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https://www.readbyqxmd.com/read/28454356/harnessing-antitumor-immunity-employment-of-tumor-recall-antigens-to-optimize-the-inflammatory-response-to-cancer
#1
Kimberly A Silverio, Shyam A Patel
The advent of immunotherapy for cancer has contributed to the era of personalized medicine for cancer. The various immunotherapy-based treatments that have been explored thus far include monoclonal antibody therapy, tumor vaccines, immune checkpoint blockade and adoptive T cell transfer, among others. The groundwork for all these immunotherapeutic modalities rests within the tumor microenvironment, specifically the immune factors that influence the tumor-drug interface. Prior to therapeutic design, the tumor microenvironmental interactions and the current barriers to successful treatment must first be understood...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454342/feasibility-and-antitumor-efficacy-in-vivo-of-simultaneously-targeting-glycolysis-glutaminolysis-and-fatty-acid-synthesis-using-lonidamine-6-diazo-5-oxo-l-norleucine-and-orlistat-in-colon-cancer
#2
Diana Cervantes-Madrid, Guadalupe Dominguez-Gomez, Aurora Gonzalez-Fierro, Enrique Perez-Cardenas, Lucia Taja-Chayeb, Catalina Trejo-Becerril, Alfonso Duenas-Gonzalez
The aim of the present study was to investigate in vivo the feasibility and efficacy of the combination of lonidamine (LND), 6-diazo-5-oxo-L-norleucine (DON) and orlistat to simultaneously target glycolysis, glutaminolysis and de novo synthesis of fatty acids, respectively. The doses of LND and DON used in humans were translated to mouse doses (77.7 mg/kg and 145.5 mg/kg, respectively) and orlistat was used at 240 mg/kg. Three schedules of LND, DON and orlistat at different doses were administered by intraperitoneal injection to BALB/c mice in a 21-day cycle (schedule 1: LND, 0...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454080/relevance-of-ccl3-ccr5-axis-in-oral-carcinogenesis
#3
Janine Mayra da Silva, Tálita Pollyanna Moreira Dos Santos, Lays Martin Sobral, Celso Martins Queiroz-Junior, Milene Alvarenga Rachid, Amanda E I Proudfoot, Gustavo Pompermaier Garlet, Aline Carvalho Batista, Mauro Martins Teixeira, Andréia Machado Leopoldino, Remo Castro Russo, Tarcília Aparecida Silva
The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO)...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453838/impact-of-pre-exposure-history-and-host-genetics-on-antibody-avidity-following-norovirus-vaccination
#4
Lisa C Lindesmith, Michael L Mallory, Taylor A Jones, Charles Richardson, Robert R Goodwin, Frank Baehner, Paul M Mendelman, Robert F Bargatze, Ralph S Baric
Background.: Development of high avidity, broadly neutralizing antibodies (Abs) is a priority after vaccination against rapidly evolving, widely disseminated viruses like human norovirus. After vaccination with a multivalent GI.1 and GII.4c norovirus virus-like particle (VLP) vaccine candidate adjuvanted with alum and monophosphoryl lipid A (MPL), blockade Ab titers peaked early, with no increase in titer following a second vaccine dose. Methods.: Blockade Ab relative avidity was evaluated by measuring the slope of blockade Ab neutralization curves...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28453766/comparable-immune-function-inhibition-by-the-infliximab-biosimilar-ct-p13-implications-for-treatment-of-inflammatory-bowel-disease
#5
Ki Jung Lim, So Jung Lee, Sunghwan Kim, Su Yeon Lee, Min Seob Lee, Yoon A Park, Eun Jin Choi, Eun Beom Lee, Hwang Keun Jun, Jong Moon Cho, SooYoung Lee, Ki Sung Kwon, Byung Pil Lim, Myung-Shin Jeon, Eui Cheol Shin, Yong Sung Choi, Ella Fudim, Orit Picard, Miri Yavzori, Shomron Ben-Horin, Shin Jae Chang
Background and Aims: CT-P13 is the first biosimilar monoclonal antibody to infliximab, and was recently approved in the European Union, Japan, Korea, and USA for all six indications of infliximab. However, studies directly assessing the biologic activity of CT-P13 versus inflximab in the context of inflammatory bowel disease [IBD] are still scanty. In the present study, we aimed to compare the biological activities of CT-P13 and infliximab with specific focus on intestinal cells so as to gain insight into the potential biosimilarity of these two agents for treatment of IBD...
