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https://www.readbyqxmd.com/read/29053992/biomarker-guided-stratification-of-autoimmune-patients-for-biologic-therapy
#1
REVIEW
Sabine Ivison, Christine des Rosiers, Sylvie Lesage, John D Rioux, Megan K Levings
Autoimmunity results from an intersection of genetic and environmental factors that cause patient-specific perturbations in immune homeostasis. Defining autoimmunity-associated genetic factors has led to mechanistic insight into underlying etiologies, and the development of many biologic therapies that target the immune system. However, biomarker-informed pairing of patients with optimal biologic therapy is lacking. Here, we discuss platforms commonly used to find biomarkers that predict response to biologic therapy in autoimmunity and highlight recent biomarker discoveries...
October 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29053672/sample-extraction-and-simultaneous-chromatographic-quantitation-of-doxorubicin-and-mitomycin-c-following-drug-combination-delivery-in-nanoparticles-to-tumor-bearing-mice
#2
Rui Xue Zhang, Tian Zhang, King Chen, Ji Cheng, Paris Lai, Andrew M Rauth, K Sandy Pang, Xiao Yu Wu
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053434/alpha-gal-inactivated-heart-valve-bioprostheses-exhibit-an-anti-calcification-propensity-similar-to-knockout-tissues
#3
Filippo Naso, Ugo Stefanelli, Edward Buratto, Giovanna Lazzari, Andrea Perota, Cesare Galli, Alessandro Gandaglia
BACKGROUND: Glutaraldehyde (GLA) has been used to crosslink bioprosthetic heart valve (BHVs) tissues to enhance their stability, besides ensuring a satisfactory degree of immunological tolerance. Unfortunately, GLA fixation does not guarantee a complete tissue biocompatibility of BHVs in currently used devices. The interaction between preformed human anti-alpha-Gal antibody and alpha-Gal antigens promotes the calcification of GLA-treated alpha-Gal-positive tissue. Recently, an alarming correlation between the presence of the alpha-Gal epitope and a premature BHVs degeneracy was reported...
October 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29053220/adalimumab-and-postoperative-complications-of-elective-intestinal-resections-in-crohn-s-disease-a-propensity-score-case-matched-study
#4
Paulo Gustavo Kotze, Daniéla Oliveira Magro, Carlos Augusto Real Martinez, Barbara Saab, Mansur Paulo Saab, Lilian Vital Pinheiro, Marcia Olandoski, Takayuki Yamamoto, Claudio Saddy Rodrigues Coy
BACKGROUND: data are scarce regarding the effect of preoperative Adalimumab (ADA) in postoperative complications in Crohn's disease (CD) patients. AIM: to compare the rates of postoperative complications after intestinal resections in CD, with and without previous exposure to ADA. METHOD: case-matched retrospective observational study of patients submitted to intestinal resections for CD. The patients were allocated to 2 groups, according to their previous exposure to ADA before surgery...
October 20, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/29053152/heart-in-space-effect-of-the-extraterrestrial-environment-on-the-cardiovascular-system
#5
REVIEW
Richard L Hughson, Alexander Helm, Marco Durante
National space agencies and private corporations aim at an extended presence of humans in space in the medium to long term. Together with currently suboptimal technology, microgravity and cosmic rays raise health concerns about deep-space exploration missions. Both of these physical factors affect the cardiovascular system, whose gravity-dependence is pronounced. Heart and vascular function are, therefore, susceptible to substantial changes in weightlessness. The altered cardiovascular function in space causes physiological problems in the postflight period...
October 20, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29053051/photobiomodulation-therapy-alleviates-tissue-fibroses-associated-with-chronic-graft-versus-host-disease-two-case-reports-and-putative-anti-fibrotic-roles-of-tgf-%C3%AE
#6
Joel B Epstein, Judith E Raber-Durlacher, Marie-Charlotte Huysmans, Maria C E Schoordijk, Jerry E Cheng, Rene-Jean Bensadoun, Praveen R Arany
OBJECTIVE: Patients who receive allogeneic hematopoietic stem cell transplantation may experience oral complications due to chronic graft-versus-host disease (cGVHD). The manifestations may include progressive sclerosis-like changes that may involve various body sites, including the oropharynx. METHODS AND RESULTS: We present two cGVHD cases of oropharyngeal fibrotic changes that affected functions that were treated with photobiomodulation (PBM) therapy. These case reports suggest that PBM therapy represents an additional, innovative approach affecting discrete phases in cGVHD-associated fibrotic changes...
