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https://www.readbyqxmd.com/read/28329532/idiopathic-scleredema
#1
Elise Ng, Rachel Rosenstein, Vitaly Terushkin, Shane Meehan, Miriam Keltz Pomeranz
Scleredema, which also is known as scleredemaadultorum of Buschke, is an uncommonsclerodermiform condition that is characterizedby progressive thickening and hardening of theskin due to excessive dermal mucin and collagendeposition. The clinical course is variable, andprogression of disease may lead to functionalimpairment with limitations in mobility. The etiologyand pathogenesis are unknown although severalwell-known associations include streptococcalinfection; diabetes mellitus, particularly withmetabolic syndrome; and monoclonal gammopathy...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329405/a-review-of-guselkumab-an-il-23-inhibitor-for-moderate-to-severe-plaque-psoriasis
#2
Z Nawas, M Hatch, E Ramos, M Liu, Y Tong, A Peranteau, S Tyring
Psoriasis is a chronic inflammatory skin disorder that affects 2% of the population. Evidence suggests that interleukin (IL)-23 plays a pivotal role in the pathogenesis of psoriasis. Guselkumab is a subcutaneously administered, humanized anti-IL23 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. Data from Phase I-III trials in this patient population reveal that guselkumab has proven to be superior to placebo or adalimumab based on achieving a Psoriasis Area and Severity Index (PASI) 90% reduction, or a static Physician Global Assessment (sPGA) score of 0 or 1 from baseline...
March 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28329114/pcsk9-monoclonal-antibodies-reverse-the-pro-inflammatory-profile-of-monocytes-in-familial-hypercholesterolaemia
#3
Sophie J Bernelot Moens, Annette E Neele, Jeffrey Kroon, Fleur M van der Valk, Jan Van den Bossche, Marten A Hoeksema, Renate M Hoogeveen, Johan G Schnitzler, Marie T Baccara-Dinet, Garen Manvelian, Menno P J de Winther, Erik S G Stroes
Aims: Migration of monocytes into the arterial wall contributes to arterial inflammation and atherosclerosis progression. Since elevated low-density lipoprotein cholesterol (LDL-C) levels have been associated with activation of plasma monocytes, intensive LDL-C lowering may reverse these pro-inflammatory changes. Using proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) which selectively reduce LDL-C, we studied the impact of LDL-C lowering on monocyte phenotype and function in patients with familial hypercholesterolaemia (FH) not using statins due to statin-associated muscle symptoms...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28328676/correlation-between-factor-f-xia-fixa-and-tissue-factor-and-trauma-severity
#4
Shannon M Prior, Mitchell J Cohen, Amanda S Conroy, Mary F Nelson, Lucy Z Kornblith, Benjamin M Howard, Saulius Butenas
BACKGROUND: It has been observed that trauma patients often display elevated procoagulant activity that could be caused, in part, by tissue factor (TF). We previously observed that trauma patients with thermal, blunt and penetrating injuries have active FIXa and FXIa in their plasma. In the current study we evaluated the effect of injury severity, with or without accompanying shock, on the frequency and concentration of TF, FIXa and FXIa in plasma from trauma patients. METHODS: Eighty trauma patients were enrolled and divided equally into 4 groups based on their injury severity score (ISS) and base deficit (BD):Group 1: Non-severe injury, no shockGroup 2: Non-severe injury, with shockGroup 3: Severe injury, no shockGroup 4: Severe injury, with shockBlood was collected at a 0 time-point (first blood draw upon arrival at hospital) and citrate plasma was prepared, frozen and stored at -80C...
March 21, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28328624/long-term-maintenance-of-clinical-endoscopic-and-radiographic-response-to-ustekinumab-in-moderate-to-severe-crohn-s-disease-real-world-experience-from-a-multicenter-cohort-study
#5
Christopher Ma, Richard N Fedorak, Gilaad G Kaplan, Levinus A Dieleman, Shane M Devlin, Nathan Stern, Karen I Kroeker, Cynthia H Seow, Yvette Leung, Kerri L Novak, Brendan P Halloran, Vivian W Huang, Karen Wong, Philip K Blustein, Subrata Ghosh, Remo Panaccione
BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins 12 and 23. While effective in clinical trials for Crohn's disease (CD), long-term maintenance of response in the real-world setting is unclear. We aim to assess the efficacy of ustekinumab for maintaining clinical, endoscopic, and radiographic response in CD. METHODS: A retrospective multicenter cohort study was performed on patients with CD achieving steroid-free clinical response to ustekinumab induction, and advanced onto a regularly scheduled maintenance ustekinumab regimen between 2011 and 2016...
