performed by simultaneously trapping and exciting the same immune-conjugated microsphere fabricated with a sandwich immunization strategy. Since the signal is strictly limited in the region of a three-dimensional focal volume where the microsphere is trapped, no obvious background signal is found to contribute the detected signals and thus high signal-to-background data are obtained. As a proof-of-concept study, the constructed platform exhibits good specificity for CEA and the detection limit reaches as low as 8pg/mL (45 fM) with a wide linear range from 0.01 to 60ng/mL in the both cases. To investigate the potential application of this platform in clinical diagnosis, 15 cases of serum samples were analyzed with satisfactory results, which further confirm the applicability of this method.

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Multifunctional nanoparticles for protein detections in thin channels

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Hweiyan Tsai, Weimin Lin, Mingchieh Chuang, Yishuan Lu, C. Bor Fuh
This paper presents a method for simultaneous detection of two proteins by using multifunctional nanoparticles with a magnetic immunoassay in thin channels. Biofunctional magnetic graphene quantum dots (GQDs) combined with two biofunctional quantum dots (QDs) were used for simultaneously detecting two proteins. Magnetic GQDs enabled selective and quantitative nanoparticle deposition with blue emission. Biofunctional QDs confirmed the two protein detections with orange and green emissions. We used two model biomarkers [alpha-fetoprotein (AFP) and cancer antigen 125 (CA125)] to demonstrate the feasibility of the proposed method. The detection limits (0.06pg/mL AFP and 0.001U/mL CA125) and linear ranges (0.2pg/mL-0.68ng/mL AFP and 0.003–25U/mL CA125) of this method are the same as those of single protein detection within experimental errors. These detection limits are substantially lower and the linear ranges are considerably wider than those of enzyme-linked immunosorbent assay (ELISA) and other immunoassay methods. The differences between the proposed method and an ELISA method in AFP and CA125 measurements of serum samples were less than 12%. The proposed method demonstrates favorable detection of biomarkers with advantages of speed, sensitivity, selectivity, and throughput.

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Ultrasensitive non enzymatic multiple immunosensor for tumor markers detection by coupling DNA hybridization chain reaction with intercalated molecules

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Jinjin Guo, Junchun Wang, Junjun Zhang, Wenjuan Zhang, Yuzhong Zhang
In this study, we tried coupling the small signal molecules that could intercalate into DNA double helix with hybridization chain reaction (HCR) technique to fabricate a multiple immunosensor. Doxorubicin hydrochloride (DXH) and methylene blue (MB) were used as signal molecules and alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were selected as model biomarkers. The immunosensor mainly consists of three parts as follows: First, two different primary antibodies (Ab1) immobilized on the surface of gold nanoparticles (Au NPs); Second, secondary antibodies (Ab2) conjugated with DNA primer; Third, long DNA concatemers from HCR were used as a carrier to intercalate amounts of signal molecules (DXH or MB). A sandwich immunocomplex was formed among primary antibodies, target biomarkers and secondary antibodies conjugated with DNA primer via specific recognition reaction. Afterwards, DNA concatemers intercalating amounts of DXH or MB were linked to DNA primer via DNA hybridization. Square wave voltammetry (SWV) was employed to record the response signals from electroactive molecules DXH and MB, and two distinguishable signals were obtained, which peak potentials were at about −0.30V (corresponding to MB) and −0.70V (corresponding to DXH, both vs SCE), respectively. The signal intensities of MB and DXH were linearly related to the logarithm of biomarkers concentration in the range of 0.05pgmL⁻¹–25ngmL⁻¹, and the limit of detection were 0.03pgmL⁻¹ for CEA and 0.02pgmL⁻¹ for AFP (at S/N=3), respectively. Furthermore, the immunosensor exhibited a sensitive electrochemical response to biomarkers in human serum samples and the results obtained were in accordance with reference method, indicating the immunosensor can be applied to real sample analysis in clinic diagnosis.