October 19, 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/29052818/out-of-pocket-cost-is-a-barrier-to-therapeutic-drug-monitoring-in-inflammatory-bowel-disease
#7
James P Campbell, Erin Burton, Shelly Wymer, Michael Shaw, Byron P Vaughn
BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly performed to optimize biologic therapy in inflammatory bowel disease (IBD). However, patients and physicians may be reluctant to perform TDM due to concerns related to potential out-of-pocket costs. AIMS: The aim of this study was to evaluate patient understanding and attitudes toward TDM in different clinical scenarios with and without potential out-of-pocket costs. METHODS: Adult IBD patients at a tertiary gastroenterology clinic were anonymously surveyed from March to September 2016 to assess their understanding of and willingness to undergo TDM in a variety of clinical scenarios, both with and without a potential out-of-pocket cost...
October 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29052800/dermatologist-and-patient-preferences-in-choosing-treatments-for-moderate-to-severe-psoriasis
#8
Matthew Alcusky, Seina Lee, Gordon Lau, Gretchen R Chiu, Nandini Hadker, Aparna Deshpande, Stephen Fleming, Nicola Vance, Steve Fakharzadeh
INTRODUCTION: The objective of the study was to determine the relative importance (RI) of treatment attributes psoriasis patients and physicians consider when choosing between biologic therapies based on psoriasis severity. METHODS: A discrete choice experiment (DCE) weighting preference for eight sets of hypothetical treatments for moderate or severe psoriasis was conducted. DCE hypothetical treatments were defined and varied on combinations of efficacy, safety, and dosing attributes [frequency/setting/route of administration (ROA)]...
October 20, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#9
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052423/streamlined-total-synthesis-of-trioxacarcins-and-its-application-to-the-design-synthesis-and-biological-evaluation-of-analogues-thereof-discovery-of-simpler-designed-and-potent-trioxacarcin-analogues
#10
K C Nicolaou, Pengxi Chen, Shugao Zhu, Quan Cai, Rohan D Erande, Ruofan Li, Hongbao Sun, Kiran Kumar Pulukuri, Stephan Rigol, Monette Aujay, Joseph Sandoval, Julia Gavrilyuk
A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described...
October 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29052220/efficacy-from-strange-sources
#11
Lawrence Lesko
Reverse translation (RT) refers to perceptions and observations of clinical outcomes, both beneficial and harmful, that can lead to a hypothesis intended to identify a new use of a drug that is different than the original use. I provide a panoramic view of successes in RT from the historic discovery of penicillin to the contemporary development of CAR T therapies. I delineate the core principles of RT that shift discovery from serendipity to a systematic strategy based on target identification based on causal biology, pharmacodynamic biomarkers that recapitulates disease pathophysiology, confirmation of target engagement by clinical proof of concept studies, and optimal selection of dose and interval...
October 20, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29052134/kaposi-s-sarcoma-associated-herpesvirus-epidemiology-and-molecular-biology
#12
Shasha Li, Lei Bai, Jiazhen Dong, Rui Sun, Ke Lan
Kaposi's sarcoma-associated herpesvirus (KSHV), also known as Human herpesvirus 8 (HHV-8), is a member of the lymphotropic gammaherpesvirus subfamily and a human oncogenic virus. Since its discovery in AIDS-associated KS tissues by Drs. Yuan Chang and Patrick Moore, much progress has been made in the past two decades. There are four types of KS including classic KS, endemic KS, immunosuppressive therapy-related KS, and AIDS-associated KS. In addition to KS, KSHV is also involved in the development of primary effusion lymphoma (PEL) and certain types of multicentric Castleman's disease...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29052093/emerging-small-molecule-approaches-to-enhance-the-antimyeloma-benefit-of-proteasome-inhibitors
#13
James J Driscoll, Magen Brailey
Multiple myeloma (MM) is a clonal plasma cell malignancy which, despite recent treatment advances, remains incurable in the vast majority of the over 118,000 patients in the USA afflicted with this disease. Treatment of MM has dramatically improved in the past decade with the introduction of new drugs into therapeutic strategies in both the frontline and relapse settings that has led to a significant improvement in the median overall survival (OS). These drugs have been incorporated into clinical guidelines and transformed the treatment approach to MM...
October 19, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29051788/emerging-oral-targeted-therapies-in-inflammatory-bowel-diseases-opportunities-and-challenges
#14
REVIEW
Marcel Vetter, Markus F Neurath
To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn's disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins...
