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https://www.readbyqxmd.com/read/29045869/metastability-gap-in-the-phase-diagram-of-monoclonal-igg-antibody
#1
Jacob B Rowe, Rachel A Cancel, Tyler D Evangelous, Rhiannon P Flynn, Sergei Pechenov, J Anand Subramony, Jifeng Zhang, Ying Wang
Crystallization of IgG antibodies has important applications in the fields of structural biology, biotechnology, and biopharmaceutics. However, a rational approach to crystallize antibodies is still lacking. In this work, we report a method to estimate the solubility of antibodies at various temperatures. We experimentally determined the full phase diagram of an IgG antibody. Using the full diagram, we examined the metastability gaps, i.e., the distance between the crystal solubility line and the liquid-liquid coexistence curve, of IgG antibodies...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29045824/enhanced-doxorubicin-delivery-to-hepatocellular-carcinoma-cells-via-cd147-antibody-conjugated-immunoliposomes
#2
Jian Wang, Zhitao Wu, Guoyu Pan, Junsheng Ni, Fangyuan Xie, Beige Jiang, Lixin Wei, Jie Gao, Weiping Zhou
HAb18G/CD147, an important marker in the progression of hepatocellular carcinoma (HCC), is highly expressed on the surface of HCC cells. To increase the therapeutic efficacy of Doxil (PEGylated liposomal doxorubicin) against HCC, we constructed CD147-targeted doxorubicin-loaded immunoliposomes (Anti-CD147 ILs-DOX) by conjugating F(ab')2 of a CD147-specific monoclonal antibody to DSPE-PEG-MAL, and then inserted the antibody-conjugated polymer to Doxil. Anti-CD147 ILs-DOX delivered DOX to CD147-overexpressing HCC cells specifically and efficiently in vitro and in vivo, resulting in enhanced therapeutic effects than non-targeted controls...
October 15, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29045541/from-hepatitis-c-virus-infection-to-b-cell-lymphoma
#3
L Couronné, E Bachy, S Roulland, B Nadel, F Davi, M Armand, D Canioni, J M Michot, C Visco, L Arcaini, C Besson, O Hermine
In addition to liver disorders, Hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to anti-viral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated...
October 10, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045518/negative-hyper-selection-of-metastatic-colorectal-cancer-patients-for-anti-egfr-monoclonal-antibodies-the-pressing-case-control-study
#4
C Cremolini, F Morano, R Moretto, R Berenato, E Tamborini, F Perrone, D Rossini, A Gloghini, A Busico, G Zucchelli, C Baratelli, E Tamburini, M Tampellini, E Sensi, G Fucà, C Volpi, M Milione, M Di Maio, G Fontanini, F De Braud, A Falcone, F Pietrantonio
Background: Refining the selection of metastatic colorectal cancer (mCRC) patients candidates for anti-EGFR monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signaling pathways, have been suggested by preclinical and retrospective studies. Patients and methods: We conducted this multicenter, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations (PRESSING panel), including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions, and HER2/PI3K/PTEN/AKT1 mutations...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045436/development-and-characterization-of-novel-chimeric-monoclonal-antibodies-for-broad-spectrum-neutralization-of-rabies-virus
#5
Pan Kyeom Kim, Sun Ju Keum, Modupe O V Osinubi, Richard Franka, Ji Young Shin, Sang Tae Park, Man Su Kim, Mi Jung Park, Soo Young Lee, William Carson, Lauren Greenberg, Pengcheng Yu, Xiaoyan Tao, Wang Lihua, Qing Tang, Guodong Liang, Madhusdana Shampur, Charles E Rupprecht, Shin Jae Chang
Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody...
2017: PloS One
https://www.readbyqxmd.com/read/29045188/rapid-evolution-of-thyroid-dysfunction-in-patients-treated-with-nivolumab
#6
Grenye O'Malley, Hanna J Lee, Samir Parekh, Matthew D Galsky, Cardinale B Smith, Philip Friedlander, Robert T Yanagisawa, Emily J Gallagher
OBJECTIVE: To describe the evolution of thyroid dysfunction in a series of patients with cancer treated with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) monoclonal antibody, nivolumab. METHODS: Cases of thyroid dysfunction after initiation of checkpoint inhibitor treatment were identified from the Division of Endocrinology clinical practice at Mount Sinai Hospital, New York from April 2016 to February 2017. Charts were reviewed to identify patients treated with nivolumab with new onset of thyroid dysfunction...
