Common electronic origin of superconductivity in (Li,Fe)OHFeSe bulk superconductor and single-layer FeSe/SrTiO3 films

Article

The mechanism of high-temperature superconductivity in the iron-based materials remains not fully understood. Here, the authors report on ARPES measurements on an FeSe-based bulk superconductor, whose electronic properties are found to be similar to those of single-layer FeSe/STO films.

Nature Communications doi: 10.1038/ncomms10608

Authors: Lin Zhao, Aiji Liang, Dongna Yuan, Yong Hu, Defa Liu, Jianwei Huang, Shaolong He, Bing Shen, Yu Xu, Xu Liu, Li Yu, Guodong Liu, Huaxue Zhou, Yulong Huang, Xiaoli Dong, Fang Zhou, Kai Liu, Zhongyi Lu, Zhongxian Zhao, Chuangtian Chen, Zuyan Xu, X. J. Zhou

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1Xf6xmX
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/23U3lla
via IFTTT

EXPOSURE TO POLYBROMINATED DIPHENYL ETHERS ASSOCIATES WITH HYPOTHYROIDISM

EXPOSURE TO POLYBROMINATED DIPHENYL ETHERS ASSOCIATES WITH HYPOTHYROIDISM

Oulhote Y1, Chevrier J1, Bouchard MF Exposure to Polybrominated Diphenyl Ethers (PBDEs) and Hypothyroidism in Canadian Women. J Clin Endocrinol Metab. 2016 Feb;101(2):590-8. doi: 10.1210/jc.2015-2659. Epub 2015 Nov 25.
Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a wide range of products, resulting in widespread human exposure. Epidemiological studies in some populations reported exposure to PBDEs and thyroid hormone levels but little epidemiological data are available among women from the general population.A total of 745 women representative of Canadian women aged 30-79 years participated in a study. We estimated the prevalence ratios (PRs) for hypothyroidism in relation to plasma concentrations of BDE-47, -99, -100, and -153 and their sum (ΣPBDEs). Women were identified as cases if they reported a doctor-diagnosed thyroid condition and underwent thyroid hormone replacement therapy (n = 90).Higher plasma levels of brominated diphenyl ether (BDE)-47 and -100 and ΣPBDEs were associated with an increased prevalence of hypothyroidism. The PR for a 10-fold increase in ΣPBDEs was 1.7 (95% confidence interval [CI] 1.0, 3.0). Associations were consistently higher among women aged 30-50 years than among those 51-79 years for ΣPBDEs and the other PBDE congeners, although the interaction was significant only for BDE-100. For instance, in the younger age group, women with detectable levels of BDE-100 had a PR of 3.8 (95% CI 1.2, 12.3) compared with women with undetectable levels; the corresponding PR in the older age group was 1.2 (95% CI 0.6, 2.3). No association was observed for BDE-99 and -153.
Plasma PBDE levels were associated with an increased prevalence of hypothyroidism in Canadian women aged 30-50 years. Although the cross-sectional design of the study limits inferences of causality, these findings have important implications, given the key role of thyroid hormones in several biological mechanisms during reproductive age.

The post EXPOSURE TO POLYBROMINATED DIPHENYL ETHERS ASSOCIATES WITH HYPOTHYROIDISM appeared first on Thyroid Disease Manager.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1UZUSqu
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1PyzOE1
via IFTTT

Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer

Article

Acquisition of mesenchymal properties by cancer cells is a critical event for the development of malignancy. Here, the authors show that in renal cancer cells, lysosphosphatidic acid does not utilize the RhoA pathway but specifically activates the Arf6 mesenchymal pathway via its GPCRs and EFA6 to promote invasion, metastasis and drug resistance.

Nature Communications doi: 10.1038/ncomms10656

Authors: Shigeru Hashimoto, Shuji Mikami, Hirokazu Sugino, Ayumu Yoshikawa, Ari Hashimoto, Yasuhito Onodera, Shotaro Furukawa, Haruka Handa, Tsukasa Oikawa, Yasunori Okada, Mototsugu Oya, Hisataka Sabe

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1Xf6yr0
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/23U3ll2
via IFTTT

Single crystal functional oxides on silicon

Article

Synthesis of single-crystal complex-oxide films directly on silicon is difficult due to differing interfacial chemistry. Here, the authors demonstrate room-temperature integration of single-crystal lead zirconate titanate on to silicon to act as a gate insulator in a field-effect transistor.

Nature Communications doi: 10.1038/ncomms10547

Authors: Saidur Rahman Bakaul, Claudy Rayan Serrao, Michelle Lee, Chun Wing Yeung, Asis Sarker, Shang-Lin Hsu, Ajay Kumar Yadav, Liv Dedon, Long You, Asif Islam Khan, James David Clarkson, Chenming Hu, Ramamoorthy Ramesh, Sayeef Salahuddin

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1KCc3xU
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1KCcqsj
via IFTTT

Optogenetic control of nuclear protein export

Article

Light-inducible control of protein subcellular localization holds great promise for synthetic biology applications and insights into basic cell biology. Here the authors develop a genetically-encoded light-inducible nuclear export system and apply it to a synthetic repressor and p53 transcriptional activity.

