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https://www.readbyqxmd.com/read/28737744/delivering-advanced-therapies-the-big-pharma-approach
#1
REVIEW
J Tarnowski, D Krishna, L Jespers, A Ketkar, R Haddock, J Imrie, S Kili
After two decades of focused development and some recent clinical successes, cell and gene therapy (CGT) is emerging as a promising approach to personalized medicines. Genetically engineered cells as a medical modality are poised to stand alongside or in combination with small molecule and biopharmaceutical approaches to bring new therapies to patients globally. Big pharma can play a vital role in industrializing CGT by focusing on diseases with high un-met medical need and compelling genetic evidence. Pharma should invest in manufacturing and supply chain solutions that deliver reproducible, high quality therapies at a commercially viable cost...
July 24, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28737465/the-effect-of-ozone-gas-sterilization-on-the-properties-and-cell-compatibility-of-electrospun-polycaprolactone-scaffolds
#2
Carolina Fracalossi Rediguieri, Paul A De Bank, Maria Helena Ambrosio Zanin, Patrícia Leo, Natalia Neto Pereira Cerize, Adriano Marim de Oliveira, Terezinha de Jesus Andreoli Pinto
The growing area of tissue engineering has the potential to alleviate the shortage of tissues and organs for transplantation, and electrospun biomaterial scaffolds are extremely promising devices for translating engineered tissues into a clinical setting. However, to be utilized in this capacity, these medical devices need to be sterile. Traditional methods of sterilization are not always suitable for biomaterials, especially as many commonly used biomedical polymers are sensitive to chemical-, thermal- or radiation-induced damage...
July 24, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28736687/tissue-engineered-tendon-for-enthesis-regeneration-in-a-rat-rotator-cuff-model
#3
Michael J Smietana, Pablo Moncada-Larrotiz, Ellen M Arruda, Asheesh Bedi, Lisa M Larkin
Healing of rotator cuff (RC) injuries with current suture or augmented scaffold techniques fails to regenerate the enthesis and instead forms a weaker fibrovascular scar that is prone to subsequent failure. Regeneration of the enthesis is the key to improving clinical outcomes for RC injuries. We hypothesized that the utilization of our tissue-engineered tendon to repair either an acute or a chronic full-thickness supraspinatus tear would regenerate a functional enthesis and return the biomechanics of the tendon back to that found in native tissue...
2017: BioResearch Open Access
https://www.readbyqxmd.com/read/28736613/cd200-modulates-macrophage-cytokine-secretion-and-phagocytosis-in-response-to-poly-lactic-co-glycolic-acid-microparticles-and-films
#4
E Y Chen, S Chu, L Gov, Y K Kim, M B Lodoen, A J Tenner, W F Liu
Biocompatibility is a major concern for developing biomaterials used in medical devices, tissue engineering and drug delivery. Poly(lactic-co-glycolic acid) (PLGA) is one of the most widely used biodegradable materials, yet still triggers a significant foreign body response that impairs healing. Immune cells including macrophages respond to the implanted biomaterial and mediate the host response, which can eventually lead to device failure. Previously in our laboratory, we found that CD200, an immunomodulatory protein, suppressed macrophage inflammatory activation in vitro and reduced local immune cell infiltration around a biomaterial implant...
February 28, 2017: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28735373/systematic-heuristic-evaluation-of-computerized-consultation-order-templates-clinicians-and-human-factors-engineers-perspectives
#5
April Savoy, Himalaya Patel, Mindy E Flanagan, Michael Weiner, Alissa L Russ
We assessed the usability of consultation order templates and identified problems to prioritize in design efforts for improving referral communication. With a sample of 26 consultation order templates, three evaluators performed a usability heuristic evaluation. The evaluation used 14 domain-independent heuristics and the following three supplemental references: 1 new domain-specific heuristic, 6 usability goals, and coded clinicians' statements regarding ease of use for 10 sampled templates. Evaluators found 201 violations, a mean of 7...