May 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28453552/specific-blockade-of-rictor-mtor-association-inhibits-mtorc2-activity-and-is-cytotoxic-in-glioblastoma
#6
Angelica Benavides-Serrato, Jihye Lee, Brent Holmes, Kenna A Landon, Tariq Bashir, Michael E Jung, Alan Lichtenstein, Joseph Gera
A small molecule which specifically blocks the interaction of Rictor and mTOR was identified utilizing a high-throughput yeast two-hybrid screen and evaluated as a potential inhibitor of mTORC2 activity in glioblastoma multiforme (GBM). In vitro, CID613034 inhibited mTORC2 kinase activity at submicromolar concentrations and in cellular assays specifically inhibited phosphorylation of mTORC2 substrates, including AKT (Ser-473), NDRG1 (Thr-346) and PKCα (Ser-657), while having no appreciable effects on the phosphorylation status of the mTORC1 substrate S6K (Thr-389) or mTORC1-dependent negative feedback loops...
2017: PloS One
https://www.readbyqxmd.com/read/28453392/histamine-as-an-endothelium-derived-relaxing-factor-in-aged-mesenteric-lymphatic-vessels
#7
Irina Tsoy Nizamutdinova, Daisuke Maejima, Takashi Nagai, Cynthia J Meininger, Anatoliy A Gashev
BACKGROUND: Knowledge of the mechanisms by which aging affects contracting lymphatic vessels remains incomplete; therefore, the functional role of histamine in the reaction of aged lymphatic vessels to increases in flow remains unknown. METHODS AND RESULTS: We measured and analyzed parameters of lymphatic contractility in isolated and pressurized rat mesenteric lymphatic vessels (MLVs) obtained from 9- and 24-month Fischer-344 rats under control conditions and after pharmacological blockade of nitric oxide (NO) by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μM) or/and blockade of histamine production by α-methyl-DL-histidine dihydrochloride (α-MHD, 10 μM)...
April 28, 2017: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/28449154/dual-raas-blockade-with-aliskiren-in-patients-with-severely-impaired-chronic-kidney-disease
#8
Franz Maximilian Rasche, Claudia Joel, Thomas Ebert, Thomas Frese, Filip Barinka, Volker Busch, Wilma Gertrud Rasche, Tom H Lindner, Jochen Schneider, Stephan Schiekofer
Dual renin-angiotensin-aldosterone blockade (dRAASb) is purposed in the prevention of the cardiorenal syndrome (CRS). However, all attempts with dRAASb even in patients with moderate impaired chronic kidney disease (CKD) were terminated due to the typical severe adverse events (SAE), e. g., hyperkalemia and rise of serum creatinine. The aim of our study with the direct renin inhibitor aliskiren was to evaluate the effect of dRAASb with a washout phase in patients with severely advanced CKD. We have studied 45 patients (G3b to 4, A2 and >A3; median glomerular filtration rate (GFR) CKD-EPI 31 (23-40) ml/min per 1...
April 27, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28448951/neuromuscular-blockade-requirement-is-associated-with-good-neurologic-outcome-in-cardiac-arrest-survivors-treated-with-targeted-temperature-management
#9
Dong Hun Lee, Byung Kook Lee, Kyung Woon Jeung, Yong Hun Jung, Yong Soo Cho, Chun Song Youn, Yong Il Min
PURPOSE: We examined the association between neuromuscular blockade (NMB) requirements and outcomes and lactate clearance in cardiac arrest survivors treated with targeted temperature management (TTM). METHODS: We included consecutive adult cardiac arrest survivors treated with TTM between 2012 and 2015. NMB use was categorized into 3 groups: no NMB, bolus NMB (intermittent bolus use), and continuous NMB (continuous infusion). Serum lactate levels were measured on admission and at 12h, 24h, and 48h after admission...
April 19, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28448864/new-agents-for-endocrine-resistance-in-breast-cancer
#10
REVIEW
Christian Maurer, Samuel Martel, Dimitrios Zardavas, Michail Ignatiadis
Estrogen receptor positive (ER+) and HER2-negative (HER2-) breast cancer (BC) is the most common BC subtype, defined by expression of the ER and absence of HER2 amplification. Endocrine treatment (ET), aiming at therapeutic blockade of ER signaling, represents the therapeutic mainstay for patients with both early and advanced disease. Despite its wide therapeutic efficacy, ET fails for a proportion of ER+, HER2- BC patients with early disease who develop endocrine resistance, resulting in disease recurrence...