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Label-free piezoelectric biosensor for prognosis and diagnosis of Systemic Lupus Erythematosus

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Noelle M. do Nascimento, Augusto Juste-Dolz, Elena Grau-García, Jose A. Román-Ivorra, Rosa Puchades, Angel Maquieira, Sergi Morais, David Gimenez-Romero
An autoantigen piezoelectric sensor to quantify specific circulating autoantibodies in human serum is developed. The sensor consisted on a quartz crystal microbalance with dissipation monitoring (QCM-D) where TRIM21 and TROVE2 autoantigens were covalently immobilized, allowing the selective determination of autoantibodies for diagnosis and prognosis of Systemic Lupus Erythematosus (SLE). The sensitivity of the biosensor, measured as IC50 value, was 1.51U/mL and 0.32U/mL, for anti-TRIM21 and anti-TROVE2 circulating autoantibodies, respectively. The sensor is also able to establish a structural interaction fingerprint pattern or profile of circulating autoantibodies, what allows scoring accurately SLE patients. Furthermore, a statistical association of global disease activity with TRIM21-TROVE2 interaction was found (n=130 lupic patient samples, p-value=0.0413). The performances of the biosensor were compared with standard ELISA and multiplex DVD-array high-throughput screening assays, corroborating the viability of piezoelectric biosensor as a cost-effective in vitro assay for the early detection, monitoring or treatment of rare diseases.

Graphical abstract

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Self-tuning interfacial architecture for Estradiol detection by surface plasmon resonance biosensor

Publication date: 15 April 2017
Source:Biosensors and Bioelectronics, Volume 90
Author(s): Praskoviya Boltovets, Svitlana Shinkaruk, Luc Vellutini, Borys Snopok
This study reports the operation principles for reusable SPR biosensors utilizing nanoscale-specific electrostatic levitation phenomena in their sensitive layer design. Functional macromolecular building blocks localized near the "charged" surface by a variety of weak electrostatic interactions create a flexible and structurally variable architecture. A proof-of-concept is demonstrated by an immunospecific detection of 17β-Estradiol (E2) following the competitive inhibition format. The sensing interfacial architecture is based on the BSA-E2 conjugate within the BSA matrix immobilized on the "charged" (as a result of guanidine thiocyanate treatment) gold surface at pH 5.0. Kinetic analysis for different E2 concentrations shows that using parameter β of the stretched exponential function ~(1-exp(-(t/τ)^β) as an analyte-specific response measure allows one to substantially decrease the low detection limit (down to 10⁻³ng/ml) and increase the dynamic range (10⁻³–10³ng/ml) of the SPR biosensor. Finally, it's concluded that the created interfacial architecture is a typical complex system, where SPR response is formed by the stochastic interactions within the whole variety of processes in the system. The E2 addition destroys the uniformity of the reaction space (where an interaction of the antibody (Ab) and the analog of E2 in the self-tuneable matrix takes place) by the redistribution of the immunospecific complexes Ab(E2)x (x=0, 1, 2) dependent on E2 concentration. Binding dynamics changes are reflected in the values of β which summarize in compact form all "hidden" information specific for the evolving distributed interfacial system.

http://ift.tt/2gKMan0

Ten years experience with breast reconstruction after salvage mastectomy in previously irradiated patients: analysis of outcomes, satisfaction and well-being

OBJECTIVE: Reconstruction following mastectomy offers women an opportunity to mollify some of the emotional and aesthetic effects of this devastating disease.

PATIENTS AND METHODS: The authors reviewed the files of 83 patients who underwent immediate postmastectomy reconstruction with tissue expander between January of 2003 and June of 2012 at our hospital. The patients were divided into two groups: Group A (study group) included 30 patients with previous quadrantectomy and radiotherapy who underwent salvage mastectomy after local recurrence; Group B (control group) included 53 patients submitted to primary radical mastectomy. We submitted Breast-Q reconstruction post-operative module to all of our patients.

RESULTS: The median follow-up time for the whole group was 36 months (range = 12-144 months). Between group A and group B, there were no significant differences. In the group A, the median time from RT to reconstruction was 24 months (range = 9-192 months). The overall rate of complications was not similar between the two groups (66.6% vs. 58.5%; p = NS). However, the major complications occurred mostly in the irradiated group, showing a trend of statistical significance (53.3% vs. 32.0%; p = 0.07). In this group, the occurrence of major complications was not different according to time from RT to reconstruction (p = 0.313). In particularly, patients from the irradiated group (group A) had a significantly higher risk of grade III-IV capsular contracture (relative risk 3.75, p = 0.02) and autologous salvage reconstruction (relative risk 10.4, p = 0.02).

