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https://www.readbyqxmd.com/read/28528528/ustekinumab-a-review-in-moderate-to-severe-crohn-s-disease
#1
Yvette N Lamb, Sean T Duggan
Ustekinumab (Stelara(®)) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists...
May 20, 2017: Drugs
https://www.readbyqxmd.com/read/28528521/myeloid-populations-in-systemic-autoimmune-diseases
#2
REVIEW
María Morell, Nieves Varela, Concepción Marañón
Systemic autoimmune diseases (SADs) encompass a wide spectrum of clinical signs as a reflection of their complex physiopathology. A variety of mechanisms related with the innate immune system are in the origin of the loss of self-tolerance in these diseases, and for most of them, the myeloid leukocytes are key actors. Monocytes, macrophages, dendritic cells, and neutrophils are first-line immune effectors located in the interface between innate and adaptive immunity. They are crucial in the organization of the local and systemic responses to damage-associated molecular patterns (DAMPs) and determine the intensity, orientation, and duration of the local immune response through the expression of chemokines, costimulatory or protolerogenic factors...
May 20, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#3
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28528507/mertk-does-not-mediate-phagocytosis-of-staphylococcus-aureus-but-attenuates-inflammation-induced-by-staphylococcal-lipoteichoic-acid-through-blocking-nf-%C3%AE%C2%BAb-activation
#4
Bing Zhang, Huimei Wu, Lei Fang, Peishan Ding, Ke Xu, Qingbin Yang, Rongyu Liu
Mer receptor tyrosine kinase (MerTK) expressed in macrophages is essential for phagocytosis of apoptotic cells. Here, we investigate whether MerTK is involved in the phagocytosis of Staphylococcus aureus (S. aureus) and regulation of staphylococcal lipoteichoic acid (LTA)-induced inflammatory response in macrophages. We found that stimulating RAW264.7 macrophages with S. aureus activated multiple signaling pathways including toll-like receptor 2 (TLR2), scavenger receptor A (SR-A), and MerTK. Meanwhile, S. aureus stimulation also induced activation of proteins focal adhesion kinase (FAK) and Rac1, which are related to phagocytosis...
May 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28528167/cxcl1-inhibition-regulates-uvb-induced-skin-inflammation-and-tumorigenesis-in-xpa-deficient-mice
#5
Makoto Kunisada, Chieko Hosaka, Chihiro Takemori, Eiji Nakano, Chikako Nishigori
Xeroderma pigmentosum complementation group A (XP-A) is a hereditary disease characterized by early onset of skin cancers and freckles-like pigmented maculae in the sun-exposed sites. Although etiology of predisposition to UV-induced skin tumors in XP-A is well investigated as a repair deficiency in UV-induced DNA damage, the mechanism of exaggerated sunburn in patients with XP-A and whether UV-induced inflammation relates to skin tumor-prone phenotype remains to be elucidated. Using gene profiling of XP-A model mice, Xpa-deficient mice, we found that expression of CXCL1 in the skin and blood levels of in Xpa-deficient mice increased significantly after UVB exposure at an even a limited area in comparison to those of wild-type mice...
May 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28528009/identification-of-novel-haemophilus-parasuis-serovar-5-vaccine-candidates-using-an-immunoproteomic-approach
#6
Gang Li, Fang Xie, Jianjun Li, Jiao Liu, Dapeng Li, Yanhe Zhang, Paul R Langford, Yanwen Li, Siguo Liu, Chunlai Wang
Haemophilus parasuis is the aetiological agent of Glässer's disease, which is responsible for cases of fibrinous polyserositis, polyarthritis and meningitis. No vaccine is known that provides cross-protection against all serovars. The identification of novel immunoprotective antigens would undoubtedly contribute to the development of efficient subunit vaccines. In the present study, an immunoproteomic approach was used to analyze secreted proteins of H. parasuis and six proteins with high immunogenicity were identified...
