Robust Reconstitution of Tuberculosis-Specific Polyfunctional CD4+ T-Cell Responses and Rising Systemic Interleukin 6 in Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

Background. The immunopathogenesis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains unclear. We determined the association between pathogen-specific T-cell responses and development of paradoxical TB-IRIS on antiretroviral therapy (ART).

Methods. This study was nested within a prospective cohort study of HIV-infected patients with active pulmonary tuberculosis and baseline CD4 counts ≤125 cells/µL initiating ART. T-cell immune activation (CD38, HLA-DR, and PD-1 expression), phenotype, and polyfunctional pathogen-specific cellular immune responses prior to and 4 weeks after ART initiation were determined by flow cytometry. Patients with TB-IRIS were compared to non-IRIS controls using 2 and rank-sum tests and logistic regression.

Results. TB-IRIS patients and controls had similar CD4 counts, levels of T-cell–associated immune activation, frequencies of T-cell memory subsets, and frequencies of interferon gamma (IFN-+)/interleukin 2 (IL-2+)/tumor necrosis factor alpha (TNF-α+) CD4+ T-cells prior to ART initiation. After ART initiation, cellular immune activation and T-cell subsets also were similar in TB-IRIS patients and controls. In contrast, TB-IRIS patients had significantly greater early increases in the frequency of tuberculosis-specific polyfunctional IFN-+/IL-2+/TNF-α+ CD4+ T-cells on ART (P = .02); each quartile increase in the percentage of these cells was independently associated with a 2.8-fold increased risk of TB-IRIS (95% confidence interval, 1.1 to 7.5-fold). In a secondary analysis, patients with TB-IRIS had rapid, concomitant increases in tuberculosis-specific adaptive immune responses and interleukin 6 (IL-6) levels, whereas controls with similarly rapid increases in cellular immune function had IL-6 levels that tended to decrease on ART.

Conclusions. Rapid expansion of tuberculosis-specific polyfunctional CD4+ T-cell responses, likely linked to increases in IL-6, is associated with development of paradoxical TB-IRIS.

from #Infections via alexandrossfakianakis on Inoreader http://ift.tt/1LT4VbI
via IFTTT

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1ON9WCD
via IFTTT

New Diagnostic Techniques Highlight the Need for Negative Controls

from #Infections via alexandrossfakianakis on Inoreader http://ift.tt/1QqsGxa
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1oNj1pG
via IFTTT

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

Editorial Commentary: Stemming the Tide: Can New Approaches to HIV Treatment Reverse the Trend of Rising Drug Prices in the United States?

from #Infections via alexandrossfakianakis on Inoreader http://ift.tt/1QqsGgQ
via IFTTT

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1ON9WCv
via IFTTT

The Emergence of Zoonotic Onchocerca lupi Infection in the United States – A Case-Series

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies.

from #Infections via alexandrossfakianakis on Inoreader http://ift.tt/1LT4UVj
via IFTTT

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

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

Hemophagocytic Lymphohistiocytosis Associated With Bartonella henselae Infection in an HIV-Infected Patient

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome that often occurs in immunocompromised patients. We report the first case of HLH due to Bartonella henselae infection in a patient with human immunodeficiency virus infection. Early recognition of HLH and B. henselae through liver biopsy and serological tests led to the patient's recovery.

from #Infections via alexandrossfakianakis on Inoreader http://ift.tt/1TP75iY
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1L3FiKt
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1ON9Z1b
via IFTTT

Methylprednisolone blocks interleukin 1 beta induced calcitonin gene related peptide release in trigeminal ganglia cells

Methylprednisolone (MPD) is a rapid acting highly effective cluster headache preventive and also suppresses the recurrence of migraine attacks. Previously, we could demonstrate that elevated CGRP plasma levels…

from #Neuroscience via alexandrossfakianakis on Inoreader http://ift.tt/1XYM8CR
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1L3FiKp
via IFTTT

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

A 55-Year-Old French Man With Sudden Hemiparesis and Hemiplegia

from #Infections via alexandrossfakianakis on Inoreader http://ift.tt/1QqsEFI
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1TlOY5X
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1ON9Wme
via IFTTT

Input estimation for drug discovery using optimal control and Markov chain Monte Carlo approaches

Abstract

Input estimation is employed in cases where it is desirable to recover the form of an input function which cannot be directly observed and for which there is no model for the generating process. In pharmacokinetic and pharmacodynamic modelling, input estimation in linear systems (deconvolution) is well established, while the nonlinear case is largely unexplored. In this paper, a rigorous definition of the input-estimation problem is given, and the choices involved in terms of modelling assumptions and estimation algorithms are discussed. In particular, the paper covers Maximum a Posteriori estimates using techniques from optimal control theory, and full Bayesian estimation using Markov Chain Monte Carlo (MCMC) approaches. These techniques are implemented using the optimisation software CasADi, and applied to two example problems: one where the oral absorption rate and bioavailability of the drug eflornithine are estimated using pharmacokinetic data from rats, and one where energy intake is estimated from body-mass measurements of mice exposed to monoclonal antibodies targeting the fibroblast growth factor receptor (FGFR) 1c. The results from the analysis are used to highlight the strengths and weaknesses of the methods used when applied to sparsely sampled data. The presented methods for optimal control are fast and robust, and can be recommended for use in drug discovery. The MCMC-based methods can have long running times and require more expertise from the user. The rigorous definition together with the illustrative examples and suggestions for software serve as a highly promising starting point for application of input-estimation methods to problems in drug discovery.