August 2017: Journal of Medical Systems
https://www.readbyqxmd.com/read/28735365/an-update-on-the-use-of-immunotherapy-in-the-treatment-of-lymphoma
#6
REVIEW
Thomas U Marron, Matko Kalac, Joshua Brody
PURPOSE OF REVIEW: Throughout the field of oncology, immunotherapy is moving further towards the first-line setting, and there is encouraging data for the use of these novel therapies in the management of lymphomas, utilizing treatments approved for both solid and hematologic malignancies. Herein, we review promising advances in this rapidly moving field from the past year. RECENT FINDINGS: In the last year, we have seen promising clinical data on engineered antibody therapies for the treatment of lymphomas, as well as further optimization of engineered antibody fragments fused onto linkers or chimeric T cell receptors, both of the modalities capable of transforming non-specific T cells into tumor-specific, serial killer cells...
July 22, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28735028/protein-only-antimicrobial-peptide-containing-recombinant-nanoparticles-with-inherent-built-in-antibacterial-activity
#7
Naroa Serna, Laura Sánchez-García, Alejandro Sánchez-Chardi, Ugutz Unzueta, Mónica Roldán, Ramón Mangues, Esther Vázquez, Antonio Villaverde
The emergence of bacterial antibiotic resistances is a serious concern in human and animal health. In this context, naturally occurring cationic antimicrobial peptides (AMPs) might play a main role in a next generation of drugs against bacterial infections. Taking an innovative approach to design self-organizing functional proteins, we have generated here protein-only nanoparticles with intrinsic AMP microbicide activity. Using a recombinant version of the GWH1 antimicrobial peptide as building block, these materials show a wide antibacterial activity spectrum in absence of detectable toxicity on mammalian cells...
July 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28734899/strategies-to-develop-endogenous-stem-cell-recruiting-bioactive-materials-for-tissue-repair-and-regeneration
#8
Settimio Pacelli, Sayantani Basu, Jonathan Whitlow, Aparna R Chakravarti, Francisca Acosta, Arushi Varshney, Saman Modaresi, Cory Berkland, Arghya Paul
A leading strategy in tissue engineering is the design of biomimetic scaffolds that stimulate the body's repair mechanisms through the recruitment of endogenous stem cells to sites of injury. Approaches that employ the use of chemoattractant gradients to guide tissue regeneration without external cell sources are favored over traditional cell-based therapies that have limited potential for clinical translation. Following this concept, bioactive scaffolds can be engineered to provide a temporally and spatially controlled release of biological cues, with the possibility to mimic the complex signaling patterns of endogenous tissue regeneration...
July 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28733245/engineered-nanoparticles-for-the-detection-treatment-and-prevention-of-atherosclerosis-how-close-are-we
#9
REVIEW
Luong T H Nguyen, Aristo Muktabar, Jinkai Tang, Vinayak P Dravid, C Shad Thaxton, Subbu Venkatraman, Kee Woei Ng
Atherosclerosis is one of the leading causes of morbidity and mortality worldwide. Nanotechnology has provided the possibility of designing nanoparticles that can translocate through tissues and home in to atherosclerotic plaques to achieve desired diagnostic, therapeutic, theranostic or 'theralivery' outcomes. Although nanomedicine approaches have demonstrated exciting possibilities, clinical reality is still distant and challenges are aplenty, such as specificity of targeting and nanotoxicity. Nevertheless, developments in formulations, delivery strategies and experimental models over the coming years will generate new knowledge to define the true potential of this field...
July 18, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28733099/design-of-anatomical-population-based-and-patient-specific-radial-head-implants
#10
Emily A Lalone, Simon R Deluce, Hannah Shannon, Graham J W King, James A Johnson
PURPOSE: The objective of this study was to characterize the morphology of the radial head and design population-based anatomical and patient-specific radial head implants. METHODS: Computed tomography (CT) images of 50 normal cadaveric upper extremities (34 male, 16 female) were obtained using a 64-slice CT scanner. Surface models were ellipse-fitted and characterized. Using an intersurface distance mapping approach, the surface geometry of the population-based anatomical design (PB-An), 3 distinct patient-specific designs, and an existing axisymmetrical implant (Com-Axi) were compared with the native radial head and the overall surface mismatch was measured...
July 18, 2017: Journal of Hand Surgery
https://www.readbyqxmd.com/read/28732047/in-vivo-analysis-of-glaucoma-related-features-within-the-optic-nerve-head-using-enhanced-depth-imaging-optical-coherence-tomography
#11
Tiago S Prata, Flavio S Lopes, Vitor G Prado, Izabela Almeida, Igor Matsubara, Syril Dorairaj, Rafael L Furlanetto, