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https://www.readbyqxmd.com/read/28749573/il-6-stat3-signaling-as-a-promising-target-to-improve-the-efficacy-of-cancer-immunotherapy
#1
REVIEW
Hidemitsu Kitamura, Yosuke Ohno, Yujiro Toyoshima, Junya Ohtake, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi
Overcoming the immunosuppressive state in tumor microenvironments is a critical issue to improve the efficacy of cancer immunotherapy. Interleukin (IL)-6, a pleiotropic cytokine, is highly produced in the tumor-bearing host. Previous studies have indicated that IL-6 suppresses the antigen presentation ability of dendritic cells (DCs) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL-6/STAT3 signaling cascade on human DCs and the subsequent induction of antitumor T cell immune responses...
July 27, 2017: Cancer Science
https://www.readbyqxmd.com/read/28749570/hepatocyte-derived-exosomes-promote-t-follicular-regulatory-cell-expansion-during-hcv-infection
#2
Dustin A Cobb, Lucy Golden-Mason, Hugo R Rosen, Young S Hahn
Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T cell responses, yet CD4(+) T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody-producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion...
July 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28749094/superiority-of-ultrasound-guided-shamrock-lumbar-plexus-block
#3
Martin V Nielsen, Thomas F Bendtsen, Jens Børglum
BACKGROUND: Ultrasound-guided lumbar plexus block performed with the Shamrock approach has received much interest since the technique was first described in 2013. The technique is believed to be faster and easier to perform and possibly safer in regards to potential complications compared with other lumbar plexus blocks. METHODS: In order to outline some favorable characteristics of the Shamrock lumbar plexus block, we performed an exhaustive search of the current literature; even though it is rather limited...
July 26, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28747771/different-potential-of-extracellular-vesicles-to-support-thrombin-generation-contributions-of-phosphatidylserine-tissue-factor-and-cellular-origin
#4
Carla Tripisciano, René Weiss, Tanja Eichhorn, Andreas Spittler, Thomas Heuser, Michael Bernhard Fischer, Viktoria Weber
Cells release diverse types of vesicles constitutively or in response to proliferation, injury, inflammation, or stress. Extracellular vesicles (EVs) are crucial in intercellular communication, and there is emerging evidence for their roles in inflammation, cancer, and thrombosis. We investigated the thrombogenicity of platelet-derived EVs, which constitute the majority of circulating EVs in human blood, and assessed the contributions of phosphatidylserine and tissue factor exposure on thrombin generation. Addition of platelet EVs to vesicle-free human plasma induced thrombin generation in a dose-dependent manner, which was efficiently inhibited by annexin V, but not by anti-tissue factor antibodies, indicating that it was primarily due to the exposure of phosphatidylserine on platelet EVs...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747551/egfr-or-her2-inhibition-modulates-the-tumor-microenvironment-by-suppression-of-pd-l1-and-cytokines-release
#5
Koung Jin Suh, Ji Hea Sung, Jin Won Kim, Song-Hee Han, Hye Seung Lee, Ahrum Min, Mi Hyun Kang, Ji Eun Kim, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Seock-Ah Im, Jong Seok Lee
BACKGROUND: Characteristics of tumor microenvironment have been suggested as predictive markers of anti-EGFR or anti-HER2 treatment response. However, the effect of EGFR/HER2 signal blockade on the tumor immune microenvironment is unclear. METHODS: EGFR/HER2 pathway signaling and PD-L1 expression in gastric cancer cell lines were screened by western blot analysis. PD-L1 and HER2 expressions in 251 resected gastric tumors were determined by immunohistochemistry, and changes in EFGR, HER2, and PD-L1 expression in paired specimens between pre- and post-chemotherapy were evaluated...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747510/nonspecific-block-of-voltage-gated-potassium-channels-has-greater-effect-on-distal-schaffer-collaterals-than-proximal-schaffer-collaterals-during-periods-of-high-activity
#6
Benjamin Owen, Rishi Reddy, Lawrence M Grover
Previous studies established different responses between proximal and distal portions of Schaffer collateral axons during high-frequency and burst stimulation, with distal axons demonstrating biphasic changes in excitability (hyperexcitability followed by depression), but proximal axons showing only monophasic depression. Voltage-dependent potassium (KV) channels are important determinants of axonal excitability, and block of KV channels can promote axon hyperexcitability. We therefore hypothesized that block of KV channels should lead to biphasic response changes in proximal Schaffer collaterals, like those seen in distal Schaffer collaterals...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28747426/intestinal-epithelial-cell-endoplasmic-reticulum-stress-promotes-mult1-up-regulation-and-nkg2d-mediated-inflammation
#7
Shuhei Hosomi, Joep Grootjans, Markus Tschurtschenthaler, Niklas Krupka, Juan D Matute, Magdalena B Flak, Eduardo Martinez-Naves, Manuel Gomez Del Moral, Jonathan N Glickman, Mizuki Ohira, Lewis L Lanier, Arthur Kaser, Richard Blumberg
Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an unfolded protein response-related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1(ΔIEC) ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein...