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1TPgzw4
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Sg9GTs
via IFTTT

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

Dancing Participation and Cardiovascular Disease Mortality

Publication date: Available online 1 March 2016
Source:American Journal of Preventive Medicine
Author(s): Dafna Merom, Ding Ding, Emmanuel Stamatakis
IntroductionLittle is known about whether cardiovascular benefits vary by activity type. Dance is a multidimensional physical activity of psychosocial nature. The study aimed to examine the association between dancing and cardiovascular disease mortality.MethodsA cohort study pooled 11 independent population surveys in the United Kingdom from 1995 to 2007, analyzed in 2014. Participants were 48,390 adults aged ≥40 years who were free of cardiovascular disease at baseline and consented to be linked to the National Death Registry. Respondents reported participation in light- or moderate-intensity dancing and walking in the past 4 weeks. Physical activity amount was calculated based on frequency, duration, and intensity of participation in various types of exercise. The main outcome was cardiovascular disease mortality based on ICD-9 codes 390−459 or ICD-10 codes I01−I99.ResultsDuring 444,045 person-years, 1,714 deaths caused by cardiovascular disease were documented. Moderate-intensity, but not light-intensity, dancing and walking were both inversely associated with cardiovascular disease mortality. In Cox regression models, the hazard ratios for cardiovascular disease mortality, adjusted for age, sex, SES, smoking, alcohol, BMI, chronic illness, psychosocial distress, and total physical activity amount, were 0.54 (95% CI=0.34, 0.87) for moderate-intensity dancing and 0.75 (95% CI=0.62, 0.90) for moderate-intensity walking.ConclusionsModerate-intensity dancing was associated with a reduced risk for cardiovascular disease mortality to a greater extent than walking. The association between dance and cardiovascular disease mortality may be explained by high-intensity bouts during dancing, lifelong adherence, or psychosocial benefits.

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1XYFc8H
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1ON9Wma
via IFTTT

It’s what’s inside that counts: egg contaminant concentrations are influenced by estimates of egg density, egg volume, and fresh egg mass

Abstract

In egg contaminant studies, it is necessary to calculate egg contaminant concentrations on a fresh wet weight basis and this requires accurate estimates of egg density and egg volume. We show that the inclusion or exclusion of the eggshell can influence egg contaminant concentrations, and we provide estimates of egg density (both with and without the eggshell) and egg-shape coefficients (used to estimate egg volume from egg morphometrics) for American avocet (Recurvirostra americana), black-necked stilt (Himantopus mexicanus), and Forster's tern (Sterna forsteri). Egg densities (g/cm3) estimated for whole eggs (1.056 ± 0.003) were higher than egg densities estimated for egg contents (1.024 ± 0.001), and were 1.059 ± 0.001 and 1.025 ± 0.001 for avocets, 1.056 ± 0.001 and 1.023 ± 0.001 for stilts, and 1.053 ± 0.002 and 1.025 ± 0.002 for terns. The egg-shape coefficients for egg volume (Kv ) and egg mass (Kw ) also differed depending on whether the eggshell was included (Kv = 0.491 ± 0.001; Kw = 0.518 ± 0.001) or excluded (Kv = 0.493 ± 0.001; Kw = 0.505 ± 0.001), and varied among species. Although egg contaminant concentrations are rarely meant to include the eggshell, we show that the typical inclusion of the eggshell in egg density and egg volume estimates results in egg contaminant concentrations being underestimated by 6–13 %. Our results demonstrate that the inclusion of the eggshell significantly influences estimates of egg density, egg volume, and fresh egg mass, which leads to egg contaminant concentrations that are biased low. We suggest that egg contaminant concentrations be calculated on a fresh wet weight basis using only internal egg-content densities, volumes, and masses appropriate for the species. For the three waterbirds in our study, these corrected coefficients are 1.024 ± 0.001 for egg density, 0.493 ± 0.001 for Kv , and 0.505 ± 0.001 for Kw .

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1TPLB5G
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1TlRfy6
via IFTTT

Effect of weekend admission on in-hospital mortality and functional outcomes for patients with acute subarachnoid haemorrhage (SAH)

Abstract

Background

Aneurysmal subarachnoid haemorrhage (aSAH) is an acute cerebrovascular event with high socioeconomic impact as it tends to affect younger patients. The recent NCEPOD study looking into management of aSAH has recommended that neurovascular units in the United Kingdom should aim to secure cerebral aneurysms within 48 h and that delays because of weekend admissions can increase the mortality and morbidity attributed to aSAH.

Method

We used data from a prospective audit of aSAH patients admitted between January 2009 and December 2011. The baseline demographic and clinical features of the weekend and weekday groups were compared using the chi-squared test and T-test. Cox proportional hazards models (Proc Phreg in SAS) were used to calculate the adjusted overall hazard of in-hospital death associated with admission on weekend, adjusting for age, sex, baseline WFNS grade, type of treatment received and time from scan to treatment. Sliding dichotomy analysis was used to estimate the difference in outcomes after SAH at 3 months in weekend and weekday admissions.

Results

Those admitted on weekends had a significantly higher scan to treatment time (83.05 ± 83.4 h vs 40.4 ± 53.4 h, P < 0.0001) and admission to treatment (71.59 ± 79.8 h vs 27.5 ± 44.3 h, P < 0.0001) time. After adjustments for adjusted for relevant covariates weekend admission was statistically significantly associated with excess in-hospital mortality (HR = 2.1, CL [1.13–4.0], P = 0.01). After adjustments for all the baseline covariates, the sliding dichotomy analysis did not show effects of weekend admission on long-term outcomes on the good, intermediate and worst prognostic bands.