March 21, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#6
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28328036/use-of-a-stable-isotope-labeled-reporter-peptide-and-antioxidants-for-reliable-quantification-of-methionine-oxidation-in-a-monoclonal-antibody-by-liquid-chromatography-mass-spectrometry
#7
Pilsoo Kang, Tanya Mezhebovsky, Wei Chen, James A McCardle, Sheng Zhang, Eric P Sullivan, Philip M Sass, Eric Routhier
RATIONALE: Accurate quantification of methionine oxidation in therapeutic proteins by liquid chromatography/mass spectrometry (LC/MS) is challenging due to the potential artifacts introduced during sample preparation and analysis in the peptide mapping workflow. In this study, a systematic approach for optimization of the peptide mapping procedure to achieve reliable quantification of endogenous methionine oxidation in monoclonal antibodies was developed. METHODS: The approach is based on usage of a stable-isotope-labeled reporter peptide, identical in sequence to the tryptic peptide of an IgG1 monoclonal antibody containing the methionine residue most prone to oxidation...
July 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28328015/pcsk9-inhibitor-access-barriers-issues-and-recommendations-improving-the-access-process-for-patients-clinicians-and-payers
#8
REVIEW
Seth J Baum, Peter P Toth, James A Underberg, Paul Jellinger, Joyce Ross, Katherine Wilemon
The proprotein convertase subtilisin/kexin type 9 inhibitors or monoclonal antibodies likely represent the greatest advance in lipid management in 30 years. In 2015 the US Food and Drug Administration approved both alirocumab and evolocumab for high-risk patients with familial hypercholesterolemia (FH) and clinical atherosclerotic cardiovascular disease requiring additional lowering of low-density lipoprotein cholesterol. Though many lipid specialists, cardiovascular disease prevention experts, endocrinologists, and others prescribed the drugs on label, they found their directives denied 80% to 90% of the time...
March 22, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28327200/a-first-in-human-phase-1-study-of-a-hepcidin-monoclonal-antibody-ly2787106-in-cancer-associated-anemia
#9
Saroj Vadhan-Raj, Rafat Abonour, Jonathan W Goldman, David A Smith, Christopher A Slapak, Robert L Ilaria, Ramon V Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L Tuttle, Yiu-Keung Lau, Eric J Roeland
BACKGROUND: Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28326566/systematic-review-with-meta-analysis-comparative-efficacy-of-biologics-for-induction-and-maintenance-of-mucosal-healing-in-crohn-s-disease-and-ulcerative-colitis-controlled-trials
#10
REVIEW
A Cholapranee, G S Hazlewood, G G Kaplan, L Peyrin-Biroulet, A N Ananthakrishnan
BACKGROUND: Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. AIM: To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC...
March 22, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28326559/a-phase-1-study-to-evaluate-the-safety-and-ldl-cholesterol-lowering-effects-of-rg7652-a-fully-human-monoclonal-antibody-against-proprotein-convertase-subtilisin-kexin-type-9
#11
Amos Baruch, Diana Luca, Robert S Kahn, Kyra J Cowan, Maya Leabman, Nageshwar R Budha, Cecilia P C Chiu, Yan Wu, Daniel Kirchhofer, Andrew Peterson, John C Davis, Whittemore G Tingley
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates low-density lipoprotein (LDL) receptors, thereby leading to a rise in circulating LDL cholesterol (LDL-C). RG7652 is a fully human monoclonal antibody against PCSK9. This placebo-controlled, phase 1 ascending-dose study in healthy subjects evaluated the safety of RG7652 and its efficacy as a potential LDL-C-lowering drug. HYPOTHESIS: Anti-PCSK9 antibody therapy safely and effectively reduces LDL-C...