October 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29051036/characterization-of-disease-burden-comorbidities-and-treatment-use-in-a-large-us-based-cohort-results-from-the-corrona-psoriasis-registry
#15
Bruce Strober, Chitra Karki, Marc Mason, Ning Guo, Stacey H Holmgren, Jeffrey D Greenberg, Mark Lebwohl
BACKGROUND: Psoriasis is an immunodysregulatory inflammatory disease associated with comorbidities impacting quality of life. With the advent of new treatments, there is growing need to assess the long term safety and efficacy of treatments in a real-world setting. OBJECTIVES: The objective of the Corrona Psoriasis Registry is to study the comparative safety and efficacy of FDA approved biologic treatments. METHODS: A cross-sectional study of patients enrolled in the registry, who initiated/switched to a systemic therapy at enrollment/previous 12 months...
October 16, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29050915/decellularized-matrix-of-adipose-derived-mesenchymal-stromal-cells-enhanced-retinal-progenitor-cell-proliferation-via-the-akt-erk-pathway-and-neuronal-differentiation
#16
Jing Ji, Dandan Zhang, Wei Wei, Bingqiao Shen, Yi Zhang, Yuyao Wang, Zhimin Tang, Ni Ni, Hao Sun, Jiaqiang Liu, Xianqun Fan, Ping Gu
BACKGROUND AIMS: Retinal progenitor cells (RPCs) are a promising cell therapy treatment for retinal degenerative diseases. However, problems with limited proliferation ability and differentiation preference toward glia rather than neurons restrict the clinical application of these RPCs. The extracellular matrix (ECM) has been recognized to provide an appropriate microenvironment to support stem cell adhesion and direct cell behaviors, such as self-renewal and differentiation. METHODS: In this study, decellularized matrix of adipose-derived mesenchymal stromal cells (DMA) was manufactured using a chemical agent method (0...
October 16, 2017: Cytotherapy
https://www.readbyqxmd.com/read/29050839/recommendations-by-the-spanish-society-of-rheumatology-on-the-use-of-biological-therapies-in-axial-spondyloarthritis
#17
Jordi Gratacós, Petra Díaz Del Campo Fontecha, Cristina Fernández-Carballido, Xavier Juanola Roura, Luis Francisco Linares Ferrando, Eugenio de Miguel Mendieta, Santiago Muñoz Fernández, Jose Luis Rosales-Alexander, Pedro Zarco Montejo, Mercedes Guerra Rodríguez, Victoria Navarro Compán
OBJECTIVE: Recent data published on biological therapy in axial spondyloarthritis (axSpA) since the last publication of the recommendations of the Spanish Society of Rheumatology (SER) has led to the generation of a review of these recommendations based on the best possible evidence. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with axSpA. METHODS: Recommendations were drawn up following a nominal group methodology and based on systematic reviews...
October 16, 2017: Reumatología Clinica
https://www.readbyqxmd.com/read/29050787/transplantation-routes-affect-the-efficacy-of-human-umbilical-cord-mesenchymal-stem-cells-in-a-rat-gdm-model
#18
Dan Wu, Shan Zou, Haibin Chen, Xiaoyan Li, Yetao Xu, Qing Zuo, Yi Pan, Shi-Wen Jiang, Huan Huang, Lizhou Sun
Gestational diabetes mellitus (GDM) is harmful to both the mother and fetus. Although transplantation of human umbilical cord mesenchymal stem cells (HUMSCs) could be a useful therapy for GDM, the influences of different transplantation routes on the therapeutic effects remain unclear. In this study, we isolated and cultured the HUMSCs for transplantation, and the biological activity of HUMSCs was verified by flow cytometric analysis (the positive markers, CD44, CD73, CD105 and CD90, the negative markers, CD45, CD34, CD19, HLA-DR, and CD11b) and potency of osteogenic, adipogenic and chondrogenic differentiation...
October 16, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29050694/the-biology-of-philadelphia-chromosome-like-all
#19
REVIEW
Kathryn G Roberts
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently described subtype of B-cell precursor ALL with a gene expression profile similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to over 25% of young adults with ALL. It occurs more frequently in males and is associated with adverse clinical features including elevated minimal residual disease levels and poor survival in both children and adults...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050380/inflammasomes-in-neurological-diseases-emerging-pathogenic-and-therapeutic-concepts
#20
Manmeet K Mamik, Christopher Power
Inflammasome activation in the central nervous system occurs in both health and disease. Inflammasomes are cytosolic protein complexes that sense specific infectious or host stimuli and initiate inflammatory responses through caspase activation. Assembly of inflammasomes results in caspase-1-mediated proteolytic cleavage and release of the pro-inflammatory cytokines, interleukin-1β and interleukin-18, with initiation of pyroptosis, an inflammatory programmed cell death. Recent developments in the inflammasome field have uncovered novel molecular mechanisms that contribute to a broad range of neurological disorders including those associated with specific mutations in inflammasome genes as well as diseases modulated by inflammasome activation...
September 1, 2017: Brain: a Journal of Neurology
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