Nature Communications doi: 10.1038/ncomms10624

Authors: Dominik Niopek, Pierre Wehler, Julia Roensch, Roland Eils, Barbara Di Ventura

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1Xf6x6h
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Xf6Z4z
via IFTTT

Artifacts Affecting Musculoskeletal Magnetic Resonance Imaging: Their Origins and Solutions

Publication date: Available online 8 February 2016
Source:Current Problems in Diagnostic Radiology
Author(s): Eira Roth, Michael Hoff, Michael L. Richardson, Alice S. Ha, Jack Porrino
Amongst articles within the radiology literature, few present the manifestations of magnetic resonance imaging artifacts (MRI) in a clinically-oriented manner. Recognizing such artifacts is imperative given the increasing clinical use of MRI and the emphasis by the American Board of Radiology on practical physics applications. The purpose of this article is to present magnetic resonance physics principles visually and conceptually in the context of common musculoskeletal radiology artifacts and their solutions, described using non-mathematical explanations.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1W8SD4r
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1KCctUY
via IFTTT

Three-Dimensional Quantitative Validation of Breast MRI Background Parenchymal Enhancement Assessments

Publication date: Available online 8 February 2016
Source:Current Problems in Diagnostic Radiology
Author(s): Richard Ha, Eralda Mema, Xiaotao Guo, Victoria Mango, Elise Desperito, Jason Ha, Ralph Wynn, Binsheng Zhao
IntroductionThe MRI background parenchymal enhancement (BPE) and its clinical significance as a bio-marker of breast cancer risk has been proposed based on qualitative studies. Previous BPE quantification studies lack appropriate correlation with BPE qualitative assessments. The purpose of this study is to validate our three-dimensional (3D) BPE quantification method with standardized BPE qualitative cases.MethodsAn IRB approved study reviewed 500 consecutive MRI cases (from 1/2013-12/2014) using a strict inclusion criteria and 120 cases that best represented each of the BPE qualitative categories (minimal/mild/moderate/marked) were selected. Blinded to the qualitative data, fibroglandular tissue (FGT) contours of pre-and post-contrast images were delineated using an in-house, proprietary segmentation algorithm. Metrics of BPE were calculated including % BPE [(ratio of BPE volume to FGT volume)x100] at multiple threshold levels to determine the optimal cut-off point for BPE quantification that best correlated with the reference BPE qualitative cases.ResultsThe highest positive correlation was present at 1.5x pre-SI threshold level (r=0.84, p <0.001). At this level, the BPE qualitative assessment of minimal, mild, moderate and marked correlated with the mean quantitative % BPE of 14.1%(95%CI, 10.9-17.2), 26.1%(22.8-29.3), 45.9%(40.2-51.7) and 74.0%(68.6-79.5) respectively. A one-way ANOVA with post-hoc analysis showed that at 1.5x pre-SI level, the quantitative % BPE measurements best differentiated the four reference BPE qualitative groups [F(3,117)=106.8, p<0.001].ConclusionOur 3D BPE quantification methodology was validated using the reference BPE qualitative cases and could become an invaluable clinical tool to more accurately assess breast cancer risk and to test chemoprevention strategies.

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1ScyMTP
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Xf6XJV
via IFTTT

Evaluation of Speech Amplification Devices in Parkinson’s Disease.

Conclusions: This study found preliminary evidence of improved speech performance with device use for individuals with PD. A tentative hierarchy is suggested for device recommendations. Future research is needed to determine which measures will predict long-term device acceptance in PD. PMID: 26847491 [PubMed – as supplied by publisher] (Source: American Journal of Speech-Language Pathology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1ScHIsc
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1KCctUW
via IFTTT

Mechanical evidence that Australopithecus sediba was limited in its ability to eat hard foods

Article

Dietary adaptations of extinct early humans are often inferred from dental microwear data. Here, the authors employ mechanical analyses to show that Australopithecus sediba had limited ability to consume hard foods.

Nature Communications doi: 10.1038/ncomms10596

Authors: Justin A. Ledogar, Amanda L. Smith, Stefano Benazzi, Gerhard W. Weber, Mark A. Spencer, Keely B. Carlson, Kieran P. McNulty, Paul C. Dechow, Ian R. Grosse, Callum F. Ross, Brian G. Richmond, Barth W. Wright, Qian Wang, Craig Byron, Kristian J. Carlson, Darryl J. de Ruiter, Lee R. Berger, Kelli Tamvada, Leslie C. Pryor, Michael A. Berthaume, David S. Strait

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1KCc3ho
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Xf6XJR
via IFTTT

Description and Evaluation of a Home-Based, Parent-Administered Program for Teaching Enhanced Natural Gestures to Individuals With Angelman Syndrome.

Conclusions: ENGs may, in conjunction with other forms of augmentative and alternative communication, represent a viable method of communication for many individuals with Angelman syndrome. Further research is warranted to explore the feasibility of ENGs with other populations of individuals with severe disabilities and complex communication challenges. PMID: 26847597 [PubMed – as supplied by publisher] (Source: American Journal of Speech-Language Pathology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1UZUSa1
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1KCctUU
via IFTTT

Shaping metallic glasses by electromagnetic pulsing

Article

Metallic glasses can be softened to different shapes whilst maintaining mechanical properties, and the related thermoplastic processing requires a heating source and an applied force. Here, the authors show an effective thermoplastic approach by a coupling between electric pulses and a magnetic field.