CONCLUSIONS: The results of this study prove that heterologous reconstruction is still possible following salvage mastectomy in previously irradiated patients.

L'articolo Ten years experience with breast reconstruction after salvage mastectomy in previously irradiated patients: analysis of outcomes, satisfaction and well-being sembra essere il primo su European Review.

http://ift.tt/2gB4Q7s

Some Thyrotropic Agents.

This volume evaluates carcinogenicity to humans of 19 chemicals that are carcinogenic to the thyroid follicular-cell epithelium in rodents. These included some so-called 'anti-thyroid' drugs (methimazole, methylthiouracil, propylthiouracil and thiouracil); some sedatives (doxylamine succinate and phenobarbital); and some other drugs including the systemic antifungal antibiotic griseofulvin, the diuretic spironolactone, and the antibacterial sulfa drugs sulfamethazine and sulfamethoxazole. Other chemicals are or have been used in agriculture as pesticides (amitrole, chlordane/heptachlor, hexachlo-robenzene and toxaphene), in foods and cosmetics (kojic acid), in hair dyes (2,4-diaminoanisole) or as industrial chemicals (N,N'-diethylthiourea, ethylenethiourea and thiourea).

http://ift.tt/2gkdiFN

A Phase II Study of Pembrolizumab in Refractory Advanced Esophageal Cancer

Conditions: Esophageal Cancer; Squamous Cell Esophagus Cancer; Adenocarcinoma Esophagus
Intervention: Drug: Pembrolizumab
Sponsors: Dana-Farber Cancer Institute; Merck Sharp & Dohme Corp.
Not yet recruiting - verified November 2016

http://ift.tt/2f6pvjC

Cognitive Style and Mobile Technology in E-learning in Undergraduate Medical Education

Condition: Medical Education
Intervention: Other: mobile technology of e-learning (M-TEL)
Sponsors: Chang Gung Memorial Hospital; Ministry of Science and Technology, Taiwan
Not yet recruiting - verified November 2016

http://ift.tt/2foFULK

Chemoradiation Versus Esophagectomy for Locally Advanced Esophageal Cancer

Condition: Esophagus Cancer
Interventions: Procedure: CRT; Procedure: surgery
Sponsors: The First Affiliated Hospital of Henan University of Science and Technology; Jiangsu HengRui Medicine Co., Ltd.; Anyang Tumor Hospital; 150th Hospital of PLA
Not yet recruiting - verified November 2016

http://ift.tt/2f6rTa3

A Phase II Study of Pembrolizumab in Refractory Advanced Esophageal Cancer

Cognitive Style and Mobile Technology in E-learning in Undergraduate Medical Education

Chemoradiation Versus Esophagectomy for Locally Advanced Esophageal Cancer

Seborrheic Keratoses as the First Sign of Bladder Carcinoma: Case Report of Leser-Trélat Sign in a Rare Association with Urinary Tract Cancer

Introduction. Skin disorders can be the first manifestation of occult diseases. The recognition of typical paraneoplastic dermatoses may anticipate the cancer diagnosis and improve its prognosis. Although rarely observed, the sudden appearance and/or rapid increase in number and size of seborrheic keratoses can be associated with malignant neoplasms, known as the sign of Leser-Trélat. The aim of this report is to unveil a case of a patient whose recently erupted seborrheic keratoses led to investigation and consequent diagnosis of bladder cancer. Case Presentation. A 67-year-old man was admitted to the intensive care unit due to an exacerbation of chronic obstructive pulmonary disease (COPD). On physical examination, multiple seborrheic keratoses on the back of the hands, elbows, and trunk were observed; the patient had a 4-month history of these lesions yet was asymptomatic. The possibility of Leser-Trélat syndrome justified the investigation for neoplasia, and a bladder carcinoma was detected by CT-scan. The patient denied previous hematuria or any other related symptoms. Many of the lesions regressed during oncologic treatment. Conclusion. Despite the critics on the validity of the sign of Leser-Trélat, our patient fulfills the description of the disease, though urinary malignancy is a rare association. That corroborates the need of further investigation when there is a possibility of paraneoplastic manifestation.

http://ift.tt/2gkezg6

Traumatic Pseudoaneurysm of the Internal Maxillary Artery: A Rare Life-Threatening Hemorrhage as a Complication of Maxillofacial Fractures

