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https://www.readbyqxmd.com/read/28938563/a-novel-immunotherapy-targeting-mmp-14-limits-hypoxia-immune-suppression-and-metastasis-in-triple-negative-breast-cancer-models
#1
Binbing Ling, Kathleen Watt, Sunandan Banerjee, Daniel Newsted, Peter Truesdell, Jarrett Adams, Sachdev S Sidhu, Andrew W B Craig
Matrix metalloproteinase-14 (MMP-14) is a clinically relevant target in metastatic cancers due to its role in tumor progression and metastasis. Since active MMP-14 is localized on the cell surface, it is amenable to antibody-mediated blockade in cancer, and here we describe our efforts to develop novel inhibitory anti-MMP-14 antibodies. A phage-displayed synthetic humanized Fab library was screened against the extracellular domain of MMP-14 and a panel of MMP14-specific Fabs were identified. A lead antibody that inhibits the catalytic domain of MMP-14 (Fab 3369) was identified and treatment of MDA-MB-231 breast cancer cells with Fab 3369 led to significant loss of extracellular matrix degradation and cell invasion abilities...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938542/the-immune-checkpoint-molecule-v-set-ig-domain-containing-4-is-an-independent-prognostic-factor-for-multiple-myeloma
#2
Jin Roh, Youkyoung Jeon, A-Neum Lee, Sang Min Lee, YeonMee Kim, Chang Ohk Sung, Chan-Jeoung Park, Jung Yong Hong, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh, Inhak Choi, Chan-Sik Park
Multiple myeloma (MM) remains as an incurable disease, despite recent substantial improvements in treatment. Therefore, development of novel biomarkers for risk stratification and new therapeutic targets are imperative. One of the emerging treatments for MM is the immune checkpoint blockades. V-set Ig domain-containing 4 (VSIG4) is a lately studied B7-related immune checkpoint modulator. We assessed the VSIG4 expression in patients with MM and its prognostic impact. We analyzed 81 bone marrow and 66 extramedullary biopsy samples of MM patients using immunohistochemistry...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938426/a-sustained-activation-of-pancreatic-nmdars-is-a-novel-factor-of-%C3%AE-cell-apoptosis-and-dysfunction
#3
Xiao-Ting Huang, Shao-Jie Yue, Chen Li, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Hong Li, Cai-Xia Hao, Ling-Zhi Wang, Jian-Ping Xu, Ming Ji, Chen Chen, Dan-Dan Feng, Zi-Qiang Luo
Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-D-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells...
September 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938160/nilotinib-enhances-tumor-angiogenesis-and-counteracts-vegfr2-blockade-in-an-orthotopic-breast-cancer-xenograft-model-with-desmoplastic-response
#4
Sara Zafarnia, Jessica Bzyl-Ibach, Igor Spivak, Yongping Li, Susanne Koletnik, Dennis Doleschel, Anne Rix, Sibylle Pochon, Isabelle Tardy, Seena Koyadan, Marc van Zandvoort, Moritz Palmowski, Fabian Kiessling, Wiltrud Lederle
Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted therapies predominantly affect nascent, immature tumor vessels. Since platelet-derived growth factor receptor (PDGFR) blockade inhibits vessel maturation and thus increases the amount of immature tumor vessels, we evaluated whether the combined PDGFR inhibition by nilotinib and VEGFR2 blockade by DC101 has synergistic therapy effects in a desmoplastic breast cancer xenograft model. In this context, besides immunohistological evaluation, molecular ultrasound imaging with BR55, the clinically used VEGFR2-targeted microbubbles, was applied to monitor VEGFR2-positive vessels noninvasively and to assess the therapy effects on tumor angiogenesis...
September 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28938090/small-molecule-targets-in-immuno-oncology
#5
REVIEW
Dashyant Dhanak, James P Edwards, Ancho Nguyen, Peter J Tummino
Advances in understanding the role and molecular mechanisms underlying immune surveillance and control of (pre)malignancies is revolutionizing clinical practice in the treatment of cancer. Presently, multiple biologic drugs targeting the immune checkpoint proteins PD(L)1 or CTLA4 have been approved and/or are in advanced stages of clinical development for many cancers. In addition, combination therapy with these agents and other immunomodulators is being intensively explored with the aim of improving primary response rates or prolonging overall survival...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28937963/ki67-and-lymphocytes-in-the-pretherapeutic-core-biopsy-of-primary-invasive-breast-cancer-positive-markers-of-therapy-response-prediction-and-superior-survival
#6
REVIEW
Claus M Schlotter, Lothar Tietze, Ulf Vogt, Carlos Villena Heinsen, Antje Hahn
Background Core needle biopsy plays a crucial role as diagnostic tool for BC. Both Ki67 and likely tumor-infiltrating lymphocytes (TILs) in the near future are determining the kind of systemic therapy. The role of TILs in BC is still an issue for clinical research, albeit preliminary results of neoadjuvant and adjuvant clinical studies already now highlight the crucial impact of TILs on therapy response and survival. Methods Evaluation of related publications (pubmed) and meeting abstracts (ASCO, SABCS). Results The monoclonal antibody Ki67 recognizing a nuclear antigene in proliferating cells is a positive marker of therapy response and superior survival...