Nature Communications doi: 10.1038/ncomms10576

Authors: Georg Kaltenboeck, Marios D. Demetriou, Scott Roberts, William L. Johnson

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1KCc6tG
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Xf6Z4x
via IFTTT

Sound Production Treatment: Synthesis and Quantification of Outcomes

Conclusion These benchmarks may assist in evaluating the effects of interventions for individuals with AOS utilizing similar outcome measures in both clinical and research settings. (Source: American Journal of Speech-Language Pathology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1nUhsWH
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1KCctUR
via IFTTT

Relationships Between Formant Frequencies of Sustained Vowels and Tongue Contours Measured by Ultrasonography

Conclusions Ultrasonographic measurements of tongue contour correlated well to the formant frequencies. The results stressed the importance of tongue shaping in articulation. Although more studies are necessary in clinical implications, disorders associated with abnormal tongue shaping may be the target applications in the future. (Source: American Journal of Speech-Language Pathology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1Q633n5
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Xf6XJM
via IFTTT

Using Spoken Language Benchmarks to Characterize the Expressive Language Skills of Young Children With Autism Spectrum Disorders

Conclusion The spoken language benchmarks are useful for characterizing early communication profiles and investigating features that influence expressive language growth. (Source: American Journal of Speech-Language Pathology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1nUdOfj
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1KCcqsd
via IFTTT

Editor’s Perspective: Supplements and Forums

Purpose In this article, the Editor of the American Journal of Speech-Language Pathology reflects on the distinction between the Clinical or Research Forum and the Supplement—and the important contributions that each dissemination format makes. (Source: American Journal of Speech-Language Pathology)

from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1Q631eW
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/23U3l4G
via IFTTT

The effect of upper limb casting on gait pattern.

Casting of the arm may interfere with normal walking patterns because of additional load of the cast or prevention of arm swing. This study aimed to determine the effect of applying various casts on temporospatial walking parameters, including gait velocity and cadence, step length, and single limb support. A computerized gait system was used to assess these variables for 23 healthy individuals in four walking modes: normal walking, with a cast above the elbow and a sling, and with a cast below the elbow, with and without a sling. Thirteen participants had their dominant hand casted and 10 had their nondominant hand casted. On average, casted participants took significantly smaller steps with the leg on the casted side and spent less time supported on the casted side. The least changes were noted with the arm in a cast below the elbow and no sling, and the greatest changes were noted with the arm in a cast above the elbow and in a sling. This difference was heightened when the dominant hand was casted and lessened when the nondominant hand was casted. No differences were found in walking velocity or cadence between the walking modes. Casting of the upper limb has significant effects on gait, which should be taken into consideration, especially in individuals with previous gait abnormalities. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1Q6dpTY
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1PyzOnw
via IFTTT

A Leukocyte Immune-Type Receptor Subset Is a Marker of Antiviral Cytotoxic Cells in Channel Catfish, Ictalurus punctatus INFECTIOUS DISEASE AND HOST RESPONSE

Channel catfish, Ictalurus punctatus, leukocyte immune type receptors (LITRs) represent a multigene family that encodes Ig superfamily proteins that mediate activating or inhibitory signaling. In this study, we demonstrate the use of mAb CC41 to monitor viral cytotoxic responses in catfish and determine that CC41 binds to a subset of LITRs on the surface of catfish clonal CTLs. Homozygous gynogenetic catfish were immunized with channel catfish virus (CCV)–infected MHC-matched clonal T cells (G14D-CCV), and PBL were collected at various times after immunization for flow cytometric analyses. The percentage of CC41+ cells was significantly increased 5 d after primary immunization with G14D-CCV and at 3 d after a booster immunization as compared with control fish only injected with G14D. Moreover, CC41+ cells magnetically isolated from the PBL specifically killed CCV-infected targets as measured by 51Cr release assays and expressed messages for CD3, perforin, and at least one of the CD4-like receptors as analyzed by RNA flow cytometry. When MLC effector cells derived from a G14D-CCV–immunized fish were preincubated with CC41 mAb, killing of G14D-CCV targets was reduced by ~40%, suggesting that at least some LITRs have a role in target cell recognition and/or cytotoxicity. The availability of a LITR-specific mAb has allowed, to our knowledge for the first time, functional characterization of LITRs in an autologous system. In addition, the identification of an LITR subset as a cytotoxic cell marker will allow for more effective monitoring of catfish immune responses to pathogens.

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1PyuP6d
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/23U3l4E
via IFTTT

Highly Accurate Sequencing of Full-Length Immune Repertoire Amplicons Using Tn5-Enabled and Molecular Identifier-Guided Amplicon Assembly NOVEL IMMUNOLOGICAL METHODS

Ab repertoire sequencing is a powerful tool to analyze the adaptive immune system. To sequence entire Ab repertoires, amplicons are created from Ab H chain (IgH) transcripts and sequenced on a high-throughput sequencer. The field of immune repertoire sequencing is growing rapidly and the protocols used are steadily improving; however, thus far, immune repertoire sequencing protocols have not been able to sequence full-length immune repertoires including the entire IgH V region and enough of the IgH C region to identify isotype subtypes. In this study, we present a method that combines Tn5 transposase and molecular identifiers for the highly accurate sequencing of amplicons >500 bp using Illumina short read paired-end sequencing. We then apply this method to Ab H chain amplicons to sequence the first, to our knowledge, highly accurate full-length immune repertoire.

