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https://www.readbyqxmd.com/read/27911273/robust-detection-of-immune-transcripts-in-ffpe-samples-using-targeted-rna-sequencing
#1
Benjamin E Paluch, Sean T Glenn, Jeffrey M Conroy, Antonios Papanicolau-Sengos, Wiam Bshara, Angela R Omilian, Elizabeth Brese, Mary Nesline, Blake Burgher, Jonathan Andreas, Kunle Odunsi, Kevin Eng, Ji He, Maochun Qin, Mark Gardner, Lorenzo Galluzzi, Carl D Morrison
Current criteria for identifying cancer patients suitable for immunotherapy with immune checkpoint blockers (ICBs) are subjective and prone to misinterpretation, as they mainly rely on the visual assessment of CD274 (best known as PD-L1) expression levels by immunohistochemistry (IHC). To address this issue, we developed a RNA sequencing (RNAseq)-based approach that specifically measures the abundance of immune transcripts in formalin-fixed paraffin embedded (FFPE) specimens. Besides exhibiting superior sensitivity as compared to whole transcriptome RNAseq, our assay requires little starting material, implying that it is compatible with RNA degradation normally caused by formalin...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910855/l-type-calcium-channels-regulate-filopodia-stability-and-cancer-cell-invasion-downstream-of-integrin-signalling
#2
Guillaume Jacquemet, Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu, Johanna Ivaska
Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27910284/resting-heart-rate-is-an-independent-predictor-of-death-in-patients-with-colorectal-pancreatic-and-non-small-cell-lung-cancer-results-of-a-prospective-cardiovascular-long-term-study
#3
Markus S Anker, Nicole Ebner, Bert Hildebrandt, Jochen Springer, Marianne Sinn, Hanno Riess, Stefan D Anker, Ulf Landmesser, Wilhelm Haverkamp, Stephan von Haehling
AIMS: Patients with advanced cancer have been shown to suffer from abnormal cardiac function and impaired exercise capacity that may contribute to their impaired quality of life. As tachycardia is considered as a sign of potential early cardiac damage, we sought to determine whether resting heart rate and other ECG-derived variables have prognostic value. METHODS AND RESULTS: From 2005 to 2010, we enrolled 145 patients with histologically confirmed cancer (36 colorectal, 72 pancreatic, and 37 non-small cell lung cancer patients) and 59 healthy controls...
December 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27909967/selective-blockade-of-%C3%AE-2-adrenoceptor-subtypes-modulates-contractility-of-rat-myocardium
#4
T L Zefirov, L I Khisamieva, N I Ziyatdinova, A L Zefirov
The study examined the dose-dependent effects of selective antagonists of α2A/D-, α2B-, and α2C- adrenoceptors applied in concentrations of 10(-9)-10(-5) M on atrial and ventricular contractility of rat myocardium in vitro. Selective blockade of each α2-adrenoceptor subtype affected the contractile force of the atrial and ventricular strips. Various concentrations of α2A/D- and α2C-adrenoceptor antagonists produced positive inotropic effect on ventricular strips and negative effect on atrial strips. α2B-Adrenoceptor blocker in the majority of the tested concentrations produced a positive inotropic effect in both atria and ventricles...
December 2, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27909849/monitoring-contaminants-of-emerging-concern-from-tertiary-wastewater-treatment-plants-using-passive-sampling-modelled-with-performance-reference-compounds
#5
Tamanna Sultana, Craig Murray, M Ehsanul Hoque, Chris D Metcalfe
The Lake Simcoe watershed in Ontario, Canada is an important recreational area and a recharge zone for groundwater resources. Lake Simcoe is a relatively shallow lotic system that has been impacted by urban development, recreation, industry and agriculture. As part of a watershed management plan, six wastewater treatment plants (WWTPs) located in this catchment basin were selected to measure the inputs of contaminants of emerging concern (CECs) of wastewater origin. These WWTPs were recently upgraded to tertiary treatment for phosphorus removal...
December 2016: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/27909438/donor-specific-regulatory-t-cells-acquired-from-tolerant-mice-bearing-cardiac-allograft-promote-mixed-chimerism-and-prolong-intestinal-allograft-survival
#6
Xiao-Fei Shen, Jin-Peng Jiang, Jian-Jun Yang, Wei-Zhong Wang, Wen-Xian Guan, Jun-Feng Du
The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation (SBT), which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts, such as skin, kidney, and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27908944/use-of-neuromuscular-blockers-during-therapeutic-hypothermia-after-cardiac-arrest-a-nursing-protocol
#7
Coraline Boulila, Samia Ben Abdallah, Aude Marincamp, Vincent Coic, Romuald Lauverjat, Nicole Ericher, Wulfran Bougouin, Jean-Paul Mira, Alain Cariou, Guillaume Geri
BACKGROUND: Neuromuscular blockers used to prevent shivering during therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest are associated with adverse events. OBJECTIVE: To assess the influence of a nurse-implemented protocol on use of neuromuscular blockers in patients treated with 24-hour therapeutic hypothermia after out-of-hospital cardiac arrest. METHODS: A before and after study was done in a 24-bed cardiac arrest center...