Conclusions

This study provides important data showing excess in-hospital mortality of patients with SAH on weekend admissions served by the United Kingdom's National Health Service.; However, there were no effects of weekend admission on long-term outcomes.

from NeuroSurgery via xlomafota13 on Inoreader http://ift.tt/1oWtRdI
via IFTTT

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

The effect of dopaminergic therapy on intraoperative microelectrode recordings for subthalamic deep brain stimulation under GA: Letter to the editor

from NeuroSurgery via xlomafota13 on Inoreader http://ift.tt/1LT3ryk
via IFTTT

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

Comments on “Intraforaminal ozone therapy and particular side effects: preliminary results and early warning”

from NeuroSurgery via xlomafota13 on Inoreader http://ift.tt/1oWsk7D
via IFTTT

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

Implications of limiting mechanical thrombectomy to patients with emergent large vessel occlusion meeting top tier evidence criteria

Background

Recent guidelines for endovascular management of emergent large vessel occlusion (ELVO) award top tier evidence to the same selective criteria in recent trials. We aimed to understand how guideline adherence would have impacted treatment numbers and outcomes in a cohort of patients from a comprehensive stroke center.

Methods

A retrospective observational study was conducted using consecutive emergent endovascular patients. Mechanical thrombectomy (MT) was performed with stent retrievers or large bore clot aspiration catheters. Procedural outcomes were compared between patients meeting, and those failing to meet, top tier evidence criteria.

Results

126 patients receiving MT from January 2012 to June 2015 were included (age 31–89 years, National Institutes of Health Stroke Scale (NIHSS) score 2–38); 62 (49%) patients would have been excluded if top tier criteria were upheld: pretreatment NIHSS score <6 (10%), Alberta Stroke Program Early CT score <6 (6.5%), premorbid modified Rankin Scale (mRS) score ≥2 (27%), M2 occlusion (10%), posterior circulation (32%), symptom to groin puncture >360 min (58%). 26 (42%) subjects had more than one top tier exclusion. Symptomatic intracerebral hemorrhage (sICH) and systemic hemorrhage rates were similar between the groups. 3 month mortality was 45% in those lacking top tier evidence compared with 26% (p=0.044), and 3 month mRS score 0–2 was 33% versus 46%, respectively (NS). After adjusting for potential confounders, top tier treatment was not associated with neurological improvement during hospitalization (β –8.2; 95% CI –24.6 to –8.2; p=0.321), 3 month mortality (OR=0.38; 95% CI 0.08 to 1.41), or 3 month favorable mRS (OR=0.97; 95% CI 0.28 to 3.35).

Conclusions

Our study showed that with strict adherence to top tier evidence criteria, half of patients may not be considered for MT. Our data indicate no increased risk of sICH and a potentially higher mortality that is largely due to treatment of patients with basilar occlusions and those treated at an extended time window. Despite this, good functional recovery is possible, and consideration of MT in patients not meeting top tier evidence criteria may be warranted.

from NeuroSurgery via xlomafota13 on Inoreader http://ift.tt/1L2Ob76
via IFTTT

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

Outcome and recurrence one year after paediatric arterial ischaemic stroke in a population-based cohort

Abstract

Objective:

Arterial ischaemic stroke (AIS) is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood AIS have been completed. We aimed to investigate the outcome of childhood AIS 12 months after the event in a population-based cohort.

Methods:

Children aged 29 days to less than 16 years with radiologically confirmed AIS occurring over a 1-year period residing in southern England (population 5.99 million children) were eligible for inclusion. Outcome was assessed during a home-visit using the Paediatric Stroke Outcome Measure (PSOM). Parental impressions of recovery were assessed using the Paediatric Stroke Recurrence and Recovery Questionnaire (RRQ). PSOM score was estimated via telephone interview or clinician interview whenever home-visit was not possible.

Results:

96 children with AIS were identified. 2 children were lost to follow-up. 9/94 (10%) of children died before the 12-month follow-up. One child had an AIS recurrence. PSOM scores were available for 78 of 85 living children at follow-up. 39/78 (50%) had a good outcome (total PSOM score <1) and 39/78 (50%) had a poor outcome. Seizures at onset of AIS were associated with a poor outcome (Odds Ratio 3.5 95% CI 1.16-10.6). 28/73 (38%) children were judged by their carers to have fully recovered. 10/84 (12%) of children had recurrent seizures and 17/84 (20%) reported recurrent headaches.

Interpretation:

AIS carries a significant risk of mortality and long-term neurological deficit. However, the rates of mortality, recurrence and neurological impairment were markedly lower in this study than previously published figures in the UK. This article is protected by copyright. All rights reserved.

from Neurology via xlomafota13 on Inoreader http://ift.tt/1QRL7x0
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1oWuzI8
via IFTTT

A novel approach to the management of carotid blowout syndrome: the use of thrombin in a case of failed covered stenting

Acute hemorrhage relating to an expanding pseudoaneurysm of the carotid artery is referred to as carotid blowout syndrome (CBS). CBS is associated with a high morbidity and mortality. We describe the case of a patient who presented with dysphagia and a pulsatile mass in the neck. Imaging revealed a pseudoaneurysm originating from the bifurcation of the distal right common carotid artery. On neuroangiography the patient lacked sufficient collaterals to allow for vessel sacrifice. A decision was made to use covered stents to prevent flow into the pseudoaneurysm while maintaining vessel patency. Despite placement of multiple covered stents there was residual slow filling of the pseudoaneurysm. We augmented this therapy with direct percutaneous thrombin injection into the pseudoaneurysm. This resulted in complete thrombosis of the pseudoaneurysm. For recalcitrant lesions in which the usual methods of stopping blood flow to the pseudoaneurysmal sac fail, an adjuvant approach with thrombin should be considered.