May 17, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28527850/complement-activation-by-pulp-capping-materials-plays-a-significant-role-in-both-inflammatory-and-pulp-stem-cells-recruitment
#7
Thomas Giraud, Pierre Rufas, Fanny Chmilewsky, Charlotte Rombouts, Jacques Dejou, Charlotte Jeanneau, Imad About
INTRODUCTION: The role of complement, especially through the C5a fragment, is well-known for the initiation of inflammation. Its involvement in regeneration has been shown more recently by the recruitment of mesenchymal stem cells. C5a can be produced locally by the pulp fibroblasts in response to injury or infection. This work aims to investigate the effect of different pulp capping biomaterials on complement activation and its possible influence on inflammatory and pulp stem cell recruitment...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28527839/modulation-of-matrix-metalloproteinase-14-tissue-inhibitor-of-metalloproteinase-3-tissue-inhibitor-of-metalloproteinase-4-and-inducible-nitric-oxide-synthase-in-the-development-of-periapical-lesions
#8
Lorena Teodoro de Castro Cassanta, Virmondes Rodrigues, Jose Roberto Violatti-Filho, Benedito Alves Teixeira Neto, Vinícius Marques Tavares, Eduarda Castelo Branco Araujo Bernal, Danila Malheiros Souza, Marcelo Sivieri Araujo, Sanivia Aparecida de Lima Pereira, Denise Bertulucci Rocha Rodrigues
INTRODUCTION: Periapical cysts and granulomas are chronic lesions caused by an inflammatory immune response against microbial challenge in the root canal. Different cell types, cytokines, and molecules have been associated with periapical lesion formation and expansion. Therefore, because of the chronic inflammatory state of these lesions, the aim of this study was to evaluate the in situ expression of matrix metalloproteinase (MMP)-14 and -19, tissue inhibitor of metalloproteinase (TIMP)-3 and -4, CD68, and inducible nitric oxide synthase (iNOS) in periapical cysts and granulomas...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28527686/local-innate-responses-and-protective-immunity-after-intradermal-immunization-with-bovine-viral-diarrhea-virus-e2-protein-formulated-with-a-combination-adjuvant-in-cattle
#9
Sams M A Sadat, Marlene Snider, Ravendra Garg, Robert Brownlie, Sylvia van Drunen Littel-van den Hurk
Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens in cattle. Recently, we developed a novel adjuvant platform (TriAdj) that includes a toll-like receptor 3 agonist, poly (I:C); an innate defense regulatory peptide; and water-soluble polymer, poly[di(sodiumcarboxylatoethylphenoxy)]-phosphazene (PCEP). To develop a needle-free intradermal (ID) subunit vaccine, the BVDV type-2 E2 protein was formulated with TriAdj, and immune protection was evaluated in calves against a BVDV-2 strain. Intradermal delivery of E2/TriAdj elicited robust virus neutralizing antibodies and cell-mediated immune responses including CD4(+) and CD8(+) T-cell responses...
May 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28527133/a-phase-ii-study-of-antibody-drug-conjugate-tak-264-mln0264-in-previously-treated-patients-with-advanced-or-metastatic-pancreatic-adenocarcinoma-expressing-guanylyl-cyclase-c
#10
Khaldoun Almhanna, David Wright, Teresa Macarulla Mercade, Jean-Luc Van Laethem, Antonio Cubillo Gracian, Carmen Guillen-Ponce, Jason Faris, Carolina Muriel Lopez, Richard A Hubner, Johanna Bendell, Alain Bols, Jaime Feliu, Naureen Starling, Peter Enzinger, Devalingham Mahalingham, Wells Messersmith, Huyuan Yang, Adedigbo Fasanmade, Hadi Danaee, Thea Kalebic
Background This phase II open-label, multicenter study evaluated the efficacy, safety, and tolerability of TAK-264 in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC). Methods Patients with advanced or metastatic pancreatic adenocarcinoma expressing GCC (H-score ≥ 10) received TAK-264 1.8 mg/kg on day 1 of a 21-day cycle as a 30-min intravenous infusion for up to 1 year or until disease progression or unacceptable toxicity. The primary objective was overall response rate (ORR [complete response + partial response (PR)])...