September 22, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28937530/effects-of-magnesium-chloride-on-rocuronium-induced-neuromuscular-blockade-and-sugammadex-reversal-in-an-isolated-rat-phrenic-nerve-hemidiaphragm-preparation-an-in-vitro-study
#7
Tae-Yun Sung, Hwang-Ju You, Choon-Kyu Cho, Hey Ran Choi, Yong Beom Kim, Yong Sup Shin, Hong Seuk Yang
BACKGROUND: Magnesium potentiates the effects of nondepolarising muscle relaxants. However, few studies have used magnesium chloride (MgCl2). Sugammadex reverses neuromuscular block by steroidal nondepolarising muscle relaxants. OBJECTIVES: To assess the effects of MgCl2 on rocuronium-induced neuromuscular blockade and its reversal by sugammadex. DESIGN: In-vitro experimental study. SETTING: Animal laboratory, Asan Medical Center, Seoul, South Korea, from 20 March 2016 to 3 April 2016...
September 20, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28937323/clinical-characteristics-and-temporal-profile-of-recovery-in-patients-with-favorable-outcomes-at-6-months-after-severe-traumatic-brain-injury
#8
Aditya Vedantam, Claudia S Robertson, Shankar P Gopinath
OBJECTIVE Early withdrawal of life-sustaining treatment due to expected poor prognosis is responsible for the majority of in-house deaths in severe traumatic brain injury (TBI). With increased focus on the decision and timing of withdrawal of care in patients with severe TBI, data on early neurological recovery in patients with a favorable outcome is needed to guide physicians and families. METHODS The authors reviewed prospectively collected data obtained in 1241 patients with head injury who were treated between 1986 and 2012...
September 22, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28937244/cardiac-at1-receptor-dependent-and-igf1-receptor-independent-signaling-is-activated-by-a-single-bout-of-resistance-exercise
#9
S Fs Melo, V G Barauna, T Fernandes, E C Carmo, C Ro Carvalho, E M Oliveira
AT1 receptor (AT1R) blockade prevents physiological cardiac hypertrophy induced by resistance training. Also, our group showed that a single bout of resistance exercise (RE) activates the AKT/mTOR which was also inhibited by AT1R blocker. Here, we investigated whether IGF1-receptor (IGF1-R) and MAPKs were also activated after a single bout of RE. Wistar rats were divided into Sedentary (SED); Sedentary treated with losartan (SED+LOS); Exercise (EX); and Exercise treated with losartan (EX+LOS). Cardiac tissue was obtained 5 and 30 minutes after 4 sets of 12 repetitions of squat exercise (80%1RM)...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28936612/endotracheal-intubation-ultrasound-guided-versus-fiberscope-in-patients-with-cervical-spine-immobilization
#10
Moustafa Abdelaziz Moustafa, Emad A Arida, Ola M Zanaty, Sameh Fathy El-Tamboly
BACKGROUND: Ultrasound has growing applications in airway management during anesthesia. The aim of the present study was to evaluate the feasibility of real-time ultrasound-guided tracheal intubation in patients with cervical spine immobilization relative to fiberscope-guided tracheal intubation. PATIENTS AND METHODS: This randomized controlled study was carried out on 266 adult patients who have a rigid neck collar in place for cervical spine immobilization and were randomly allocated into two equal groups...
September 21, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28936405/chemotherapy-for-hepatocellular-carcinoma-current-evidence-and-future-perspectives
#11
REVIEW
Emanuele Rinninella, Lucia Cerrito, Irene Spinelli, Marco Cintoni, Maria Cristina Mele, Maurizio Pompili, Antonio Gasbarrini
Hepatocarcinogenesis is a multistep process, heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis. Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways. As hepatocellular carcinoma has higher arterial vascularization than normal liver, this could be a good target for novel molecular therapies. Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor...
September 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28935774/immunotherapy-a-new-and-old-approach-to-treatment-of-soft-tissue-and-bone-sarcomas
#12
REVIEW
Michael J Nathenson, Anthony P Conley, Edward Sausville
Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long-term survival is still low for high-risk soft tissue sarcoma patients. New treatment strategies are needed. Immunotherapy offers a new potential treatment paradigm with great promise. Immunotherapy of soft tissue sarcomas dates back to Dr. Coley's first use of toxins in the late 1800s. A variety of strategies of immunotherapy have been tried in soft tissue and bone sarcomas, including various vaccines and cytokines, with limited success...