July 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28747139/a-monoclonal-antibody-against-cd86-and-its-protection-in-a-murine-lupus-nephritis-model-of-chronic-graft-versus-host-disease
#8
Lianhua Han, Lijun Shen, Ying Zhu, Yuhua Qiu
CONTEXT: Lupus nephritis is the most common complication that causes the death of systemic lupus erythematosus patients. CD28/CTLA4 and their ligands CD80 or CD86 costimulatory pathway play a pivotal role in autoimmune disease and organ transplantation. OBJECTIVES: We generated a monoclonal antibody (clone 1D1) against human CD86 (1D1) that could recognize both human and mouse CD86, and blocked the CD86/CD28 costimulatory pathway with our mAb on a murine lupus nephritis model induced with chronic graft-versus-host disease (cGVHD)...
July 26, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28746398/tomosyn-associates-with-secretory-vesicles-in-neurons-through-its-n-and-c-terminal-domains
#9
Cornelia J Geerts, Roberta Mancini, Ning Chen, Frank T W Koopmans, Ka Wan Li, August B Smit, Jan R T van Weering, Matthijs Verhage, Alexander J A Groffen
The secretory pathway in neurons requires efficient targeting of cargos and regulatory proteins to their release sites. Tomosyn contributes to synapse function by regulating synaptic vesicle (SV) and dense-core vesicle (DCV) secretion. While there is large support for the presynaptic accumulation of tomosyn in fixed preparations, alternative subcellular locations have been suggested. Here we studied the dynamic distribution of tomosyn-1 (Stxbp5) and tomosyn-2 (Stxbp5l) in mouse hippocampal neurons and observed a mixed diffuse and punctate localization pattern of both isoforms...
2017: PloS One
https://www.readbyqxmd.com/read/28746269/transversus-abdominis-plane-blocks-with-single-dose-liposomal-bupivacaine-in-conjunction-with-a-nonnarcotic-pain-regimen-help-reduce-length-of-stay-following-abdominally-based-microsurgical-breast-reconstruction
#10
Eric M Jablonka, Andreas M Lamelas, Julie N Kim, Bianca Molina, Nathan Molina, Michelle Okwali, William Samson, Mark R Sultan, Joseph H Dayan, Mark L Smith
BACKGROUND: Side effects associated with use of postoperative narcotics for pain control can delay recovery after abdominally based microsurgical breast reconstruction. The authors evaluated a nonnarcotic pain control regimen in conjunction with bilateral transversus abdominis plane blocks on facilitating early hospital discharge. METHODS: A retrospective analysis was performed of consecutive patients who underwent breast reconstruction using abdominally based free flaps, with or without being included in a nonnarcotic protocol using intraoperative transversus abdominis plane blockade...
August 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28746078/spinal-microglia-are-required-for-long-term-maintenance-of-neuropathic-pain
#11
Stefania Echeverry, Xiang Qun Shi, Mu Yang, Hao Huang, YiChen Wu, Louis-Etienne Lorenzo, Jimena Perez-Sanchez, Robert P Bonin, Yves De Koninck, Ji Zhang
While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28746020/pembrolizumab-induced-pancytopenia-a-case-report
#12
Dinesh Atwal, Krishna P Joshi, Rahul Ravilla, Fade Mahmoud
INTRODUCTION: Programmed death receptor-1 blockade with pembrolizumab is approved by the US Food and Drug Administration to treat patients with metastatic melanoma. Activating T cells to fight cancer may cause immune-mediated adverse events. Pembrolizumab-induced pancytopenia has not been previously reported in the medical literature, to our knowledge. CASE PRESENTATION: A 52-year-old Caucasian woman with a diagnosis of metastatic melanoma of the rectum experienced multiple adverse events along her course of therapy with pembrolizumab, ranging from colitis, hepatitis, gastritis, and vitiligo after the fifth cycle of pembrolizumab; to knee synovitis after the 14th cycle; and to severe pancytopenia after the 18th cycle of pembrolizumab...
2017: Permanente Journal
https://www.readbyqxmd.com/read/28745931/prospect-for-immune-checkpoint-blockade-dynamic-and-comprehensive-monitorings-pave-the-way
#13
Weili Wang, Jie Liu, Yijing He, Howard L McLeod
Immune checkpoint blockade, which releases the brake of the immune system to enhance anticancer immune response, stands out in the cancer immunotherapy field due to their remarkable and long-lasting effect. However, the overall response rate for currently approved immune checkpoint inhibitors is only about 10-40%. We have summarized three major components, which are the presence of checkpoints, the immune-activation mechanism and the immune-inhibitory mechanism, containing six factors to describe the cancer-immune interaction dynamically and comprehensively, which shed light on promising biomarkers in immune checkpoint therapy...