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1PyuOPL
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1PyzOnr
via IFTTT

Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis IMMUNOTHERAPY AND VACCINES

Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1–20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8–14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor–targeted therapies.

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1TPoecL
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/23U3mWi
via IFTTT

IL-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts TRANSPLANTATION

Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil, and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor (IL-1R) signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared with complete MHC-mismatched wild-type cardiac allografts, IL-1R–/– allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant, whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL-1R–/– allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-–producing cells. CD8 T cell–mediated rejection of IL-1R–/– cardiac allografts took 3 wk longer than wild-type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL-1R–/–/wild-type chimeric donors indicated that IL-1R signaling on graft nonhematopoietic-derived, but not bone marrow–derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild-type allografts. These studies implicate IL-1R–mediated signals by allograft parenchymal cells in generating the stimuli-provoking development and elicitation of optimal alloimmune responses to the grafts.

from #Medicine-Sfakianakis via simeraentaxei on Inoreader http://ift.tt/1PyuNeu
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1ScVxqH
via IFTTT

On hidden Z-matrices and the linear complementarity problem

Publication date: 1 May 2016
Source:Linear Algebra and its Applications, Volume 496
Author(s): Dipti Dubey, S.K. Neogy
In this paper, we explore various matrix-theoretic aspects of the hidden Z class and demonstrate how the concept of principal pivot transform can be effectively used to extend many existing results. In fact, we revisit various results obtained for hidden Z class by Mangasarian, Cottle and Pang in context of solving linear complementarity problems as linear programs. We identify hidden Z-matrices of special category and discuss the number of solutions of the associated linear complementarity problems. We also present game theoretic interpretation of various results related to hidden Z class and obtain proofs following the game theoretic approach of Raghavan for a subclass of Z-matrices.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1SEMn6U
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nYPKZm
via IFTTT

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme)

Abstract

Background

Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy.

Methods/Design

OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80 % statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [¹⁸F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project.

Discussion

Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response.

EudraCT Number: 2011-004997-27

Trial registration

ClinicalTrials.gove number, NCT01718873

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/20Gipni
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1T1fyiW
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/20RU3Um
via IFTTT

Optimal regimen of trastuzumab in combination with oxaliplatin/ capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial

Abstract

Background

The ToGA study showed that trastuzumab plus chemotherapy prolonged median survival in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Among chemotherapy options, oxaliplatin might be as effective as cisplatin but has shown to be more tolerable. To further improve treatment options for patients with advanced gastric cancer, we initiated a study to evaluate the efficacy and safety of trastuzumab plus oxaliplatin/capecitabine in patients with HER2-positive advanced gastric cancer.

Methods

CGOG1001 was an open-label, multicenter, prospective phase II study. Patients with chemotherapy-naive HER2-positive advanced gastric cancer were eligible. Trastuzumab was administered at a loading dose of 8 mg/kg followed by 6 mg/kg infusion every 3 weeks (q3w). Oxaliplatin was administrated as a 130 mg/m2 infusion, q3w, for up to 6 cycles. Capecitabine 1000 mg/m2 was given orally twice daily on days 1–14 followed by a 7-day rest interval. Trastuzumab and capecitabine were continued until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Simon two-stage design (H0 = 40 %, H1 = 60 %, α = 0.05, β = 0.2) by Response Evaluation Criteria In Solid Tumors 1.0 was applied.

Results

Fifty-one patients were enrolled. Confirmed response was recorded in 46 patients. One patient achieved complete response and 33 patients achieved partial response (response rate 34/51 [66.7 %] in the intent-to-treat population). Median follow-up time was 28.6 months, with a median progression-free survival of 9.2 months (95 % confidence interval [CI]: 6.5–11.6) and a median overall survival (OS) of 19.5 months (95 % CI: 15.5–26.0). Patients with a HER2/CEP17 ratio of greater than five achieved improved OS (20.9 vs 19.5 months, p = 0.001). The most common adverse events of grade 3 or above were thrombocytopenia (21.6 %), neutropenia (13.7 %), anemia (5.9 %) and leucopenia (3.9 %).

Conclusion

The addition of trastuzumab to oxaliplatin/capecitabine was well tolerated and the results demonstrated encouraging efficacy.

Trial registration

ClinicalTrials.gov NCT01364493.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1XepbLJ
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1mof6hP
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nYPKJ8
via IFTTT

The generation of all rational orthogonal matrices in Rp,q

Publication date: 1 May 2016
Source:Linear Algebra and its Applications, Volume 496
Author(s): M.A. Rodríguez-Andrade, G. Aragón-González, J.L. Aragón
A method for generating all rational generalized matrices on indefinite real inner product spaces isomorphic to Rp,q is presented. The proposed method is based on the proof of a weak version of the Cartan–Dieudonné theorem, handled using Clifford algebras. It is shown that all rational B-orthogonal matrices in an indefinite inner product space (X,B) are products of simple matrices with rational entries.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1nTNXnQ
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nYPKJ6
via IFTTT

Evaluation of TgH(CX3CR1-EGFP) mice implanted with mCherry-GL261 cells as an in vivo model for morphometrical analysis of glioma-microglia interaction

Abstract

Background

Glioblastoma multiforme is the most aggressive brain tumor. Microglia are prominent cells within glioma tissue and play important roles in tumor biology. This work presents an animal model designed for the study of microglial cell morphology in situ during gliomagenesis. It also allows a quantitative morphometrical analysis of microglial cells during their activation by glioma cells.

