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Biologics: Targets & Therapy

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https://www.readbyqxmd.com/read/28442889/cul4a-promotes-cell-invasion-in-gastric-cancer-by-activating-the-nf-%C3%AE%C2%BAb-signaling-pathway
#1
Yu Gong, Xiao-Jun Xiang, Miao Feng, Jun Chen, Zi-Ling Fang, Jian-Ping Xiong
Cullin 4A (CUL4A) overexpression has been reported to be involved in the carcinogenesis and progression of many malignant tumors. However, the role of CUL4A in the progression of gastric cancer (GC) remains unclear. In this study, we explored whether and how CUL4A regulates proinflammatory signaling to promote GC cell invasion. Our results showed that knockdown of CUL4A inhibited GC cell migration and invasion induced by lipopolysaccharide (LPS) stimulation. We also found that both CUL4A and nuclear factor-kappa B (NF-κB) protein expressions were enhanced by LPS stimulation in HGC27 GC cell lines...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28442888/new-developments-in-the-treatment-of-multiple-myeloma-clinical-utility-of-daratumumab
#2
REVIEW
Cian McEllistrim, Janusz Krawczyk, Michael E O'Dwyer
Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28331286/neutralizing-activities-against-seasonal-influenza-viruses-in-human-intravenous-immunoglobulin
#3
Hiroyuki Onodera, Takeru Urayama, Kazue Hirota, Kazuhiro Maeda, Ritsuko Kubota-Koketsu, Kazuo Takahashi, Katsuro Hagiwara, Yoshinobu Okuno, Kazuyoshi Ikuta, Mikihiro Yunoki
Influenza viruses A/H1N1, A/H3N2, and B are known seasonal viruses that undergo annual mutation. Intravenous immunoglobulin (IVIG) contains anti-seasonal influenza virus globulins. Although the virus-neutralizing (VN) titer is an indicator of protective antibodies, changes in this titer over extended time periods have yet to be examined. In this study, variations in hemagglutination inhibition (HI) and VN titers against seasonal influenza viruses in IVIG lots over extended time periods were examined. In addition, the importance of monitoring the reactivity of IVIG against seasonal influenza viruses with varying antigenicity was evaluated...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28280299/a-practical-guide-about-biosimilar-data-for-health-care-providers-treating-inflammatory-diseases
#4
REVIEW
Joseph Markenson, Daniel F Alvarez, Ira Jacobs, Carol Kirchhoff
To make informed decisions about the safety, efficacy, and clinical utility of a biosimilar, health care providers should understand the types and be able to analyze data generated from a biosimilar development program. This article reviews the biosimilar guidelines, the biosimilar development process to provide education and context about biosimilarity, and uses examples from infliximab biosimilars to review the terminology and potential types of analyses that may be used to compare potential biosimilars to the originator biologic...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28255229/biosimilars-and-the-extrapolation-of-indications-for-inflammatory-conditions
#5
REVIEW
John Rp Tesser, Daniel E Furst, Ira Jacobs
Extrapolation is the approval of a biosimilar for use in an indication held by the originator biologic not directly studied in a comparative clinical trial with the biosimilar. Extrapolation is a scientific rationale that bridges all the data collected (ie, totality of the evidence) from one indication for the biosimilar product to all the indications originally approved for the originator. Regulatory approval and marketing authorization of biosimilars in inflammatory indications are made on a case-by-case and agency-by-agency basis after evaluating the totality of evidence from the entire development program...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28008224/centrosome-a-promising-anti-cancer-target
#6
REVIEW
Yainyrette Rivera-Rivera, Harold I Saavedra
The centrosome, an organelle discovered >100 years ago, is the main microtubule-organizing center in mammalian organisms. The centrosome is composed of a pair of centrioles surrounded by the pericentriolar material (PMC) and plays a major role in the regulation of cell cycle transitions (G1-S, G2-M, and metaphase-anaphase), ensuring the normality of cell division. Hundreds of proteins found in the centrosome exert a variety of roles, including microtubule dynamics, nucleation, and kinetochore-microtubule attachments that allow correct chromosome alignment and segregation...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27942203/pharmacoutilization-of-epoetins-in-na%C3%A3-ve-patients-with-hematological-malignancies-in-an-unselected-italian-population-under-clinical-practice-setting-a-comparative-analysis-between-originator-and-biosimilars