from NeuroSurgery via xlomafota13 on Inoreader http://ift.tt/1ngS78K
via IFTTT

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

Longitudinal study on diffusion tensor imaging and diffusion tensor tractography following spinal cord contusion injury in rats

Abstract

Introduction

Diffusion tensor imaging (DTI) as a potential technology has been used in spinal cord injury (SCI) studies, but the longitudinal evaluation of DTI parameters after SCI, and the correlation between DTI parameters and locomotor outcomes need to be defined.

Methods

Adult Wistar rats (n = 6) underwent traumatic thoracic cord contusion by an NYU impactor. DTI and Basso–Beattie–Bresnahan datasets were collected pre-SCI and 1, 3, 7, 14, and 84 days post-SCI. Diffusion tensor tractography (DTT) of the spinal cord was also generated. Fractional anisotropy (FA) and connection rate of fibers at the injury epicenter and at 5 mm rostral/caudal to the epicenter were calculated. The variations of these parameters after SCI were observed by one-way analysis of variance and the correlations between these parameters and motor function were explored by Pearson's correlation.

Results

FA at the epicenter decreased most remarkably on day 1 post-SCI (from 0.780 ± 0.012 to 0.330 ± 0.015), and continued to decrease slightly by day 3 post-SCI (0.313 ± 0.015), while other parameters decreased significantly over the first 3 days after SCI. DTT showed residual fibers concentrated on ventral and ventrolateral sides of the cord. Moreover, FA at the epicenter exhibited the strongest correlation (r = 0.887, p = 0.000) with the locomotion performance.

Conclusion

FA was sensitive to degeneration in white matter and DTT could directly reflect the distribution of the residual white matter. Moreover, days 1 to 3 post-SCI may be the optimal time window for SCI examination and therapy.

from Neurology via xlomafota13 on Inoreader http://ift.tt/1VOM2fD
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1oWuzI6
via IFTTT

New title will be launched on J-STAGE.Journal of Medical and Dental Sciences

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

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

The new issue is now available.The Tohoku Journal of Experimental Medicine

March

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1QcTTo3
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfP7Xl
via IFTTT

The new issue is now available.Food Hygiene and Safety Science (Shokuhin Eiseigaku Zasshi)

Vol.57 No.1

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1P6gXUP
via IFTTT

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

The new issue is now available.Bird Research

Vol.12

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1SfOhK4
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfP5ia
via IFTTT

The new issue is now available.Journal of the Sedimentological Society of Japan

Vol.74 No.2

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

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

The new issue is now available.Proceedings of the Japan Joint Automatic Control Conference

Vol.57

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfP5i7
via IFTTT

The new issue is now available.Nihon Fukubu Kyukyu Igakkai Zasshi (Journal of Abdominal Emergency Medicine)

Vol.35 No.7

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

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

The new issue is now available.The Japanese Journal of Rural Economics

Vol.7

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfP7Xb
via IFTTT

The new issue is now available.Ningen to kankyo

Vol.42 No.1

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1RE9pY4
via IFTTT

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

Obstructive Sleep Apnea, Sleep Duration, and Fasting Glucose

American Journal of Respiratory and Critical Care Medicine, Volume 193, Issue 5, Page 579-580, March 1, 2016.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/1T6oeWL
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/1T6oqVS
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfP7X9
via IFTTT

The new issue is now available.Zairyo-to-Kankyo

Vol.64 No.8

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

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

The new issue is now available.Journal of Food System Research

Vol.22 No.3

from #ORL-AlexandrosSfakianakis via simeraentaxei on Inoreader http://ift.tt/1XPqwN4
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1SfP5i3
via IFTTT

Just Say No! Smoking Abstinence Works

American Journal of Respiratory and Critical Care Medicine, Volume 193, Issue 5, Page 476-477, March 1, 2016.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/1T6oi91
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/1LSXXU1
via IFTTT

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

Association of TERT promoter mutations with telomerase expression in melanoma

Abstract

Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were first discovered in melanoma (Horn et al., 2013; Huang et al., 2013) and subsequently in several other cancer types (Killela et al., 2013). These mutations occur mainly at positions −124 bp (chr5, 1,295,228 C>T hg19 coordinate) and −146 bp (chr5, 1,295,250 C>T hg19 coordinate) from the ATG translation start site (Heidenreich et al., 2014; Horn et al., 2013; Huang et al., 2013), and are hereafter termed as −124C>T and –146C>T, respectively (Figure 1a). Mutually exclusive −124C>T and –146C>T mutations have been detected in more than 65% of melanomas (Network, 2015). These mutations contribute to TERT transcriptional upregulation by recruiting the GABPA/B1 transcription factor (Bell et al., 2015).