Methods

The animal model associates the following cell types: 1- mCherry red fluorescent GL261 glioma cells and; 2- EGFP fluorescent microglia, present in the TgH(CX3CR1-EGFP) mouse line. First, mCherry-GL261 glioma cells were implanted in the brain cortex of TgH(CX3CR1-EGFP) mice. Epifluorescence − and confocal laser-scanning microscopy were employed for analysis of fixed tissue sections, whereas two-photon laser-scanning microscopy (2P-LSM) was used to track tumor cells and microglia in the brain of living animals.

Results

Implanted mCherry-GL261 cells successfully developed brain tumors. They mimic the aggressive behavior found in human disease, with a rapid increase in size and the presence of secondary tumors apart from the injection site. As tumor grows, mCherry-GL261 cells progressively lost their original shape, adopting a heterogeneous and diffuse morphology at 14–18 d. Soma size increased from 10–52 μm. At this point, we focused on the kinetics of microglial access to glioma tissues. 2P-LSM revealed an intense microgliosis in brain areas already shortly after tumor implantation, i.e. at 30 min. By confocal microscopy, we found clusters of microglial cells around the tumor mass in the first 3 days. Then cells infiltrated the tumor area, where they remained during all the time points studied, from 6–18 days. Microglia in contact with glioma cells also present changes in cell morphology, from a ramified to an amoeboid shape. Cell bodies enlarged from 366 ± 0.0 μm2, in quiescent microglia, to 1310 ± 146.0 μm2, and the cell processes became shortened.

Conclusions

The GL261/CX3CR1 mouse model reported here is a valuable tool for imaging of microglial cells during glioma growth, either in fixed tissue sections or living animals. Remarkable advantages are the use of immunocompetent animals and the simplified imaging method without the need of immunohistochemical procedures.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1Xep8Q0
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1T1fyiS
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/20RU62g
via IFTTT

On the Choi–Lam analogue of Hilbert’s 1888 theorem for symmetric forms

Publication date: 1 May 2016
Source:Linear Algebra and its Applications, Volume 496
Author(s): Charu Goel, Salma Kuhlmann, Bruce Reznick
A famous theorem of Hilbert from 1888 states that for given n and d, every positive semidefinite (psd) real form of degree 2d in n variables is a sum of squares (sos) of real forms if and only if n=2 or d=1 or (n,2d)=(3,4). In 1976, Choi and Lam proved the analogue of Hilbert's Theorem for symmetric forms by assuming the existence of psd not sos symmetric n-ary quartics for n≥5. In this paper we complete their proof by constructing explicit psd not sos symmetric n-ary quartics for n≥5.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1SEMkYL
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nYPI3L
via IFTTT

Computerized tomography angiography in preoperative assessment of intravenous leiomyomatosis extending to inferior vena cava and heart

Abstract

Background

Intravenous leiomyomatosis (IVL) extending to inferior vena cava and heart is one of the most challenging conditions for surgical treatment. We explored the use of computerized tomography angiography (CTA) in preoperative assessment for this disease.

Methods

A cohort of 31 patients with IVL extending to inferior vena cava and heart were reviewed from the year 2002 to 2014, focusing on the preoperative CTA imaging characteristics and the surgical procedures in clinical treatment.

Results

All patients were diagnosed correctly combining the clinical medical history and CTA imaging. Thirteen patients had tumors confined within the inferior vena cava, and 18 patients had tumors intruding into the right heart. Furthermore, 15 tumors were located in the right atrium alone, and 3 tumors involved both the right atrium and the right ventricle. All patients had simple or multiple soft tissue masses from the pelvis, with 22 tumors extending into inferior vena cava through the iliac veins and 9 tumors through the ovarian veins. Three patients had tumors invading into lung and underwent tumor thrombus resection in the pulmonary artery. Patients received either one-stage surgery or two-stage surgery dependent on patient general condition and tumor status. All operations were successfully performed by multidisciplinary cooperation, including gynecology, cardiac surgery, and vascular surgery, without severe surgical-related complications or deaths.

Conclusions

CTA imaging can present location, size, and full-scale extension pathway of IVL lesions, and can be used as first-line imaging technique in preoperative assessment, having great significance in making surgical plan and obtaining successful outcome.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1XepaHB
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1mof3m3
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/20RU62k
via IFTTT

Eigenschemes and the Jordan canonical form

Publication date: 1 May 2016
Source:Linear Algebra and its Applications, Volume 496
Author(s): Hirotachi Abo, David Eklund, Thomas Kahle, Chris Peterson
We study the eigenscheme of a matrix which encodes information about the eigenvectors and generalized eigenvectors of a square matrix. The two main results in this paper are a decomposition of the eigenscheme of a matrix into primary components and the fact that this decomposition encodes the numeric data of the Jordan canonical form of the matrix. We also describe how the eigenscheme can be interpreted as the zero locus of a global section of the tangent bundle on projective space. This interpretation allows one to see eigenvectors and generalized eigenvectors of matrices from an alternative viewpoint.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1nTNUs8
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/20RU5M2
via IFTTT

The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma—differences in histological subtypes

Abstract

Background

Extensive research has increased our understanding of the molecular alterations needed for non-small cell lung cancer (NSCLC) development. Deregulation of a pathway including MYCN, HMGA2 and CDKN2A, with the participation of DICER1, is of importance in several solid tumours, and may also be of significance in the pathogenesis of NSCLC.