October 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29044416/disease-and-region-specificity-of-granulin-immunopositivities-in-alzheimer-disease-and-frontotemporal-lobar-degeneration
#7
Qinwen Mao, Dongyang Wang, Yanqing Li, Missia Kohler, Jayson Wilson, Zachary Parton, Bella Shmaltsuyeva, Demirkan Gursel, Rosa Rademakers, Sandra Weintraub, Marek-Marsel Mesulam, Haibin Xia, Eileen H Bigio
Heterozygous loss-of-function mutations in GRN, the progranulin gene, which result in progranulin (PGRN) protein haploinsufficiency, are a major cause of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). PGRN is composed of seven and a half repeats of a highly conserved granulin motif that is cleaved to produce the granulin peptides A-G and paragranulin. To better understand the role of PGRN and granulin (Grn) peptides in the pathogenesis of neurodegeneration, we evaluated PGRN/Grn in brains of patients with Alzheimer disease, FTLD-TDP type A with or without GRN mutations, and normal individuals, using a panel of monoclonal antibodies against Grn peptides A-G...
November 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29043884/guselkumab-for-psoriasis-a-critical-appraisal-of-phase-iii-studies
#8
Zenas Zn Yiu, Richard B Warren
Biologic therapies have raised the frontiers of accepted treatment efficacy for severe psoriasis. Guselkumab is an IgG1 monoclonal antibody that binds to the p19 subunit and inhibits IL-23. In three Phase III randomized, active comparator and placebo controlled trials, guselkumab demonstrated superior efficacy and a comparable safety profile when assessed against adalimumab and ustekinumab. Critical appraisal highlighted uncertainties over risk of bias from missing details in the trial publications that would be overcome with the provision of accompanying trial protocols, as well as the need for a head-to-head trial against an IL-17 inhibitor...
October 18, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29043871/a-review-of-sarilumab-for-the-treatment-of-rheumatoid-arthritis
#9
Eun Bong Lee
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease predominantly affecting the peripheral diarthrodial joints. Sarilumab is a human monoclonal antibody against the IL-6 receptor-α. In Phase II and III clinical trials, sarilumab in the background of methotrexate showed superior clinical efficacy over placebo in RA patients with inadequate response to methotrexate or inadequate response or intolerance to TNF inhibitors. Sarilumab monotherapy also showed superior efficacy compared with adalimumab monotherapy in RA patients with inadequate response or intolerance to methotrexate...
October 18, 2017: Immunotherapy
https://www.readbyqxmd.com/read/29043461/effect-of-anti-angiogenesis-induced-by-chemotherapeutic-monotherapy-chemotherapeutic-bisphosphonate-combination-therapy-and-anti-vegfa-mab-therapy-on-tooth-extraction-socket-healing-in-mice
#10
Yuri Akita, Shinichiro Kuroshima, Kazunori Nakajima, Hiroki Hayano, Riho Kanai, Muneteru Sasaki, Takashi Sawase
Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy...
October 17, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/29043399/immunohistochemical-evaluation-of-molecular-radiotherapy-target-expression-in-neuroblastoma-tissue
#11
Jennifer E Gains, Neil J Sebire, Veronica Moroz, Keith Wheatley, Mark N Gaze
PURPOSE: Neuroblastoma may be treated with molecular radiotherapy, (131)I meta-Iodobenzylguanidine and (177)Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy. METHODS: Tissue bank samples of formalin fixed paraffin embedded neuroblastoma tissue from patients for whom clinical outcome data were available were sectioned and stained with haematoxylin and eosin, and monoclonal antibodies directed against NAT and SSTR2...
October 17, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29043147/a-case-report-of-paraproteinemia-associated-pauci-immune-glomerulonephritis-a-new-form-of-monoclonal-gammopathy-of-renal-significance
#12
Robert Rope, Neeraja Kambham, Neiha Arora
BACKGROUND: Renal disease associated with paraproteinemias is classically predicated upon pathologic paraprotein deposition in the kidney. However, growing evidence suggests that paraproteins may be able to systemically activate complement or neutrophils to drive renal damage. This may provide an alternative pathologic mechanism for renal injury in rare cases. CASE REPORT: We report a case of a patient with crescentic pauci-immune glomerulonephritis presenting with rapidly progressive renal failure, polyarthropathy, and a purpuric rash in association with a monoclonal immunoglobulin G κ-light-chain producing multiple myeloma...
2017: Clin Nephrol Case Stud
https://www.readbyqxmd.com/read/29043014/an-open-label-study-to-evaluate-the-long-term-safety-and-efficacy-of-lanadelumab-for-prevention-of-attacks-in-hereditary-angioedema-design-of-the-help-study-extension
#13
Marc A Riedl, Jonathan A Bernstein, Timothy Craig, Aleena Banerji, Markus Magerl, Marco Cicardi, Hilary J Longhurst, Mustafa M Shennak, William H Yang, Jennifer Schranz, Jovanna Baptista, Paula J Busse
BACKGROUND: Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/29042834/improving-palivizumab-compliance-rough-a-pharmacist-managed-rsv-prevention-clinic
#14
Jennifer W Chow, Michael F Chicella, Anthony M Christensen, Carolyn S Moneymaker, John Harrington, James E Dice
OBJECTIVES: Palivizumab is a monoclonal antibody approved for the prevention of serious lower respiratory tract infections caused by respiratory syncytial virus (RSV) in high-risk pediatric patients. While palivizumab is more effective if used correctly, compliance with the monthly dosing is suboptimal. We established a pharmacist-managed RSV prevention clinic in an effort to improve compliance. The primary objective of this study was to determine the impact of a pharmacist-managed RSV prevention clinic on palivizumab compliance...