April 24, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28448588/allogeneic-pasc-transplantation-in-humanized-pigs-attenuates-cardiac-remodeling-post-myocardial-infarction
#11
Rafael Dariolli, Marcus V Naghetini, Euclydes F Marques, Celso K Takimura, Leonardo S Jensen, Bianca Kiers, Jeane M Tsutsui, Wilson Mathias, Pedro A Lemos Neto, Jose E Krieger
Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact...
2017: PloS One
https://www.readbyqxmd.com/read/28447862/high-reliability-microcontroller-nerve-stimulator-for-assistance-in-regional-anaesthesia-procedures
#12
Carlos A Ferri, Antonio A F Quevedo
In the last decades, the use of nerve stimulators to aid in regional anaesthesia has been shown to benefit the patient since it allows a better location of the nerve plexus, leading to correct positioning of the needle through which the anaesthetic is applied. However, most of the nerve stimulators available in the market for this purpose do not have the minimum recommended features for a good stimulator, and this can lead to risks to the patient. Thus, this study aims to develop an equipment, using embedded electronics, which meets all the characteristics, for a successful blockade...
April 27, 2017: Journal of Medical Engineering & Technology
https://www.readbyqxmd.com/read/28447667/tweak-blockade-decreases-atherosclerotic-lesion-size-and-progression-through-suppression-of-stat1-signaling-in-diabetic-mice
#13
Valvanera Fernández-Laso, Cristina Sastre, Nerea Méndez-Barbero, Jesús Egido, Jose L Martín-Ventura, Carmen Gómez-Guerrero, Luis M Blanco-Colio
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK/Tnfsf12) is a cytokine implicated in different steps associated with vascular remodeling. However, the role of TWEAK under hyperglycemic conditions is currently unknown. Using two different approaches, genetic deletion of Tnfsf12 and treatment with a TWEAK blocking mAb, we have analyzed the effect of TWEAK inhibition on atherosclerotic plaque progression and stability in streptozotocin-induced diabetic ApoE deficient mice. Genetic inactivation of Tnfsf12 reduced atherosclerosis extension and severity in diabetic ApoE deficient mice...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28447099/endogenous-developmental-endothelial-locus-1-limits-ischaemia-related-angiogenesis-by-blocking-inflammation
#14
Anne Klotzsche-von Ameln, Sebastian Cremer, Jedrzej Hoffmann, Peggy Schuster, Sherif Khedr, Irina Korovina, Maria Troullinaki, Ales Neuwirth, David Sprott, Antonios Chatzigeorgiou, Matina Economopoulou, Alessia Orlandi, Andreas Hain, Andreas M Zeiher, Andreas Deussen, George Hajishengallis, Stefanie Dimmeler, Triantafyllos Chavakis, Emmanouil Chavakis
We have recently identified endothelial cell-secreted developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of β2-integrin-dependent leukocyte infiltration. Del-1 was previously also implicated in angiogenesis. Here, we addressed the role of endogenously produced Del-1 in ischaemia-related angiogenesis. Intriguingly, Del-1-deficient mice displayed increased neovascularisation in two independent ischaemic models (retinopathy of prematurity and hind-limb ischaemia), as compared to Del-1-proficient mice...
April 27, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28446951/power-spectral-density-analysis-of-purkinje-cell-tonic-and-burst-firing-patterns-from-a-rat-model-of-ataxia-and-riluzole-treated
#15
Samira Abbasi, Ataollah Abbasi, Yashar Sarbaz, Mahyar Janahmadi
INTRODUCTION: Purkinje Cell (PC) output displays a complex firing pattern consisting of high frequency sodium spikes and low frequency calcium spikes, and disruption in this firing behavior may contribute to cerebellar ataxia. Riluzole, neuroprotective agent, has been demonstrated to have neuroprotective effects in cerebellar ataxia. Here, the spectral analysis of PCs firing in control, 3-acetylpyridine (3-AP), neurotoxin agent, treated alone and riluzole plus 3-AP treated were investigated to determine changes in the firing properties...