March 22, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28326356/effect-of-four-monthly-doses-of-a-human-monoclonal-anti-fgf23-antibody-krn23-on-quality-of-life-in-x-linked-hypophosphatemia
#12
Mary D Ruppe, Xiaoping Zhang, Erik A Imel, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Munro Peacock, Thomas O Carpenter
X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). OBJECTIVE: Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28326191/global-histone-modification-fingerprinting-in-human-cells-using-epigenetic-reverse-phase-protein-array
#13
Marina Partolina, Hazel C Thoms, Kenneth G MacLeod, Giovanny Rodriguez-Blanco, Matthew N Clarke, Anuroop V Venkatasubramani, Rima Beesoo, Vladimir Larionov, Vidushi S Neergheen-Bhujun, Bryan Serrels, Hiroshi Kimura, Neil O Carragher, Alexander Kagansky
The balance between acetylation and deacetylation of histone proteins plays a critical role in the regulation of genomic functions. Aberrations in global levels of histone modifications are linked to carcinogenesis and are currently the focus of intense scrutiny and translational research investments to develop new therapies, which can modify complex disease pathophysiology through epigenetic control. However, despite significant progress in our understanding of the molecular mechanisms of epigenetic machinery in various genomic contexts and cell types, the links between epigenetic modifications and cellular phenotypes are far from being clear...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28326189/sarilumab-improves-patient-reported-outcomes-in-rheumatoid-arthritis-patients-with-inadequate-response-intolerance-to-tumour-necrosis-factor-inhibitors
#14
Vibeke Strand, Matthew Reaney, Chieh-I Chen, Clare W J Proudfoot, Sophie Guillonneau, Deborah Bauer, Erin Mangan, Neil M H Graham, Hubert van Hoogstraten, Yong Lin, César Pacheco-Tena, Roy Fleischmann
OBJECTIVE: To evaluate effects of the anti-interleukin-6 receptor monoclonal antibody sarilumab administered with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on patient-reported outcomes (PROs) in the TARGET trial in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitors (TNF-IR). METHODS: 546 patients (81.9% female, mean age 52.9 years) were randomised to placebo, sarilumab 150 or 200 mg subcutaneously every 2 weeks + csDMARDs...
2017: RMD Open
https://www.readbyqxmd.com/read/28326151/chronic-porphyromonas-gingivalis-infection-accelerates-the-occurrence-of-age-related-granules-in-apoe-mice-brains
#15
Sim K Singhrao, Sasanka Chukkapalli, Sophie Poole, Irina Velsko, St John Crean, Lakshmyya Kesavalu
This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE(-/-)) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P...
2017: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/28325282/dna-aptamers-for-the-characterization-of-histological-structure-of-lung-adenocarcinoma
#16
Galina S Zamay, Tatiana I Ivanchenko, Tatiana N Zamay, Valentina L Grigorieva, Yury E Glazyrin, Olga S Kolovskaya, Irina V Garanzha, Andrey A Barinov, Alexey V Krat, Gleb G Mironov, Ana Gargaun, Dmitry V Veprintsev, Sergey S Bekuzarov, Andrey K Kirichenko, Ruslan A Zukov, Marina M Petrova, Andrey A Modestov, Maxim V Berezovski, Anna S Zamay
Nucleic acid aptamers are becoming popular as molecular probes for identification and imaging pathology and, at the same time, as a convenient platform for targeted therapy. Recent studies have shown that aptamers may be effectively used for tumor characterization and as commercially available monoclonal antibodies. Here we present three DNA aptamers binding to whole transformed lung cancer tissues, including tumor cells, connective tissues, and blood vessels. Protein targets have been revealed using affinity purification followed by mass spectrometry analyses, and they have been validated using a panel of correspondent antibodies and 3D imaging of tumor tissues...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325256/how-have-evolutions-in-strategies-for-the-treatment-of-relapsed-refractory-multiple-myeloma-translated-into-improved-outcomes-for-patients
#17
REVIEW
Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28325214/antibody-based-cancer-therapy-successful-agents-and-novel-approaches
#18
D Hendriks, G Choi, M de Bruyn, V R Wiersma, E Bremer
Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as rituximab (1997) and cetuximab (2004), and infliximab (2002) for the treatment of autoimmune diseases. More recently, the development of antibodies that prevent checkpoint-mediated inhibition of T cell responses invigorated the field of cancer immunotherapy...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28324750/biological-mechanisms-of-immune-escape-and-implications-for-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#19
REVIEW
Jennifer D Moy, Jessica M Moskovitz, Robert L Ferris
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324281/detection-of-minimal-residual-disease-in-childhood-b-acute-lymphoblastic-leukemia-by-4-color-flowcytometry
#20
Ahmad Baraka, Laila M Sherief, Naglaa M Kamal, Shereen El Shorbagy
Monitoring of minimal residual disease (MRD) is currently considered the most powerful predictor of outcome in acute lymphoblastic leukemia (ALL). Achievement of a negative MRD state assessed by multicolor flowcytometry (MFC) is an important predictor of disease-free survival (DFS) and overall survival (OS) in ALL patients. We sought to determine whether panels of antibodies combination are more suitable for detection of MRD in Childhood ALL. Eighty-four (84) patients with ALL (B-lineage subtype) were enrolled in this study...
March 21, 2017: International Journal of Hematology
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