This article is protected by copyright. All rights reserved.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1SflIMM
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1QkG0C0
via IFTTT

Association of TERT promoter mutations with telomerase expression in melanoma

Abstract

Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were first discovered in melanoma (Horn et al., 2013; Huang et al., 2013) and subsequently in several other cancer types (Killela et al., 2013). These mutations occur mainly at positions −124 bp (chr5, 1,295,228 C>T hg19 coordinate) and −146 bp (chr5, 1,295,250 C>T hg19 coordinate) from the ATG translation start site (Heidenreich et al., 2014; Horn et al., 2013; Huang et al., 2013), and are hereafter termed as −124C>T and –146C>T, respectively (Figure 1a). Mutually exclusive −124C>T and –146C>T mutations have been detected in more than 65% of melanomas (Network, 2015). These mutations contribute to TERT transcriptional upregulation by recruiting the GABPA/B1 transcription factor (Bell et al., 2015).

This article is protected by copyright. All rights reserved.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1SflIMM
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Lumfc5
via IFTTT

Association of TERT promoter mutations with telomerase expression in melanoma

Abstract

Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were first discovered in melanoma (Horn et al., 2013; Huang et al., 2013) and subsequently in several other cancer types (Killela et al., 2013). These mutations occur mainly at positions −124 bp (chr5, 1,295,228 C>T hg19 coordinate) and −146 bp (chr5, 1,295,250 C>T hg19 coordinate) from the ATG translation start site (Heidenreich et al., 2014; Horn et al., 2013; Huang et al., 2013), and are hereafter termed as −124C>T and –146C>T, respectively (Figure 1a). Mutually exclusive −124C>T and –146C>T mutations have been detected in more than 65% of melanomas (Network, 2015). These mutations contribute to TERT transcriptional upregulation by recruiting the GABPA/B1 transcription factor (Bell et al., 2015).

This article is protected by copyright. All rights reserved.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1SflIMM
via IFTTT

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

Interaction of extracellular S100A4 with RAGE prompts prometastatic activation of A375 melanoma cells

Abstract

S100A4, a member of the S100 protein family of EF-hand calcium-binding proteins, is overexpressed in various tumour entities, including melanoma, and plays an important role in tumour progression. Several studies in epithelial and mesenchymal tumours revealed a correlation between extracellular S100A4 and metastasis. However, exact mechanisms how S100A4 stimulates metastasis in melanoma are still unknown. From a pilot experiment on baseline synthesis and secretion of S100A4 in human melanoma cell lines, which are in broad laboratory use, A375 wild-type cells and, additionally, newly generated A375 cell lines stably transfected with human S100A4 (A375-hS100A4) or human receptor for advanced glycation endproducts (A375-hRAGE), were selected to investigate the influence of extracellular S100A4 on cell motility, adhesion, migration and invasion in more detail. We demonstrated that A375 cells actively secrete S100A4 in the extracellular space via an endoplasmic reticulum-Golgi-dependent pathway. S100A4 overexpression and secretion resulted in prometastatic activation of A375 cells. Moreover, we determined the influence of S100A4-RAGE interaction and its blockade on A375, A375-hS100A4, A375-hRAGE cells, and showed that interaction of RAGE with extracellular S100A4 contributes to the observed activation of A375 cells. This investigation reveals additional molecular targets for therapeutic approaches aiming at blockade of ligand binding to RAGE or RAGE signalling to inhibit melanoma metastasis.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1L2hpmC
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Lume84
via IFTTT

Interaction of extracellular S100A4 with RAGE prompts prometastatic activation of A375 melanoma cells

Abstract

S100A4, a member of the S100 protein family of EF-hand calcium-binding proteins, is overexpressed in various tumour entities, including melanoma, and plays an important role in tumour progression. Several studies in epithelial and mesenchymal tumours revealed a correlation between extracellular S100A4 and metastasis. However, exact mechanisms how S100A4 stimulates metastasis in melanoma are still unknown. From a pilot experiment on baseline synthesis and secretion of S100A4 in human melanoma cell lines, which are in broad laboratory use, A375 wild-type cells and, additionally, newly generated A375 cell lines stably transfected with human S100A4 (A375-hS100A4) or human receptor for advanced glycation endproducts (A375-hRAGE), were selected to investigate the influence of extracellular S100A4 on cell motility, adhesion, migration and invasion in more detail. We demonstrated that A375 cells actively secrete S100A4 in the extracellular space via an endoplasmic reticulum-Golgi-dependent pathway. S100A4 overexpression and secretion resulted in prometastatic activation of A375 cells. Moreover, we determined the influence of S100A4-RAGE interaction and its blockade on A375, A375-hS100A4, A375-hRAGE cells, and showed that interaction of RAGE with extracellular S100A4 contributes to the observed activation of A375 cells. This investigation reveals additional molecular targets for therapeutic approaches aiming at blockade of ligand binding to RAGE or RAGE signalling to inhibit melanoma metastasis.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1L2hpmC
via IFTTT

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

Interaction of extracellular S100A4 with RAGE prompts prometastatic activation of A375 melanoma cells

Abstract

S100A4, a member of the S100 protein family of EF-hand calcium-binding proteins, is overexpressed in various tumour entities, including melanoma, and plays an important role in tumour progression. Several studies in epithelial and mesenchymal tumours revealed a correlation between extracellular S100A4 and metastasis. However, exact mechanisms how S100A4 stimulates metastasis in melanoma are still unknown. From a pilot experiment on baseline synthesis and secretion of S100A4 in human melanoma cell lines, which are in broad laboratory use, A375 wild-type cells and, additionally, newly generated A375 cell lines stably transfected with human S100A4 (A375-hS100A4) or human receptor for advanced glycation endproducts (A375-hRAGE), were selected to investigate the influence of extracellular S100A4 on cell motility, adhesion, migration and invasion in more detail. We demonstrated that A375 cells actively secrete S100A4 in the extracellular space via an endoplasmic reticulum-Golgi-dependent pathway. S100A4 overexpression and secretion resulted in prometastatic activation of A375 cells. Moreover, we determined the influence of S100A4-RAGE interaction and its blockade on A375, A375-hS100A4, A375-hRAGE cells, and showed that interaction of RAGE with extracellular S100A4 contributes to the observed activation of A375 cells. This investigation reveals additional molecular targets for therapeutic approaches aiming at blockade of ligand binding to RAGE or RAGE signalling to inhibit melanoma metastasis.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1L2hpmC
via IFTTT