July 26, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28745679/-low-back-pain-and-modic-changes
#14
E L Sokov, L E Kornilova, A I Nesterov
Modic changes (MCh) are pathological changes in the bone marrow and the endplates of adjacent vertebrae characterized by bone marrow edema, fatty degeneration or osteosclerosis that are revealed by high-power field magnetic resonance imaging (MRI). The dominant disease pattern is a persistent back pain syndrome with varying intensity. It leads to difficulties in the interpretation of clinical data, evaluation of MRI data and treatment. The article presents a modern conception of the pathogenesis, classification, clinical implications and treatment of MCh based on national and foreign sources as well and the author's view on the osteogenic mechanism of the pathogenesis and treatment of MCh using intraosseous blockades...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28745331/cd47-blockade-enhances-therapeutic-activity-of-tcr-mimic-antibodies-to-ultra-low-density-cancer-epitopes
#15
M D Mathias, J T Sockolosky, A Y Chang, K S Tan, C Liu, K C Garcia, D A Scheinberg
Leukemia accepted article preview online, 12 July 2017. doi:10.1038/leu.2017.223.
July 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28745057/a-nanoscale-ion-pump-derived-from-a-biological-water-channel
#16
Karl Decker, Martin Anthony Page, Aleksei Aksimentiev
Biological molecular machines perform the work of supporting life at the smallest of scales, including the work of shuttling ions across cell boundaries and against chemical gradients. Systems of artificial channels at the nanoscale can likewise control ionic concentration by way of ionic current rectification, species selectivity, and voltage gating mechanisms. Here, we theoretically show that a voltage-gated, ion species-selective and rectifying ion channel can be built using components of a biological water channel aquaporin...
July 26, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28744646/peptides-selected-using-phage-library-variants-effectively-inhibit-trypanosoma-cruzi-infection
#17
Yu E Kleshchenko, A V Zhigunova, M V Dalin, V Melnikov
Four peptide sequences characterized by high content of hydrophobic, charged, and polar amino acids were obtained from 23 clones of M13 phage. Peptides P2 and P4 exhibited highest binding affinity for immobilized trypomastigotes. The inhibitory effects of peptides seemed to be due to blockade of certain epitopes on T. cruzi surface proteins responsible for interactions with the respective receptors of host cells.
July 25, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28743359/obesity-is-the-main-determinant-of-insulin-resistance-more-than-the-circulating-pro-inflammatory-cytokines-levels-in-rheumatoid-arthritis-patients
#18
Jesus Castillo-Hernandez, Martha Imelda Maldonado-Cervantes, Juan Pablo Reyes, Nuria Patiño-Marin, Enrique Maldonado-Cervantes, Claudia Solorzano-Rodriguez, Esperanza de la Cruz Mendoza, Brenda Alvarado-Sanchez
BACKGROUND: Systemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. OBJECTIVES: To evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease...
July 2017: Revista Brasileira de Reumatologia
https://www.readbyqxmd.com/read/28743130/sglt-2-inhibition-a-potential-new-treatment-for-diabetic-kidney-disease
#19
Robert D Toto
Diabetic nephropathy is the leading cause of kidney failure. Treatments with drugs that block the renin-angiotensin system have proven beneficial in slowing kidney disease progression among those with diabetes; their benefit is limited and they do not stop disease progression. Despite multiple clinical trials of various interventions including dual blockade of the renin-angiotensin system over the past 15 years, no new therapies have emerged to slow kidney disease progression in diabetes. SGLT-2 inhibitors are a new class of antiglycemic drugs that have been shown to lower blood glucose by inhibition of the sodium-glucose transporter 2 in the proximal tubule of the kidney...
July 26, 2017: Nephron
https://www.readbyqxmd.com/read/28742984/single-versus-combined-immunoregulatory-approach-using-pd-1-and-ctla-4-modulators-in-controlling-sepsis
#20
Courtney P Rudick, David L Cornell, Devendra K Agrawal
Sepsis is a disease process characterized by an extreme inflammatory response followed by a period of severe immunosuppression. In recent years, there has been improved survival in the initial immune response during systemic inflammatory response syndrome, and compensatory anti-inflammatory response, yet is mostly unchanged with 18-30% mortality during the later stage of sepsis despite numerous Phase 3 clinical trials. Areas covered: This review article presents a critical evaluation of the most promising newer studies aimed at improving the immunosuppressive stage of sepsis...
July 25, 2017: Expert Review of Clinical Immunology
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