#7
Valentina Perrone, Stefania Saragoni, Stefano Buda, Alessandro Broccoli, Luca Degli Esposti
AIM: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in naïve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. METHODS: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27853353/update-on-sepsis-associated-acute-kidney-injury-emerging-targeted-therapies
#8
REVIEW
James F Doyle, Lui G Forni
Sepsis-associated acute kidney injury (SA-AKI) is an independent predictor of increased mortality and morbidity. It is essential that further advances in the treatment of sepsis should prioritize targeted therapies in SA-AKI in order to improve these bleak outcomes. As yet, a unique therapy that effectively reduces the impact of acute kidney injury has not been demonstrated. However, the emergence of novel targeted therapies, perhaps in combination, has the possibility of significantly reducing the long-term sequelae of an episode of SA-AKI...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27703327/eag1-channels-as-potential-early-stage-biomarkers-of-hepatocellular-carcinoma
#9
REVIEW
María de Guadalupe Chávez-López, Violeta Zúñiga-García, Julio Isael Pérez-Carreón, Arturo Avalos-Fuentes, Yesenia Escobar, Javier Camacho
Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide. HCC is usually asymptomatic at potential curative stages, and it has very poor prognosis if detected later. Thus, the identification of early biomarkers and novel therapies is essential to improve HCC patient survival. Ion channels have been proposed as potential tumor markers and therapeutic targets for several cancers including HCC. Especially, the ether à-go-go-1 (Eag1) voltage-gated potassium channel has been suggested as an early marker for HCC...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27672308/therapeutic-efficacy-of-monthly-subcutaneous-injection-of-daclizumab-in-relapsing-multiple-sclerosis
#10
REVIEW
Stanley Cohan
Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit-risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56(bright) natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27536062/new-targeted-treatments-for-non-small-cell-lung-cancer-role-of-nivolumab
#11
REVIEW
Giulia Zago, Mirte Muller, Michel van den Heuvel, Paul Baas
Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27462140/neutralizing-activities-of-human-immunoglobulin-derived-from-donors-in-japan-against-mosquito-borne-flaviviruses-japanese-encephalitis-virus-west-nile-virus-and-dengue-virus
#12
Mikihiro Yunoki, Takeshi Kurosu, Ritsuko Kubota Koketsu, Kazuo Takahashi, Yoshinobu Okuno, Kazuyoshi Ikuta
Japanese encephalitis virus (JEV), West Nile virus (WNV), and dengue virus (DenV) are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27462139/guanine-nucleotide-exchange-factor-h1-can-be-a-new-biomarker-of-melanoma
#13
Jie Shi, Bingyu Guo, Yu Zhang, Qiang Hui, Peng Chang, Kai Tao
Guanine nucleotide exchange factor H1 (GEF-H1), which couples microtubule dynamics to RhoA activation, is a microtubule-regulated exchange factor. Studies have shown that GEF-H1 can be involved in various cancer pathways; however, the clinical significance of GEF-H1 expression and functions in melanoma has not been established. In this study, we investigated the relationship between clinical outcomes and GEF-H1 functions in melanoma. A total of 60 cases of different grades of melanoma samples were used to detect the expression of GEF-H1...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27307702/effects-of-fucoidan-from-fucus-vesiculosus-in-reducing-symptoms-of-osteoarthritis-a-randomized-placebo-controlled-trial
#14
Stephen P Myers, Ann M Mulder, Don G Baker, Shelley R Robinson, Margaret I Rolfe, Lyndon Brooks, J Helen Fitton
PURPOSE: Preliminary investigation of a fucoidan with demonstrated reduction in the symptoms of osteoarthritis (OA) of the hip and knee. PATIENTS AND METHODS: A double-blind randomized controlled trial was carried out to determine the safety and efficacy of a 300 mg dose of a Fucus vesiculosus extract (85% fucoidan) over a 12-week period in a population (n=122) with mild-to-moderate OA of the hip and knee as measured by the validated instrument "Comprehensive Osteoarthritis Test...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27110096/efficacy-of-anti-il-1-treatment-in-familial-mediterranean-fever-a-systematic-review-of-the-literature