September 21, 2017: Oncologist
https://www.readbyqxmd.com/read/28935683/synaptic-activation-of-putative-sensory-neurons-by-hexamethonium-sensitive-nerve-pathways-in-mouse-colon
#13
Timothy James Hibberd, Lee Travis, Lukasz Wiklendt, Marcello C Costa, Simon J H Brookes, Hongzhen Hu, Damien John Keating, Nick J Spencer
The gastrointestinal tract contains its own independent population of sensory neurons within the gut wall. These sensory neurons have been referred to as intrinsic primary afferent neurons (IPANs) and can be identified by immunoreactivity to calcitonin gene related peptide (CGRP) in mice. A common feature of IPANs is a paucity of fast synaptic inputs observed during sharp microelectrode recordings. Whether this is observed using different recording techniques is of particular interest for understanding the physiology of these neurons and neural circuit modelling...
September 21, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28935506/endothelial-specific-sirt3-deletion-impairs-glycolysis-and-angiogenesis-and-causes-diastolic-dysfunction
#14
Xiaochen He, Heng Zeng, Sean T Chen, Richard J Roman, Judy L Aschner, Sean Didion, Jian-Xiong Chen
Endothelial glycolysis plays a critical role in the regulation of angiogenesis. We investigated the role of Sirtuin 3 (SIRT3) on endothelial cell (EC) glycolytic metabolism, angiogenesis, and diastolic function. Our aim was to test the hypothesis that loss of SIRT3 in ECs impairs endothelial glycolytic metabolism and angiogenesis and contributes to myocardial capillary rarefaction and the development of diastolic dysfunction. Using SIRT3 deficient ECs, SIRT3 was found to regulate a metabolic switch between mitochondrial respiration and glycolysis...
September 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28935250/engineered-cells-for-costimulatory-enhancement-combined-with-il-21-enhance-the-generation-of-pd-1-disrupted-ctls-for-adoptive-immunotherapy
#15
Jie Shao, Qiuping Xu, Shu Su, Fanyan Meng, Zhengyun Zou, Fangjun Chen, Juan Du, Xiaoping Qian, Baorui Liu
Blockade of the immune cell checkpoint inhibitors programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a powerful tool in cancer treatment, which is effective across various solid cancer types and hematologic malignancies. Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) modified cytotoxic T lymphocytes (CTLs) rank highly in terms of immune responses and cytotoxicity. In this study, a genetically modified K562 cell line with surface expression of 4-1BBL was developed to expand PD-1-disrupted CTLs in vitro for further adoptive immunotherapy against cancer...
September 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28935156/activation-of-il-17-receptor-leads-to-increased-oxidative-inflammation-in-peripheral-monocytes-of-autistic-children
#16
Ahmed Nadeem, Sheikh F Ahmad, Sabry M Attia, Saleh A Bakheet, Naif O Al-Harbi, Laila Y Al-Ayadhi
Millions of children are affected by different neurodevelopmental disorders, out of which autismspectrum disorder (ASD) poses a major hurdle to normal life style due to associated behavioral abnormalities. Several studies have shown an increased expression/release of Th17 related cytokine, IL-17A in ASD. IL-17A may enhance neuroinflammation via its IL-17A receptor, i.e. IL-17RA expressed in immune cells (such as monocytes) of autistic children. Increased oxidative stress has been implicated in a number of neuropsychiatric disorders including ASD...
September 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28934781/posture-influences-the-extent-of-spread-of-contrast-medium-during-thoracic-epidurography-a-prospective-randomized-trial
#17
Ji Hee Hong, Sung Won Jung, Ji Hoon Park
BACKGROUND: Various factors influencing the distribution of sensory blockade in epidural anesthesia have been identified; however, reports on the effects of gravity and different postures in thoracic epidural anesthesia have been rare. Medications may be injected with the lateral decubitus or the neutral position; however, it is unclear whether the distribution range of medication is similar or significantly different between these 2 postures. OBJECTIVE: We focused on identifying the effect of different postures on the distribution of local anesthetics using epidurography at the thoracic level...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#18
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934376/managing-menopausal-symptoms-and-associated-clinical-issues-in-breast-cancer-survivors
#19
Richard J Santen, Cynthia A Stuenkel, Susan R Davis, JoAnn V Pinkerton, Anne Gompel, Mary Ann Lumsden
Objective: Review evidence to guide the management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly. Evidence: Randomized controlled clinical trials, observational studies, evidence- based guidelines, and expert opinion from professional societies. Background: Several symptoms and clinical problems associated with estrogen depletion -sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia and osteoporosis- confront the estimated 9...
August 2, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28934318/identification-of-lag3-high-affinity-aptamers-by-ht-selex-and-conserved-motif-accumulation-cma
#20
Mario Martínez Soldevilla, Sandra Hervas, Helena Villanueva, Teresa Lozano, Obdulia Rabal, Julen Oyarzabal, Juan José Lasarte, Maurizio Bendandi, Susana Inoges, Ascensión López-Díaz de Cerio, Fernando Pastor
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases...
2017: PloS One
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