Methods

Gene expression of MYCN, HMGA2, CDKN2A and DICER1 were investigated with RT-qPCR in surgically resected NSCLC tumour tissue from 175 patients. Expression of the let-7 microRNA family was performed in 78 adenocarcinomas and 16 matching normal lung tissue samples using microarrays. The protein levels of HMGA2 were determined by immunohistochemistry in 156 tumour samples and the protein expression was correlated with gene expression. Associations between clinical data, including time to recurrence, and expression of mRNA, protein and microRNAs were analysed.

Results

Compared to adenocarcinomas, squamous cell carcinomas had a median 5-fold increase in mRNA expression of HMGA2 (p = 0.003). A positive correlation (r = 0.513, p < 0.010) between HMGA2 mRNA expression and HMGA2 protein expression was seen. At the protein level, 90 % of the squamous cell carcinomas expressed high levels of the HMGA2 protein compared to 47 % of the adenocarcinomas (p < 0.0001). MYCN was positively correlated with HMGA2 (p < 0.010) and DICER1 mRNA expression (p < 0.010), and the expression of the let-7 microRNAs seemed to be correlated with the genes studied. MYCN expression was associated with time to recurrence in multivariate survival analyses (p = 0.020).

Conclusions

A significant difference in HMGA2 mRNA expression between the histological subtypes of NSCLC was seen with a higher expression in the squamous cell carcinomas. This was also found at the protein level, and we found a good correlation between the mRNA and the protein expression of HMGA2. Moreover, the expression of MYCN, HMGA2, and DICER1 seems to be correlated to each other and the expression of the let7-genes impacted by their expression. MYCN gene expression seems to be of importance in time to recurrence in this patient cohort with resected NSCLC.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/20Giojg
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1T1fyiN
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/20RU62s
via IFTTT

On Lipschitz analysis and Lipschitz synthesis for the phase retrieval problem

Publication date: 1 May 2016
Source:Linear Algebra and its Applications, Volume 496
Author(s): Radu Balan, Dongmian Zou
We prove two results with regard to reconstruction from magnitudes of frame coefficients (the so called "phase retrieval problem"). First we show that phase retrievable nonlinear maps are bi-Lipschitz with respect to appropriate metrics on the quotient space. Specifically, if nonlinear analysis maps α,β:Hˆ→Rm are injective, with α(x)=(|〈x,fk〉|)k=1m and β(x)=(|〈x,fk〉|2)k=1m, where {f1,…,fm} is a frame for a Hilbert space H and Hˆ=H/T1, then α is bi-Lipschitz with respect to the class of "natural metrics" Dp(x,y)=minφ⁡‖x−eiφy‖p, whereas β is bi-Lipschitz with respect to the class of matrix-norm induced metrics dp(x,y)=‖xx⁎−yy⁎‖p. Second we prove that reconstruction can be performed using Lipschitz continuous maps. That is, there exist left inverse maps (synthesis maps) ω,ψ:Rm→Hˆ of α and β respectively, that are Lipschitz continuous with respect to appropriate metrics. Additionally, we obtain the Lipschitz constants of ω and ψ in terms of the lower Lipschitz constants of α and β, respectively. Surprisingly, the increase in both Lipschitz constants is a relatively small factor, independent of the space dimension or the frame redundancy.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1SEMmQl
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1nYPI3P
via IFTTT

Editorial_Board

from #ORL-AlexandrosSfakianakis via simeraentaxei on Inoreader http://ift.tt/1oma8DL
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1TOS6WT
via IFTTT

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme)

Abstract

Background

Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy.

Methods/Design

OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80 % statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [¹⁸F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project.

Discussion

Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response.

EudraCT Number: 2011-004997-27

Trial registration

ClinicalTrials.gove number, NCT01718873

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/20Gipni
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RjA0LY
via IFTTT

Optimal regimen of trastuzumab in combination with oxaliplatin/ capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial

Abstract

Background

The ToGA study showed that trastuzumab plus chemotherapy prolonged median survival in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Among chemotherapy options, oxaliplatin might be as effective as cisplatin but has shown to be more tolerable. To further improve treatment options for patients with advanced gastric cancer, we initiated a study to evaluate the efficacy and safety of trastuzumab plus oxaliplatin/capecitabine in patients with HER2-positive advanced gastric cancer.

Methods

CGOG1001 was an open-label, multicenter, prospective phase II study. Patients with chemotherapy-naive HER2-positive advanced gastric cancer were eligible. Trastuzumab was administered at a loading dose of 8 mg/kg followed by 6 mg/kg infusion every 3 weeks (q3w). Oxaliplatin was administrated as a 130 mg/m2 infusion, q3w, for up to 6 cycles. Capecitabine 1000 mg/m2 was given orally twice daily on days 1–14 followed by a 7-day rest interval. Trastuzumab and capecitabine were continued until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Simon two-stage design (H0 = 40 %, H1 = 60 %, α = 0.05, β = 0.2) by Response Evaluation Criteria In Solid Tumors 1.0 was applied.