September 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29042821/practical-recommendations-for-the-use-of-therapeutic-drug-monitoring-of-biopharmaceuticals-in-inflammatory-diseases
#15
REVIEW
Erwin Dreesen, Peter Bossuyt, Denis Mulleman, Ann Gils, Dora Pascual-Salcedo
Biopharmaceuticals directed against tumor necrosis factor-alpha, integrins, interleukins, interferons and their receptors have become key agents for the management of inflammatory diseases in the fields of gastroenterology, rheumatology, dermatology and neurology. However, response to these treatments is far from optimal. Therapeutic failure has been attributed in part to inadequate serum concentrations of the drug and the formation of antidrug antibodies (ADA). Therapeutic drug monitoring (TDM) based on drug concentrations and ADA represents a pharmacologically sound tool for guiding dosage adjustments to optimize exposure...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29042750/current-perspective-on-rituximab-in-rheumatic-diseases
#16
REVIEW
Tommaso Schioppo, Francesca Ingegnoli
The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29042366/emicizumab-a-bispecific-antibody-recognizing-coagulation-factors-ix-and-x-how-does-it-actually-compare-to-factor-viii
#17
Peter J Lenting, Cécile V Denis, Olivier D Christophe
During the last decade, the development of improved and novel approaches for the treatment of hemophilia A has expanded tremendously. These approaches include factor VIII (FVIII) with extended half-life (e.g. FVIII-Fc and PEGylated FVIII), monoclonal antibodies targeting tissue factor pathway inhibitor, si-RNA to reduce antithrombin expression and the bispecific antibody ACE910/Emicizumab. Emicizumab is a bispecific antibody recognizing both the enzyme factor IXa (FIXa) and the substrate factor X (FX). By simultaneously binding enzyme and substrate, Emicizumab mimics some part of the function exerted by the original cofactor FVIII, in that it promotes co-localization of the enzyme/substrate complex...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29042196/dcir3-and-dcir4-are-co-expressed-on-inflammatory-and-patrolling-monocytes
#18
Yu Hsu, Ryo Okada, Takashi Nishimura, Norihito Kawasaki, Kazuo Yamamoto, Naoki Matsumoto
Dendritic cell inhibitory receptor 3 (DCIR3) is a member of dendritic immuno-receptor family, of which protein expression has been unknown. We established a specific monoclonal antibody against mouse DCIR3 and investigated the expression of DCIR3 on immune cells of various immune organs. We found that DCIR3 was expressed on monocytes, but not on eosinophils and neutrophils. We also found the existence of a dichotomy in the levels of the expression of DCIR3 on monocytes in bone marrow, blood and spleen. Further investigation of the expression of several cell surface markers on DCIR3(High) cells and DCIR3(Low) cells revealed that DCIR3(High) cells were Ly-6C(-) CD43(High) CD11c(+) CD80(+) NK1...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29042094/ustekinumab-to-treat-crohn-s-disease
#19
Javier P Gisbert, María Chaparro
Ustekinumab is a monoclonal antibody directed against the p40 subunit, which is part of interleukins IL-12 and IL-23. The efficacy of ustekinumab versus placebo in terms of clinical response and remission of induction has been shown in phase3 clinical trials. When used as subcutaneous maintenance therapy, the therapeutic benefit of ustekinumab over placebo has been confirmed in both clinical response and remission in patients who have responded clinically to induction therapy. In addition, ustekinumab has demonstrated an improvement in mucosal healing parameters...
October 14, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/29042015/identification-of-monoclonal-antibodies-cross-reactive-with-bottlenose-dolphin-orthologues-of-the-major-histocompatibility-complex-and-leukocyte-differentiation-molecules
#20
Mahmoud M Elnaggar, Gaber S Abdellrazeq, Stephanie K Venn-Watson, Eric D Jensen, Victoria Hulubei, Lindsay M Fry, Randy E Sacco, William C Davis
The slow progress in understanding immunotoxic effects of environmental contaminants and their influence on disease susceptibility in whales is largely due to the limited information available on the immune systems and immune function of species included in the Cetancodontamorpha clade. Studies in species in the other major clades included in the Artiodactylamorpha, Ruminantiamorpha, Suinamorpha, and Camelidamorpha have revealed the immune systems are similar, but not identical. The present study was undertaken to expand the available monoclonal antibody reagents needed to gain insight into the composition, function, and evolution of the immune system in Cetancodontamorpha, using the dolphin (Tursiops truncatus) as a model cetacean species...
October 2017: Veterinary Immunology and Immunopathology
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