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

PRAME as a Biomarker in Uveal Melanoma

Purpose: Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor BAP1. Nevertheless, a small percentage of Class 1 tumors give rise to metastatic disease. The purpose of this study was to identify biomarkers of metastasis in Class 1 tumors.

Experimental Design: A total of 389 consecutive patients with UM were assigned to Class 1 or Class 2 using a prospectively validated 12-gene prognostic classifier. Selected tumors were further analyzed using global GEP and single nucleotide polymorphism microarrays. PRAME (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by qPCR.

Results: Among Class 1 UMs, the most significant predictor of metastasis was PRAME mRNA expression (P = 0.0006). The 5-year actuarial rate of metastasis was 0% for Class1^PRAME–, 38% for Class1^PRAME+, and 71% for Class 2 tumors. Median metastasis-free survival for Class1^PRAME+ patients was 88 months, compared to 32 months for Class 2 patients. Findings were validated using three independent datasets, including one using disomy 3 to identify low-risk UM. Chromosome copy number changes associated with Class1^PRAME+ tumors included gain of 1q, 6p, 8q, and 9q and loss of 6q and 11q. PRAME expression was associated with larger tumor diameter (P = 0.05) and SF3B1 mutations (P = 0.003).

Conclusions: PRAME is an independent prognostic biomarker in UM, which identifies increased metastatic risk in patients with Class 1 or disomy 3 tumors. This finding may further enhance the accuracy of prognostic testing and precision medicine for UM. Clin Cancer Res; 22(5); 1234–42. ©2016 AACR.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1XXU2wd
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1QkFZ0Z
via IFTTT

PRAME as a Biomarker in Uveal Melanoma

Purpose: Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor BAP1. Nevertheless, a small percentage of Class 1 tumors give rise to metastatic disease. The purpose of this study was to identify biomarkers of metastasis in Class 1 tumors.

Experimental Design: A total of 389 consecutive patients with UM were assigned to Class 1 or Class 2 using a prospectively validated 12-gene prognostic classifier. Selected tumors were further analyzed using global GEP and single nucleotide polymorphism microarrays. PRAME (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by qPCR.

Results: Among Class 1 UMs, the most significant predictor of metastasis was PRAME mRNA expression (P = 0.0006). The 5-year actuarial rate of metastasis was 0% for Class1^PRAME–, 38% for Class1^PRAME+, and 71% for Class 2 tumors. Median metastasis-free survival for Class1^PRAME+ patients was 88 months, compared to 32 months for Class 2 patients. Findings were validated using three independent datasets, including one using disomy 3 to identify low-risk UM. Chromosome copy number changes associated with Class1^PRAME+ tumors included gain of 1q, 6p, 8q, and 9q and loss of 6q and 11q. PRAME expression was associated with larger tumor diameter (P = 0.05) and SF3B1 mutations (P = 0.003).

Conclusions: PRAME is an independent prognostic biomarker in UM, which identifies increased metastatic risk in patients with Class 1 or disomy 3 tumors. This finding may further enhance the accuracy of prognostic testing and precision medicine for UM. Clin Cancer Res; 22(5); 1234–42. ©2016 AACR.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1XXU2wd
via IFTTT

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

PRAME as a Biomarker in Uveal Melanoma

Purpose: Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor BAP1. Nevertheless, a small percentage of Class 1 tumors give rise to metastatic disease. The purpose of this study was to identify biomarkers of metastasis in Class 1 tumors.

Experimental Design: A total of 389 consecutive patients with UM were assigned to Class 1 or Class 2 using a prospectively validated 12-gene prognostic classifier. Selected tumors were further analyzed using global GEP and single nucleotide polymorphism microarrays. PRAME (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by qPCR.

Results: Among Class 1 UMs, the most significant predictor of metastasis was PRAME mRNA expression (P = 0.0006). The 5-year actuarial rate of metastasis was 0% for Class1^PRAME–, 38% for Class1^PRAME+, and 71% for Class 2 tumors. Median metastasis-free survival for Class1^PRAME+ patients was 88 months, compared to 32 months for Class 2 patients. Findings were validated using three independent datasets, including one using disomy 3 to identify low-risk UM. Chromosome copy number changes associated with Class1^PRAME+ tumors included gain of 1q, 6p, 8q, and 9q and loss of 6q and 11q. PRAME expression was associated with larger tumor diameter (P = 0.05) and SF3B1 mutations (P = 0.003).

Conclusions: PRAME is an independent prognostic biomarker in UM, which identifies increased metastatic risk in patients with Class 1 or disomy 3 tumors. This finding may further enhance the accuracy of prognostic testing and precision medicine for UM. Clin Cancer Res; 22(5); 1234–42. ©2016 AACR.

from melanoma2 via als.fakia on Inoreader http://ift.tt/1XXU2wd
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1QkG0lo
via IFTTT

Id1 Regulates E2F1 Degradation and Cancer Chemoresistance

Purpose: Chemoresistance is a major obstacle in cancer therapy. We found that fluorouracil (5-FU)-resistant esophageal squamous cell carcinoma cell lines, established through exposure to increasing concentrations of 5-FU, showed upregulation of Id1, IGF2, and E2F1. We hypothesized that these genes may play an important role in cancer chemoresistance.