Pseudoaneurysm of the internal maxillary artery due to a traumatic event is a rare condition. Pseudoaneurysms are usually directly produced by arteries break with extravasation of blood. The compressed perivascular tissue forms the wall of aneurysmal sac. Then, this sac gradually expands and can be damaged. It is rare to see pseudoaneurysms of IMA. They are usually associated with fracture of the neck of the mandible. To the best of our knowledge the pseudoaneurysm of the internal maxillary artery related to maxillofacial trauma is an event extremely rare in the literature and if not quickly managed can lead to the patient's death. This case underlines how the close cooperation between surgeons and radiologists results in a quick diagnosis and management of such pathological events.

http://ift.tt/2fr6o2l

The Yin and Yang of nucleic acid-based therapy in the brain

Publication date: Available online 22 November 2016
Source:Progress in Neurobiology
Author(s): Stefano Gustincich, Silvia Zucchelli, Antonello Mallamaci
The post-genomic era has unveiled the existence of a large repertory of non-coding RNAs and repetitive elements that play a fundamental role in cellular homeostasis and dysfunction. These may represent unprecedented opportunities to modify gene expression at the right time in the correct space in vivo, providing an almost unlimited reservoir of new potential pharmacological agents. Hijacking their mode of actions, the druggable genome can be extended to regulatory RNAs and DNA elements in a scalable fashion.Here, we discuss the state-of-the–art of nucleic acid-based drugs to treat neurodegenerative diseases. Beneficial effects can be obtained by inhibiting (Yin) and increasing (Yang) gene expression, depending on the disease and the drug target. Together with the description of the current use of inhibitory RNAs (small inhibitory RNAs and antisense oligonucleotides) in animal models and clinical trials, we discuss the molecular basis and applications of new classes of activatory RNAs at transcriptional (RNAa) and translational (SINEUP) levels.

http://ift.tt/2f6npAc

CO2: Editorial Board/Subscription info.

Publication date: December 2016
Source:Progress in Neurobiology, Volume 147

http://ift.tt/2f6itvb

Evidence of microbiota dysbiosis in chronic rhinosinusitis

Background

Despite considerable research, the pathogenesis of chronic rhinosinusitis (CRS) remains poorly understood. Potential microbial roles in the etiology or progression of CRS have long been hypothesized, yet few specific associations have been identified. In this study we investigate associations between patterns in resident bacterial communities and clinical variants of CRS.

Methods

Bacterial communities were assessed in 94 patients with extensive bilateral CRS undergoing endoscopic sinus surgery (ESS) and 29 controls undergoing ESS for indications other than CRS. Patients were grouped on the basis of phenotypic variants (with or without polyposis) and clinical parameters, including asthma and cystic fibrosis. Bacterial communities were characterized via 16S rRNA gene amplicon sequencing, and quantified by quantitative polymerase chain reaction.

Results

Controls and idiopathic CRS subjects tended to be dominated by members of the genera Corynebacterium and Staphylococcus, together with lower abundances of several other genera, including Streptococcus, Moraxella, and Haemophilus. Aberrant (dysbiotic) bacterial assemblages (with changes in community membership and structure, reduced diversity, and increased bacterial load) and increased inter- and intrasubject variability were more common in subjects with comorbidities such as asthma and cystic fibrosis. Dysbiotic communities were variably dominated by members of the genera Staphylococcus, Streptococcus, Haemophilus, Pseudomonas, Moraxella, or Fusobacterium.

Conclusion

Bacterial community dysbiosis was more apparent than specific associations with examined phenotypes or endotypes, and may play a role in the pathogenesis or influence the severity of CRS. Reductions in several common core bacterial taxa, increased inter- and intrasubject variability, reduced bacterial diversity, and increased bacterial load characterized aberrant bacterial communities in CRS.