May 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28527063/the-role-of-anti-cgrp-antibodies-in-the-pathophysiology-of-primary-headaches
#11
Piero Barbanti, Cinzia Aurilia, Luisa Fofi, Gabriella Egeo, Patrizia Ferroni
Calcitonin gene-related peptide (CGRP), a potent vasodilator and pain-signaling neuropeptide, is a validated therapeutic target for migraine and cluster headache. Four anti-CGRP monoclonal antibodies (mAbs) have been developed, representing the first specific, mechanism-based, migraine prophylactic treatment. CGRP mAbs demonstrated good efficacy coupled to excellent tolerability and safety in 5 phase II clinical trials. Notably, CGRP mAbs induced complete migraine remission in a patients' subset. To date, more than 20 phase III trials using CGRP mAbs for of episodic and chronic migraine and cluster headache prevention are ongoing...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28526733/discovery-and-optimization-of-hkt288-a-cadherin-6-targeting-adc-for-the-treatment-of-ovarian-and-renal-cancer
#12
Carl U Bialucha, Scott D Collins, Xiao Li, Parmita Saxena, Xiamei Zhang, Clemens Dürr, Bruno LaFont, Pierric Prieur, Yeonju Shim, Rebecca Mosher, David Lee, Lance Ostrom, Tiancen Hu, Sanela Bilic, Ivana Liric Rajlic, Vladimir Capka, Wei Jiang, Joel P Wagner, GiNell Elliott, Artur Veloso, Jessica C Piel, Meghan M Flaherty, Keith G Mansfield, Emily K Meseck, Tina Rubic-Schneider, Anne Serdakowski London, William R Tschantz, Markus Kurz, Duc Nguyen, Aaron Bourret, Matthew J Meyer, Jason E Faris, Mary J Janatpour, Vivien W Chan, Nicholas C Yoder, Kalli C Catcott, Molly A McShea, Xiuxia Sun, Hui Gao, Juliet Williams, Francesco Hofmann, Jeffrey A Engelman, Seth A Ettenberg, William R Sellers, Emma Lees
Despite an improving therapeutic landscape, significant challenges remain in treating the majority of advanced ovarian and renal cancer patients. We identified the cell-cell adhesion molecule cadherin-6 (CDH6) as a lineage gene having significant differential expression in ovarian and kidney cancer. HKT288 is an optimized CDH6-targeting DM4-based antibody drug conjugate (ADC) developed for the treatment of these diseases. Our study provides mechanistic evidence supporting the importance of linker choice for optimal anti-tumor activity and highlights CDH6 as a novel antigen for biotherapeutic development...
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28526726/are-phloem-sieve-tubes-leaky-conduits-supported-by-numerous-aquaporins
#13
Ryan C Stanfield, Uwe G Hacke, Joan Laur
PREMISE OF THE STUDY: Aquaporin membrane water channels have been previously identified in the phloem of angiosperms, but currently their cellular characterization is lacking, especially in tree species. Pinpointing the cellular location will help generate new hypotheses of how membrane water exchange facilitates sugar transport in plants. METHODS: We studied histological sections of balsam poplar (Populus balsamifera L.) in leaf, petiole, and stem organs. Immuno-labeling techniques were used to characterize the distribution of PIP1 and PIP2 subfamilies of aquaporins along the phloem pathway...