Experimental Design: In vitro and in vivo functional assays were performed to study the effects of Id1–E2F1–IGF2 signaling in chemoresistance. Quantitative real-time PCR, Western blotting, immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were used to investigate the molecular mechanisms by which Id1 regulates E2F1 and by which E2F1 regulates IGF2. Clinical specimens, tumor tissue microarray, and Gene Expression Omnibus datasets were used to analyze the correlations between gene expressions and the relationships between expression profiles and patient survival outcomes.

Results: Id1 conferred 5-FU chemoresistance through E2F1-dependent induction of thymidylate synthase expression in esophageal cancer cells and tumor xenografts. Mechanistically, Id1 protects E2F1 protein from degradation and increases its expression by binding competitively to Cdc20, whereas E2F1 mediates Id1-induced upregulation of IGF2 by binding directly to the IGF2 promoter and activating its transcription. The expression level of E2F1 was positively correlated with that of Id1 and IGF2 in human cancers. More importantly, concurrent high expression of Id1 and IGF2 was associated with unfavorable patient survival in multiple cancer types.

Conclusions: Our findings define an intricate E2F1-dependent mechanism by which Id1 increases thymidylate synthase and IGF2 expressions to promote cancer chemoresistance. The Id1–E2F1–IGF2 regulatory axis has important implications for cancer prognosis and treatment. Clin Cancer Res; 22(5); 1243–55. ©2015 AACR.

from squamous cell carcinoma via ok on Inoreader http://ift.tt/1LtJPWz
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1XY5wjt
via IFTTT

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

LNA-i-miR-221 Inhibitor Overcomes Melphalan Resistance

Purpose: The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma.

Experimental Design: Here we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan.

Results: miR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of human bone marrow (BM) stromal cells. Decreased multiple myeloma cell growth induced by inhibition of miR-221/222 plus melphalan was associated with a marked upregulation of pro-apoptotic BBC3/PUMA protein, a miR-221/222 target, as well as with modulation of drug influx–efflux transporters SLC7A5/LAT1 and the ABC transporter ABCC1/MRP1. Finally, in vivo treatment of SCID/NOD mice bearing human melphalan-refractory multiple myeloma xenografts with systemic locked nucleic acid (LNA) inhibitors of miR-221 (LNA-i-miR-221) plus melphalan overcame drug resistance, evidenced by growth inhibition with significant antitumor effects together with modulation of PUMA and ABCC1 in tumors retrieved from treated mice.

Conclusions: Taken together, our findings provide the proof of concept that LNA-i-miR-221 can reverse melphalan resistance in preclinical models of multiple myeloma, providing the framework for clinical trials to overcome drug resistance, and improve patient outcome in multiple myeloma. Clin Cancer Res; 22(5); 1222–33. ©2015 AACR.

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RDS01Y
via IFTTT

Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma

Recent studies in lung adenocarcinoma established a clinically relevant histomorphology-based classification. In contrast, no morphological classifiers have yet been implemented into routine diagnostics for lung squamous cell carcinoma (SQCC). However, morphology-based characteristics putatively impacting on survival have been proposed. We analysed a cohort of 541 SQCC patients with complete clinical follow-up data for morphological characteristics (keratinisation, tumour cell budding, size of tumour cell nests, nuclear size and stromal content). Morphological characteristics were correlated with clinical data and patient outcome. Keratinisation, budding, stromal content and tumour cell nest size, but not nuclear size, were associated with distinct clinicopathological characteristics and s…

MedWorm Sponsor Message: Directory of the best January Sales in the UK. Find the best Christmas presents too.

from squamous cell carcinoma via ok on Inoreader http://ift.tt/1TkW1Mp
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Lu1ZaM
via IFTTT

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

Metformin and Pancreatic Cancer Survival

Metformin offers no survival advantage in patients with metastatic pancreatic cancer. Despite promising experimental evidence suggesting an antitumor effect of metformin, its impact on the survival of advanced pancreatic cancer is likely very limited. Future studies may need to consider its role in early-stage pancreatic cancer. Clin Cancer Res; 22(5); 1031–3. ©2015 AACR.

See related article by Reni et al., p. 1076

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1QIRqg1
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RDS01T
via IFTTT

Synergistic Antitumor Effect of RFA and PD-1 Blockade

Purpose: Radiofrequency ablation (RFA) has been shown to elicit tumor-specific T-cell immune responses, but is not sufficient to prevent cancer progression. Here, we investigated immune-suppressive mechanisms limiting the efficacy of RFA.

Experimental Design: We performed a retrospective case-controlled study on patients with synchronous colorectal cancer liver metastases who had received primary tumor resection with or without preoperative RFA for liver metastases. Tumor-infiltrating T cells and tumoral PD-L1 expression in human colorectal cancer tissues were analyzed by immunohistochemistry. T-cell immune responses and PD-1/PD-L1 expression were also characterized in an RFA mouse model. In addition, the combined effect of RAF and PD-1 blockade was evaluated in the mouse RFA model.