December 2016: Critical Care Nurse
https://www.readbyqxmd.com/read/27908918/alpha-blockers-for-treatment-of-ureteric-stones-systematic-review-and-meta-analysis
#8
John M Hollingsworth, Benjamin K Canales, Mary A M Rogers, Shyam Sukumar, Phyllis Yan, Gretchen M Kuntz, Philipp Dahm
OBJECTIVE:  To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones. DESIGN:  Systematic review and meta-analysis. DATA SOURCES:  Cochrane Central Register of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016. REVIEW METHODS:  Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible...
December 1, 2016: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/27908836/gq-and-gs-signaling-acting-in-synergy-to-control-glp-1-secretion
#9
Maria Hauge, Jeppe Pio Ekberg, Maja Storm Engelstoft, Pascal Timshel, Andreas N Madsen, Thue W Schwartz
GPR40 is generally known to signal through Gq. However, in transfected cells, certain synthetic agonists can make the receptor signal also through Gs and cAMP (Hauge et al., 2015). Here we find that, in colonic crypt cultures, the GLP-1 secretion induced by such Gq + Gs GPR40 agonists is indeed inhibited by blockers of both Gq and Gs and is eliminated by combining these. This in contrast to Gq-only GPR40 agonists which only are affected by the Gq inhibitor. Importantly, Gq-only GPR40 agonists in combination with low doses of selective synthetic agonists for Gs coupled receptors, e...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908822/how-admission-to-a-vascular-surgery-department-improves-medical-treatment-in-patients-with-lower-extremity-peripheral-arterial-disease
#10
M Thiney, N Della Schiava, P Feugier, P Lermusiaux, J Ninet, A Millon, A Long
OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the number of patients who received best medical treatment at admission and at discharge from a vascular surgery department...
November 28, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27908768/acute-stress-diminishes-m-current-contributing-to-elevated-activity-of-hypothalamic-pituitary-adrenal-axis
#11
Jing-Jing Zhou, Yonggang Gao, Therese A Kosten, Zongmao Zhao, De-Pei Li
Acute stress stimulates corticotrophin-releasing hormone (CRH)-expressing neurons in the hypothalamic paraventricular nucleus (PVN), which is an essential component of hypothalamic-pituitary-adrenal (HPA) axis. However, the cellular and molecular mechanisms remain unclear. The M-channel is a voltage-dependent K(+) channel involved in stabilizing the neuronal membrane potential and regulating neuronal excitability. In this study, we tested our hypothesis that acute stress suppresses expression of Kv7 channels to stimulate PVN-CRH neurons and the HPA axis...
November 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27906842/spironolactone-and-the-risk-of-urinary-tract-cancer-in-patients-with-hypertension-a-nationwide-population-based-retrospective-case-control-study
#12
Ya-Wen Chuang, Mei-Ching Yu, Shih-Ting Huang, Cheng-Kuang Yang, Cheng-Hsu Chen, Ying-Chih Lo, Cheng-Li Lin, Kuo-Hsiung Shu, Tung-Min Yu, Chia-Hung Kao
AIM: This was a nationwide study by National Health Insurance Research Database to investigate the risk of urinary tract cancers (UTCs) for renin-angiotensin-aldosterone system inhibitors including spironolactone. METHODS: A total of 32 167 UTC patients with hypertension were enrolled in the National Health Insurance program between 2005 and 2011. RESULTS: Among different subclasses of renin-angiotensin-aldosterone system inhibitors, the adjusted odds ratio (OR) for UTC risk was 1...
January 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/27906756/optic-neuritis-the-eye-as-a-window-to-the-brain
#13
Thomas M Jenkins, Ahmed T Toosy
PURPOSE OF REVIEW: Acute optic neuritis is a common clinical problem, requiring a structured assessment to guide management and prevent visual loss. The optic nerve is the most accessible part of the central nervous system, so optic neuritis also represents an important paradigm to help decipher mechanisms of damage and recovery in the central nervous system. Important developments include the advent of optical coherence tomography as a biomarker of central nervous system axonal loss, the discovery of new pathological antibodies, notably against aquaporin-4 and, more recently, myelin oligodendrocyte protein, and emerging evidence for sodium channel blockade as a novel therapeutic approach to address energy failure in neuroinflammatory disease...