http://ift.tt/2fF4pVJ

Afatinib: A Review in Advanced Non-Small Cell Lung Cancer

Abstract

Afatinib (Giotrif^®, Gilotrif^®) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. In the first-line treatment of patients with advanced lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations, afatinib significantly prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS), compared with gefitinib (LUX-Lung 7 trial). In the overall population of patients receiving first-line treatment for advanced lung adenocarcinoma with activating EGFR mutations, afatinib significantly prolonged PFS, but not OS, compared with pemetrexed plus cisplatin (LUX-Lung 3 trial) or gemcitabine plus cisplatin (LUX-Lung 6 trial). However, in both LUX-Lung 3 and LUX-Lung 6, OS was significantly prolonged in the subgroup of patients with deletions in exon 19 receiving afatinib versus chemotherapy. In the second-line treatment of advanced squamous non-small cell lung cancer (NSCLC), afatinib significantly prolonged PFS and OS, compared with erlotinib, regardless of EGFR mutation status (LUX-Lung 8 trial). Afatinib had a predictable and manageable tolerability profile in patients with advanced NSCLC. In conclusion, afatinib is an important option for the first-line treatment of patients with advanced NSCLC and activating EGFR mutations, and provides an additional option for the treatment of patients with squamous NSCLC that has progressed following first-line platinum-based chemotherapy.

http://ift.tt/2gAyMRe

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

Background

Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs.

Methods

We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD patients in a prospective single-arm intervention study of ESS with adjuvant therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks of systemic antibiotics. Additional treatment with local colistin for 6 months was instigated when P. aeruginosa was cultured at ESS.

Results

Twenty-four PCD patients underwent ESS to search for an infectious focus (n = 10), due to severe symptoms of CRS (n = 8), or both (n = 6). Bacteria were cultured from sinus samples in 21 patients (88%), and simultaneous sinus and lung colonization with identical pathogens were observed in 13 patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS.

Conclusion

We demonstrated an improvement in CRS-related symptoms after ESS and adjuvant therapy. In selected PCD patients, the suggested regimen may postpone chronic lung infection with P. aeruginosa and stabilize lung function.

http://ift.tt/2ggNOLx

The role of fillers in aesthetic medicine: medico-legal aspects

In recent years there has been an exponential increase of fillers use in aesthetic medicine. The popularity of this anti-wrinkle product is based on their capacity to offer significant improvement in the aesthetic field, particularly to skin rejuvenating processes with non-invasive and less expensive techniques, if compared to the surgical methods (i.e. surgical lifting). The great number of fillers on the market is composed of a large heterogenic number of biomaterials. The aim of this review was to provide an overview and a classification of the filling materials that are most commonly used. A synthesis of the literature concerning fillers and related side effects was also reported. The law decree no. 23 of 1998, converted in the law no. 94 of 1998 and the principal judgments of the Italian Court of Cassation have been examined with the medico-legal issues related to fillers use in medicine. With respect to their degradation, filler materials may be classified as temporary (degradable), semi-permanent and permanent (not degradable). The temporary fillers such as hyaluronic acid and collagen are completely degraded by the surrounding tissue in a few months. The permanent fillers, such as the ones derived from silicon oil and minerals are not biodegradable and may cause serious and irreversible side effects. Their use requires a physician with a high level of specialization to perform the treatment, a deep knowledge of face anatomy and a great degree of experience.

L'articolo The role of fillers in aesthetic medicine: medico-legal aspects sembra essere il primo su European Review.

http://ift.tt/2f6lr2T

Evidence of microbiota dysbiosis in chronic rhinosinusitis

Background

Methods

Results

Conclusion

http://ift.tt/2fF4pVJ

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

Background

Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs.

Methods

Results

Conclusion

http://ift.tt/2ggNOLx

Cellular Responses to Replication Stress: Implications in Cancer Biology and Therapy

Publication date: Available online 22 November 2016
Source:DNA Repair
Author(s): Hui-Ju Hsieh, Guang Peng
DNA replication is essential for cell proliferation. Any obstacles during replication cause replication stress, which may lead to genomic instability and cancer formation. In this review, we summarize the physiological DNA replication process and the normal cellular response to replication stress. We also outline specialized therapies in clinical trials based on current knowledge and future perspectives in the field.

http://ift.tt/2g3gtR6

Crusted impetigo-like lesion on the face: A case of IgG/IgA pemphigus

In recent years, cases of IgG/IgA pemphigus, a rare subtype of pemphigus characterized by circulating IgG and IgA autoantibodies against the keratinocyte cell surface have been reported.^1-6 The cutaneous manifestations of IgG/IgA pemphigus were reported to resemble those of IgA pemphigus in form, including the presence of pustules and annular lesions.¹ However, no consensus on what eruptions are typical of IgG/IgA pemphigus has been established, due to the rarity of this disease. In this report, we describe a case of IgG/IgA pemphigus who developed severe crusted lesions on the seborrheic area that closely resembled facial crusted impetigo.