Results

Fifty-one patients were enrolled. Confirmed response was recorded in 46 patients. One patient achieved complete response and 33 patients achieved partial response (response rate 34/51 [66.7 %] in the intent-to-treat population). Median follow-up time was 28.6 months, with a median progression-free survival of 9.2 months (95 % confidence interval [CI]: 6.5–11.6) and a median overall survival (OS) of 19.5 months (95 % CI: 15.5–26.0). Patients with a HER2/CEP17 ratio of greater than five achieved improved OS (20.9 vs 19.5 months, p = 0.001). The most common adverse events of grade 3 or above were thrombocytopenia (21.6 %), neutropenia (13.7 %), anemia (5.9 %) and leucopenia (3.9 %).

Conclusion

The addition of trastuzumab to oxaliplatin/capecitabine was well tolerated and the results demonstrated encouraging efficacy.

Trial registration

ClinicalTrials.gov NCT01364493.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/1XepbLJ
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Xephmo
via IFTTT

Computerized tomography angiography in preoperative assessment of intravenous leiomyomatosis extending to inferior vena cava and heart

Abstract

Background

Intravenous leiomyomatosis (IVL) extending to inferior vena cava and heart is one of the most challenging conditions for surgical treatment. We explored the use of computerized tomography angiography (CTA) in preoperative assessment for this disease.

Methods

A cohort of 31 patients with IVL extending to inferior vena cava and heart were reviewed from the year 2002 to 2014, focusing on the preoperative CTA imaging characteristics and the surgical procedures in clinical treatment.

Results

All patients were diagnosed correctly combining the clinical medical history and CTA imaging. Thirteen patients had tumors confined within the inferior vena cava, and 18 patients had tumors intruding into the right heart. Furthermore, 15 tumors were located in the right atrium alone, and 3 tumors involved both the right atrium and the right ventricle. All patients had simple or multiple soft tissue masses from the pelvis, with 22 tumors extending into inferior vena cava through the iliac veins and 9 tumors through the ovarian veins. Three patients had tumors invading into lung and underwent tumor thrombus resection in the pulmonary artery. Patients received either one-stage surgery or two-stage surgery dependent on patient general condition and tumor status. All operations were successfully performed by multidisciplinary cooperation, including gynecology, cardiac surgery, and vascular surgery, without severe surgical-related complications or deaths.

Conclusions

CTA imaging can present location, size, and full-scale extension pathway of IVL lesions, and can be used as first-line imaging technique in preoperative assessment, having great significance in making surgical plan and obtaining successful outcome.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/1XepaHB
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Lcfzds
via IFTTT

Evaluation of TgH(CX3CR1-EGFP) mice implanted with mCherry-GL261 cells as an in vivo model for morphometrical analysis of glioma-microglia interaction

Abstract

Background

Glioblastoma multiforme is the most aggressive brain tumor. Microglia are prominent cells within glioma tissue and play important roles in tumor biology. This work presents an animal model designed for the study of microglial cell morphology in situ during gliomagenesis. It also allows a quantitative morphometrical analysis of microglial cells during their activation by glioma cells.

Methods

The animal model associates the following cell types: 1- mCherry red fluorescent GL261 glioma cells and; 2- EGFP fluorescent microglia, present in the TgH(CX3CR1-EGFP) mouse line. First, mCherry-GL261 glioma cells were implanted in the brain cortex of TgH(CX3CR1-EGFP) mice. Epifluorescence − and confocal laser-scanning microscopy were employed for analysis of fixed tissue sections, whereas two-photon laser-scanning microscopy (2P-LSM) was used to track tumor cells and microglia in the brain of living animals.

Results

Implanted mCherry-GL261 cells successfully developed brain tumors. They mimic the aggressive behavior found in human disease, with a rapid increase in size and the presence of secondary tumors apart from the injection site. As tumor grows, mCherry-GL261 cells progressively lost their original shape, adopting a heterogeneous and diffuse morphology at 14–18 d. Soma size increased from 10–52 μm. At this point, we focused on the kinetics of microglial access to glioma tissues. 2P-LSM revealed an intense microgliosis in brain areas already shortly after tumor implantation, i.e. at 30 min. By confocal microscopy, we found clusters of microglial cells around the tumor mass in the first 3 days. Then cells infiltrated the tumor area, where they remained during all the time points studied, from 6–18 days. Microglia in contact with glioma cells also present changes in cell morphology, from a ramified to an amoeboid shape. Cell bodies enlarged from 366 ± 0.0 μm2, in quiescent microglia, to 1310 ± 146.0 μm2, and the cell processes became shortened.

Conclusions

The GL261/CX3CR1 mouse model reported here is a valuable tool for imaging of microglial cells during glioma growth, either in fixed tissue sections or living animals. Remarkable advantages are the use of immunocompetent animals and the simplified imaging method without the need of immunohistochemical procedures.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/1Xep8Q0
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1XepgyQ
via IFTTT

The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma—differences in histological subtypes

Abstract

Background

Extensive research has increased our understanding of the molecular alterations needed for non-small cell lung cancer (NSCLC) development. Deregulation of a pathway including MYCN, HMGA2 and CDKN2A, with the participation of DICER1, is of importance in several solid tumours, and may also be of significance in the pathogenesis of NSCLC.

Methods

Gene expression of MYCN, HMGA2, CDKN2A and DICER1 were investigated with RT-qPCR in surgically resected NSCLC tumour tissue from 175 patients. Expression of the let-7 microRNA family was performed in 78 adenocarcinomas and 16 matching normal lung tissue samples using microarrays. The protein levels of HMGA2 were determined by immunohistochemistry in 156 tumour samples and the protein expression was correlated with gene expression. Associations between clinical data, including time to recurrence, and expression of mRNA, protein and microRNAs were analysed.