November 30, 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27906705/arterial-pressure-variation-in-elective-noncardiac-surgery-identifying-reference-distributions-and-modifying-factors
#14
Michael R Mathis, Samuel A Schechtman, Milo C Engoren, Amy M Shanks, Aleda Thompson, Sachin Kheterpal, Kevin K Tremper
BACKGROUND: Assessment of need for intravascular volume resuscitation remains challenging for anesthesiologists. Dynamic waveform indices, including systolic and pulse pressure variation, are demonstrated as reliable measures of fluid responsiveness for mechanically ventilated patients. Despite widespread use, real-world reference distributions for systolic and pulse pressure variation values have not been established for euvolemic intraoperative patients. The authors sought to establish systolic and pulse pressure variation reference distributions and assess the impact of modifying factors...
December 1, 2016: Anesthesiology
https://www.readbyqxmd.com/read/27906696/medical-therapy-refractory-chronic-rhinosinusitis-and-productivity-costs
#15
Kristine A Smith, Luke Rudmik
PURPOSE OF REVIEW: The purpose of this review is to address the most recent advances in the medical therapy for chronic rhinosinusitis (CRS), define recalcitrant and refractory CRS, and discuss the productivity costs associated with CRS. RECENT FINDINGS: Recent studies evaluating anti-IL-4 receptor α antibodies and calcium channel blockers have demonstrated promising early results during management of CRS. Recent appropriateness criteria have been developed to assist clinicians with defining which patients have 'refractory' CRS and may be considered candidates for endoscopic sinus surgery...
November 30, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27906047/propranolol-and-survival-from-breast-cancer-a-pooled-analysis-of-european-breast-cancer-cohorts
#16
Chris R Cardwell, Anton Pottegård, Evelien Vaes, Hans Garmo, Liam J Murray, Chris Brown, Pauline A J Vissers, Michael O'Rorke, Kala Visvanathan, Deirdre Cronin-Fenton, Harlinde De Schutter, Mats Lambe, Des G Powe, Myrthe P P van Herk-Sukel, Anna Gavin, Søren Friis, Linda Sharp, Kathleen Bennett
BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network...
December 1, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27905561/anti-hu-antibodies-activate-enteric-and-sensory-neurons
#17
Qin Li, Klaus Michel, Anita Annahazi, Ihsan E Demir, Güralp O Ceyhan, Florian Zeller, Lars Komorowski, Winfried Stöcker, Michael J Beyak, David Grundy, Gianrico Farrugia, Roberto De Giorgio, Michael Schemann
IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904672/t3-inhibits-the-calcification-of-vascular-smooth-muscle-cells-and-the-potential-mechanism
#18
Xiaodan Chang, Baohong Zhang, Li Lihua, Zhichun Feng
OBJECTIVE: This study aimed to investigate the potential molecular mechanism underlying the T3 induced vascular calcification and phenotype transformation of vascular smooth muscle cells (VSMCs). METHODS: Rat thoracic aortic smooth muscle cells (A7r5) were cultured in vitro and randomly assigned into normal control group, calcification group, T3 group and inhibitor group. RESULTS: When compared with normal control group, the osteocalcin content, ALP activity, Osterix and Runx2 mRNA expression and OPN protein expression increased significantly (P<0...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904663/t-type-calcium-channel-blocker-attenuates-unilateral-ureteral-obstruction-induced-renal-interstitial-fibrosis-by-activating-the-nrf2-antioxidant-pathway
#19
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Hye Eun Yoon, Ho-Shik Kim, Cheol Whee Park, Yoon Sik Chang, Seok Joon Shin
Besides its effect on high blood pressure, T-type calcium channel blocker is renoprotective in experimental models of renal fibrosis. However, the exact mechanism of T-type calcium channel blocker on tubulointerstitial fibrosis is unclear. We investigated whether the renoprotective effect of T-type calcium channel blocker is associated with modulation of the signaling of oxidative stress-induced renal fibrosis. Treatment with a non-hypotensive dose of efonidipine, a T-type calcium channel blocker, or nifedipine, an L-type channel blocker, was initiated one day before unilateral ureteral obstruction (UUO) in C57BL6/J mice, and was continued until 3 and 7 days after UUO...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904156/effects-of-calcium-channel-blocker-benidipine-based-combination-therapy-on-target-blood-pressure-control-and-cardiovascular-outcome-a-sub-analysis-of-the-cope-trial
#20
Seiji Umemoto, Toshio Ogihara, Masunori Matsuzaki, Hiromi Rakugi, Yasuo Ohashi, Takao Saruta
We compared three benidipine-based regimens-that is, benidipine plus angiotensin receptor blocker (ARB), β-blocker (BB) or thiazide-and found that the benidipine-BB combination was less beneficial in reducing the risk of stroke than the benidipine-thiazide combination. This sub-analysis sought to compare the effects of reaching a target blood pressure (BP) (<140/90 mm Hg) on the cardiovascular outcomes among the three benidipine-based treatment groups in the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial...
December 1, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
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