http://ift.tt/2glyT00

Quality of Life Measurement in Atopic Dermatitis. Position Paper of the European Academy of Dermatology and Venereology (EADV) Task Force on Quality of Life

Abstract

There is a need for researchers to have easy reference to the wide spectrum of different types of quality of life (QoL) instruments that can be used in atopic dermatitis (AD). Previous reviews on QoL in AD do not cover the full spectrum of QoL measures used in studies on AD. This paper, on behalf of the European Academy of Dermatology and Venereology (EADV) Task Force on QoL contains information on instruments available for health-related QoL and family QoL assessment in AD including information on validation, experience of QoL assessment in AD for different purposes, peculiarities of QoL assessment in different age groups, expert analysis of available instruments including data on limitations of their use and recommendations of the Task Force.

http://ift.tt/2gKFDbU

Epidemiological, dermoscopical and pathological evaluation of melanocytic lesions of the buttock in a 5-year period: a female prevalence

A self-assessment of the skin plays a pivotal role in the early diagnosis of melanoma. However, when pigmented lesions are located on hidden areas or on locations that are difficult to self-examine, their assessment becomes more difficult.

http://ift.tt/2glBHue

Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014

Publication date: January 2017
Source:European Journal of Cancer, Volume 70
Author(s): Amanda-Louise Fenger Carlander, Christian Grønhøj Larsen, David Hebbelstrup Jensen, Emilie Garnæs, Katalin Kiss, Luise Andersen, Caroline Holkmann Olsen, Maria Franzmann, Estrid Høgdall, Susanne K. Kjær, Bodil Norrild, Lena Specht, Elo Andersen, Thomas van Overeem Hansen, Finn Cilius Nielsen, Christian von Buchwald
BackgroundHuman papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020.Patients and methodsPatients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing.ResultsSixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV–) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67.ConclusionAn increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV– cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark.

http://ift.tt/2g34DX9

Nuclear transportation of exogenous epidermal growth factor receptor and androgen receptor via extracellular vesicles

Publication date: January 2017
Source:European Journal of Cancer, Volume 70
Author(s): Jolene Read, Alistair Ingram, Hassan A. Al Saleh, Khrystyna Platko, Kathleen Gabriel, Anil Kapoor, Jehonathan Pinthus, Fadwa Majeed, Talha Qureshi, Khalid Al-Nedawi
Epidermal growth factor receptor (EGFR) plays a central role in the progression of several human malignancies. Although EGFR is a membrane receptor, it undergoes nuclear translocation, where it has a distinct signalling pathway. Herein, we report a novel mechanism by which cancer cells can directly transport EGFR to the nucleus of other cells via extracellular vesicles (EVs). The transported receptor is active and stimulates the nuclear EGFR pathways. Interestingly, the translocation of EGFR via EVs occurs independently of the nuclear localisation sequence that is required for nuclear translocation of endogenous EGFR. Also, we found that the mutant receptor EGFRvIII could be transported to the nucleus of other cells via EVs. To assess the role of EVs in the regulation of an actual nuclear receptor, we studied the regulation of androgen receptor (AR). We found that full-length AR and mutant variant ARv7 are secreted in EVs derived from prostate cancer cell lines and could be transported to the nucleus of AR-null cells. The EV-derived AR was able to bind the androgen-responsive promoter region of prostate specific antigen, and recruit RNA Pol II, an indication of active transcription. The nuclear-translocated AR via EVs enhanced the proliferation of acceptor cells in the absence of androgen. Finally, we provide evidence that nuclear localisation of AR could occur in vivo via orthotopically-injected EVs in male SCID mice prostate glands. To our knowledge, this is the first study showing the nuclear translocation of nuclear receptors via EVs, which significantly extends the role of EVs as paracrine transcriptional regulators.

http://ift.tt/2fQXbRt

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τετάρτη 23 Νοεμβρίου 2016

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Αρχειοθήκη ιστολογίου