#15
Jeroen Ch van der Hilst, Michel Moutschen, Peter E Messiaen, Bernard R Lauwerys, Steven Vanderschueren
INTRODUCTION: In 5%-10% of patients with familial Mediterranean fever (FMF), colchicine is not effective in preventing inflammatory attacks. Another 5%-10% of patients are intolerant to effective doses of colchicine and experience serious side effects. Treatment with anti-interleukin-1 (IL-1) drugs may be an alternative for these patients, although it is not reimbursed for this indication in many countries. METHODS: We systematically searched PubMed, Web of Science, and Scopus for reports of anti-IL-1 treatment in FMF patients...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27099470/cost-effectiveness-of-routine-measuring-of-serum-drug-concentrations-and-anti-drug-antibodies-in-treatment-of-rheumatoid-arthritis-patients-with-tnf-%C3%AE-blockers
#16
Juha Laine, T Sakari Jokiranta, Kari K Eklund, Merja Väkeväinen, Kari Puolakka
Monitoring of anti-drug antibodies (ADAbs) or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF)-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL) and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27069354/tocilizumab-in-refractory-rheumatoid-arthritis-long-term-efficacy-safety-and-tolerability-beyond-2-years
#17
Ziad Farah, Sabreen Ali, Fiona Price-Kuehne, Charles G Mackworth-Young
OBJECTIVES: To evaluate the long-term efficacy and safety of tocilizumab (TCZ) in clinical patients with rheumatoid arthritis (RA) refractory to synthetic disease-modifying antirheumatic drugs, anti-tumor necrosis factor agents, and B-cell depletion therapy with rituximab (RTX). METHODS: We conducted a single-center retrospective study of 22 patients with RA treated with TCZ. We collected data including demographics and medication histories. We recorded clinical parameters including tender joint counts and swollen joint counts, and laboratory parameters including inflammatory makers and lipid profiles over regular intervals of TCZ treatment...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27041992/correlations-between-immunogenicity-drug-levels-and-disease-activity-in-an-italian-cohort-of-rheumatoid-arthritis-patients-treated-with-tocilizumab
#18
Maurizio Benucci, Francesca Meacci, Valentina Grossi, Maria Infantino, Mariangela Manfredi, Emanuele Bellio, Valerio Bellio, Francesca Li Gobbi, Laura Bazzichi, Paolo Moscato, Dario Caputo, Gianantonio Saviola, Rossella Talotta, Piercarlo Sarzi-Puttini, Fabiola Atzeni
The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated patients with rheumatoid arthritis (16 males and 110 females; mean age 59±12 years, range 26-83; mean disease duration 11±5 years) with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27022240/selective-biologics-for-ulcerative-colitis-and-crohn-s-disease-clinical-utility-of-vedolizumab
#19
REVIEW
Jill Mv Petkau, Bertus Eksteen
Inflammatory bowel disease (IBD) encompasses a cluster of different disease phenotypes which are broadly classified into ulcerative colitis and Crohn's disease. Disease pathogenesis is driven by abnormal host immune responses to their resident gut microbiome in genetically susceptible individuals. Clinical disease features and outcomes are heterogenous and not unexpected as over 163 genetic loci are associated with disease susceptibility, and there are great variability in environmental exposures. Despite this variability, there has been relatively few efficacious therapies for particularly moderate-to-severe IBD...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27013862/update-on-the-management-of-philadelphia-chromosome-positive-chronic-myelogenous-leukemia-role-of-nilotinib
#20
REVIEW
Josephine Emole, Taiwo Talabi, Javier Pinilla-Ibarz
Chronic myelogenous leukemia (CML) is a pluripotent stem cell disease characterized by the presence of the Philadelphia chromosome and the bcr-abl gene. The discovery of tyrosine kinase inhibitors (TKIs) revolutionized therapy for CML, such that durable response, increased overall survival, and increased progression-free survival of patients in chronic phase CML is now possible. Due to resistance and intolerance to imatinib, there was need for development of second- and third-generation TKIs for the treatment of CML...
2016: Biologics: Targets & Therapy
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