Results: We found that RFA treatment of liver metastases increased not only T-cell infiltration, but also PD-L1 expression in primary human colorectal tumors. Using mouse tumor models, we demonstrated that RFA treatment of one tumor initially enhanced a strong T-cell–mediated immune response in tumor. Nevertheless, tumor quickly overcame the immune responses by inhibiting the function of CD8+ and CD4+ T cells, driving a shift to higher regulatory T-cell to Teff ratio, and upregulating PD-L1/PD-1 expression. Furthermore, we established that the combined therapy of RFA and anti–PD-1 antibodies significantly enhanced T-cell immune responses, resulting in stronger antitumor immunity and prolonged survival.

Conclusions: The PD-L1–PD-1 axis plays a critical role in dampening RFA-induced antitumor immune responses, and this study provides a strong rationale for combining RFA and the PD-L1/PD-1 blockade in the clinical setting. Clin Cancer Res; 22(5); 1173–84. ©2016 AACR.

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RDS29Z
via IFTTT

Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma

Recent studies in lung adenocarcinoma established a clinically relevant histomorphology-based classification. In contrast, no morphological classifiers have yet been implemented into routine diagnostics for lung squamous cell carcinoma (SQCC). However, morphology-based characteristics putatively impacting on survival have been proposed. We analysed a cohort of 541 SQCC patients with complete clinical follow-up data for morphological characteristics (keratinisation, tumour cell budding, size of tumour cell nests, nuclear size and stromal content). Morphological characteristics were correlated with clinical data and patient outcome. Keratinisation, budding, stromal content and tumour cell nest size, but not nuclear size, were associated with distinct clinicopathological characteristics and s…

from squamous cell carcinoma via ok on Inoreader http://ift.tt/1ngzwcM
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1XY5yI0
via IFTTT

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

Comment surveiller une gastrite ? Une métaplasie intestinale ? Quelles sont les recommandations actuelles ? Peut-on faire mieux avec la chromoscopie électronique ?

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1RiC2Yn
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Lu1ZaC
via IFTTT

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

ESR1 Mutations in Breast Cancer

Wang and colleagues demonstrate that digital droplet PCR (ddPCR) identified ESR1 mutations in 7% of primary breast cancers. ESR1 mutations were also readily detected in metastatic tissues and circulating tumor DNA in the blood. These results suggest that ddPCR may be amendable for monitoring tumor burden, and to predict relapse. Clin Cancer Res; 22(5); 1034–6. ©2015 AACR.

See related article by Wang et al., p. 1130

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

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

Blind restoration and resolution enhancement of images based on complex filtering

Abstract

Recently, a blind resolution enhancement method that uses a two-dimensional and single-input multiple-output extension of the constant modulus algorithm has been developed for pure translational motion. The method works well in case of low bit depth unobserved true images, but its performance decreases for high bit depth true images. In this work, we propose a refined scheme in which complex representation of images and a set of complex deconvolution FIR filters are used. Simulations show that the refined method succeeds in reconstructing the low and high bit depth true images without the knowledge of blur parameters. Visual results for the restoration case (single image, no subsampling) are also given. No assumption is made about the blurs except that they have low-pass characteristics. Also, they do not have to be the same for the observed low-resolution images and they do not need to be shift invariant.

from Biomedical Engineering via ola Kala on Inoreader http://ift.tt/1oLLigm
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1XY5w2X
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Qpv6c1
via IFTTT

CXCL12 and Prognosis in Stage I Nonseminomas

Purpose: Up to 50% of patients diagnosed with stage I nonseminomatous germ cell tumors (NSGCTs) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up front. Late toxicities from chemotherapy are increasingly recognized. Based on a potential biologic role in germ cells/tumors and pilot data, our aim was to evaluate tumor expression of the chemokine CXCL12 alongside previously proposed markers as clinically useful biomarkers of relapse.

Experimental Design: Immunohistochemistry for tumor expression of CXCL12 was assessed as a biomarker of relapse alongside vascular invasion, histology (percentage embryonal carcinoma), and MIB1 staining for proliferation in formalin-fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCTs.

Results: TE08/TE22 trial patients had a 76.4% 2-year relapse-free rate, and both CXCL12 expression and percentage embryonal carcinoma provided prognostic value independently of vascular invasion (stratified log rank test P = 0.006 for both). There was no additional prognostic value for MIB1 staining. A model using CXCL12, percentage embryonal carcinoma, and VI defines three prognostic groups that were independently validated.

Conclusions: CXCL12 and percentage embryonal carcinoma both stratify patients' relapse risk over and above vascular invasion alone. This is anticipated to improve the stratification of patients and identify high-risk cases to be considered for adjuvant therapy. Clin Cancer Res; 22(5); 1265–73. ©2015 AACR.

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

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1L2T0NH
via IFTTT

Proposal of a prognostically relevant grading scheme for pulmonary squamous cell carcinoma

Recent studies in lung adenocarcinoma established a clinically relevant histomorphology-based classification. In contrast, no morphological classifiers have yet been implemented into routine diagnostics for lung squamous cell carcinoma (SQCC). However, morphology-based characteristics putatively impacting on survival have been proposed. We analysed a cohort of 541 SQCC patients with complete clinical follow-up data for morphological characteristics (keratinisation, tumour cell budding, size of tumour cell nests, nuclear size and stromal content). Morphological characteristics were correlated with clinical data and patient outcome. Keratinisation, budding, stromal content and tumour cell nest size, but not nuclear size, were associated with distinct clinicopathological characteristics and s...

from squamous cell carcinoma via ok on Inoreader http://ift.tt/1oMDCKT
via IFTTT

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