January 2017: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/28446778/tumor-necrosis-factor-prevents-candida-albicans-biofilm-formation
#16
Francisco Airton Castro Rocha, Anelise Maria Costa Vasconcelos Alves, Marcos Fábio Gadelha Rocha, Rossana de Aguiar Cordeiro, Raimunda Sâmia Nogueira Brilhante, Ana Carolina Matias Dinelly Pinto, Rodolfo de Melo Nunes, Virgínia Cláudia Carneiro Girão, José Julio Costa Sidrim
Candida species are commensals but some develop biofilms in prosthetic materials and host surfaces that may represent up to 30% of deaths related to infections, particularly in immunosuppressed patients. Tumor necrosis factor (TNF) exhibits a plethora of functions in host defense mechanisms whereas excessive release of TNF in inflammation promotes tissue damage. Cytokines released in an inflammatory milieu may influence the development of microorganisms either by promoting their growth or displaying antimicrobial activity...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446669/salivary-blockade-protects-the-lower-respiratory-tract-of-mice-from-lethal-influenza
#17
Karen Ivinson, Georgia Deliyannis, Leanne McNabb, Lara Grollo, Brad Gilbertson, David Jackson, Lorena E Brown
It is possible to model progression of influenza virus from the upper respiratory tract to the lower respiratory tract in the mouse using viral inoculum delivered in a restricted manner to the nose. In this model, infection with the A/Udorn/307/72 (Udorn) strain of virus results ultimately in high viral titres in both the trachea and lungs. In contrast, the A/Puerto Rico/8/34 (PR8) strain causes an infection that is almost entirely limited to the nasal passages. The factors that govern the progression of virus down the respiratory tract are not well understood...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446615/proliferation-of-pd-1-cd8-t-cells-in-peripheral-blood-after-pd-1-targeted-therapy-in-lung-cancer-patients
#18
Alice O Kamphorst, Rathi N Pillai, Shu Yang, Tahseen H Nasti, Rama S Akondy, Andreas Wieland, Gabriel L Sica, Ke Yu, Lydia Koenig, Nikita T Patel, Madhusmita Behera, Hong Wu, Megan McCausland, Zhengjia Chen, Chao Zhang, Fadlo R Khuri, Taofeek K Owonikoko, Rafi Ahmed, Suresh S Ramalingam
Exhausted T cells in chronic infections and cancer have sustained expression of the inhibitory receptor programmed cell death 1 (PD-1). Therapies that block the PD-1 pathway have shown promising clinical results in a significant number of advanced-stage cancer patients. Nonetheless, a better understanding of the immunological responses induced by PD-1 blockade in cancer patients is lacking. Identification of predictive biomarkers is a priority in the field, but whether peripheral blood analysis can provide biomarkers to monitor or predict patients' responses to treatment remains to be resolved...
April 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28446581/cl-channel-is-required-for-cxcl10-induced-neuronal-activation-and-itch-response-in-a-murine-model-of-allergic-contact-dermatitis
#19
Lintao Qu, Kai Fu, Steven G Shimada, Robert H LaMotte
Persistent itch often accompanies allergic contact dermatitis (ACD), but the underlying mechanisms remain largely unexplored. We previously demonstrated that CXCL10/ CXCR3 signaling activated a subpopulation of cutaneous primary sensory neurons and mediated itch response after contact hypersensitivity (CHS), a murine model of ACD, induced by squaric acid dibutylester. The purpose of this study was to determine the ionic mechanisms underlying CXCL10-induced neuronal activation and allergic itch. In whole-cell recordings, CXCL10 triggered a current in dorsal root ganglion (DRG) neurons innervating the area of CHS...
April 26, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28446053/immunotherapy-for-the-treatment-of-breast-cancer
#20
Mariela A Moreno Ayala, Maria Florencia Gottardo, Antonela S Asad, Camila Zuccato, Alejandro Nicola, Adriana Seilicovich, Marianela Candolfi
Introduction Breast cancer is the most common cancer as well as the highest cause of death by cancer in women worldwide. Although routine treatment improves the outcome of early stage breast cancer patients, there is no effective therapy for the disseminated disease. Immunotherapy has emerged as a powerful therapeutic strategy for the treatment of many cancers. Although traditionally conceived as a non-immunogenic tumor, breast cancer is now considered a potential target for immunotherapy. Areas covered In this review, the authors discuss different immunotherapeutic strategies that are currently being tested for the treatment of breast cancer: These strategies include: (i) the blockade of immunological checkpoints, (ii) antitumor vaccines, (iii) adoptive T-cell transfer therapy, and (iv) adoptive immunotherapy with monoclonal antibodies...
April 27, 2017: Expert Opinion on Biological Therapy
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