May 19, 2017: American Journal of Botany
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#14
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526278/biotherapeutics-in-chronic-rhinosinusitis-with-and-without-nasal-polyps
#15
Claus Bachert, Philippe Gevaert, Peter Hellings
In western countries, 85% of chronic rhinosinusitis with nasal polyp disease reveals a type 2 inflammatory pattern with expression of IL-4, -5, and -13 as well as increased concentrations of IgE, whereas chronic rhinosinusitis without nasal polyps merely expresses these biomarkers. The degree of type 2 inflammation furthermore is associated with disease severity, asthma comorbidity, and recurrence of disease after surgery. Therefore, these biomarkers also form the targets for innovative therapeutic approaches such as monoclonal antibodies directed against IgE, IL-5, and IL-4 receptor alpha, blocking the activity of IL-4 and -13...
May 16, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28526017/the-effect-of-hypoxia-on-the-lipidome-of-recombinant-pichia-pastoris
#16
Núria Adelantado, Pablo Tarazona, Karlheinz Grillitsch, Xavier García-Ortega, Sergi Monforte, Francisco Valero, Ivo Feussner, Günther Daum, Pau Ferrer
BACKGROUND: Cultivation of recombinant Pichia pastoris (Komagataella sp.) under hypoxic conditions has a strong positive effect on specific productivity when the glycolytic GAP promoter is used for recombinant protein expression, mainly due to upregulation of glycolytic conditions. In addition, transcriptomic analyses of hypoxic P. pastoris pointed out important regulation of lipid metabolism and unfolded protein response (UPR). Notably, UPR that plays a role in the regulation of lipid metabolism, amino acid metabolism and protein secretion, was found to be upregulated under hypoxia...
May 19, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#17
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525878/vaccine-development-for-respiratory-syncytial-virus
#18
REVIEW
Barney S Graham
Respiratory syncytial virus (RSV) is an important and ubiquitous respiratory pathogen for which no vaccine is available notwithstanding more than 50 years of effort. It causes the most severe disease at the extremes of age and in settings of immunodeficiency. Although RSV is susceptible to neutralizing antibody, it has evolved multiple mechanisms of immune evasion allowing it to repeatedly infect people despite relatively little genetic diversity. Recent breakthroughs in determining the structure and antigenic content of the fusion (F) glycoprotein in its metastable untriggered prefusion form (pre-F) and the stable rearranged postfusion form (post-F) have yielded vaccine strategies that can induce potent neutralizing antibody responses and effectively boost pre-existing neutralizing activity...
May 16, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28525848/an-amplified-comparative-fluorescence-resonance-energy-transfer-immunosensing-of-ca125-tumor-marker-and-ovarian-cancer-cells-using-green-and-economic-carbon-dots-for-bio-applications-in-labeling-imaging-and-sensing
#19
Somayeh Hamd-Ghadareh, Abdollah Salimi, Fardin Fathi, Saman Bahrami
CA125, is a marker in the clinical diagnosis of several cancers and currently is the best serum-based tumor marker for ovarian cancer. Here, we developed an ultrasensitive antibody-ssDNA aptamer sandwich-type fluorescence immunosensor for CA125 detection. Based on a novel signal amplification strategy the carbon dots (CDs) functionalized with aptamer (CD-aptamer) used as detection probe and PAMAM-Dendrimers/AuNPs was used for covalent attachment of CA125-antibody and completing the sandwich assay method. By measuring of fluorescence resonance energy transfer (FRET) signals between CDs and AuNPs as nanoquenchers, the fluorescence signal quenched during sandwich complex formed between anti-CA125, CA125 and CDs-Aptamer and decreasing of fluorescence response signal is related to CA125 concentrations...
May 4, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#20
Xuelian Zhao, Katie A Howell, Shihua He, Jennifer M Brannan, Anna Z Wec, Edgar Davidson, Hannah L Turner, Chi-I Chiang, Lin Lei, J Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N Turonis, Ana I Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S Spence, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, Kartik Chandran, John M Dye, Xiangguo Qiu, Yuxing Li, M Javad Aman
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets...
May 18, 2017: Cell
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