Results

Compared to adenocarcinomas, squamous cell carcinomas had a median 5-fold increase in mRNA expression of HMGA2 (p = 0.003). A positive correlation (r = 0.513, p < 0.010) between HMGA2 mRNA expression and HMGA2 protein expression was seen. At the protein level, 90 % of the squamous cell carcinomas expressed high levels of the HMGA2 protein compared to 47 % of the adenocarcinomas (p < 0.0001). MYCN was positively correlated with HMGA2 (p < 0.010) and DICER1 mRNA expression (p < 0.010), and the expression of the let-7 microRNAs seemed to be correlated with the genes studied. MYCN expression was associated with time to recurrence in multivariate survival analyses (p = 0.020).

Conclusions

A significant difference in HMGA2 mRNA expression between the histological subtypes of NSCLC was seen with a higher expression in the squamous cell carcinomas. This was also found at the protein level, and we found a good correlation between the mRNA and the protein expression of HMGA2. Moreover, the expression of MYCN, HMGA2, and DICER1 seems to be correlated to each other and the expression of the let7-genes impacted by their expression. MYCN gene expression seems to be of importance in time to recurrence in this patient cohort with resected NSCLC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/20Giojg
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RjA26p
via IFTTT

Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck

Abstract

Background

FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).

Method

In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.

Results

The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95 % CI, 1.1–5.8, P = 0.043 and aHR, 2.7; 95 % CI, 1.2–6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95 % CI, 1.2–5.7 and 1.1–3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95 % CI, 1.1–5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.

Conclusion

These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/20Gil7d
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1XepgyN
via IFTTT

FDG PET/CT as a prognostic biomarker in the era of molecular-targeting therapies: max SUVmax predicts survival of patients with advanced renal cell carcinoma

Abstract

Background

Various molecular-targeting therapies have become available for the treatment of advanced renal cell carcinoma (RCC). Accurate prognostication is desirable for choosing the appropriate treatment for individual patients. 18F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is a non-invasive tool for evaluating glucose accumulation, which can be an index of biological characteristics of cancer. We prospectively evaluated FDG PET/CT as a prognostic indicator in patients with advanced RCC.

Methods

A total of 101 patients slated for different systematic therapies for advanced RCC were enrolled between 2008 and 2014. A total of 61 patients had recurrent RCC (58 metastatic and 3 regional) and 40 patients had stage IV RCC (36 metastatic and 4 locoregional). Sixteen patients had not undergone nephrectomy. Pre-treatment FDG PET/CT was performed, and the max SUVmax (the highest SUV measurement in each patient) was recorded. The max SUVmax was compared with different clinical risk factors as prognostic indicators. The median observation period was 18 months (range 1–70 months).

Results

The max SUVmax of the 101 subjects ranged from undetectable to 23.0 (median 6.9). Patients with high max SUVmax had a poor prognosis. Multivariate analysis with standard risk factors revealed that max SUVmax was an independent predictor of survival (p < 0.001; hazard ratio 1.265; 95 % confidence interval 1.159–1.380). A cutoff of 8.8 for max SUVmax advocated in our previous report was highly significant (p < 0.0001). When we subclassified the max SUVmax values, the median overall survival of subjects with max SUVmax < 7.0 was 41.9 months. That of subjects with max SUVmax between 7.0 and 12.0 was 20.6 months. That of subjects with max SUVmax ≥ 12.0 was 4.2 months. The differences were statistically significant.

Conclusions

Pretreatment max SUVmax assessed by FDG PET/CT is a useful prognostic marker for patients with advanced RCC, providing helpful information for clinical decision making.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/1Xep8iQ
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RjA0vp
via IFTTT

Ustekinumab in Pediatric Crohn’s Disease Patients: Case Review.

Objectives: We describe the use of ustekinumab for four patients with pediatric Crohn's disease treated at the Seattle Children's Hospital Inflammatory Bowel Disease Center. Methods: A retrospective chart review was done to identify patients' clinical data, disease phenotype, treatment history, and laboratory and growth parameters before treatment with ustekinumab and at last follow up. Adverse events while on ustekinumab were also recorded. Results: Four adolescent patients with Crohn's disease at our center received Ustekinumab. All had previously received corticosteroids, methotrexate, azathioprine/6-mercaptopurine, and both infliximab and adalimumab. Patients had varying disease phenotypes. Ages at ustekinumab initiation were 12, 13, 16, and 17. Weight ranged from 40.5 kg to 57.8 kg, mean 49.5 kg. Two patients showed clinical response and remain on ustekinumab. Two patients discontinued therapy due to continued symptoms and disease complications and required multiple hospitalizations. Conclusions: Ustekinumab was used in four children with pediatric Crohn's disease with two of four patients showing clinical response (one with persistently elevated CRP). A prospective study is needed to define its efficacy, safety, and placement in managing pediatric Crohn's disease in the future. (C) 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/20GinvM
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Xeph60
via IFTTT

Have We Reached the Limits with Regard to Amino Acid/Protein Intakes in Preterm Infants?.

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/1Xep82f
via IFTTT Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RjA0f0
via IFTTT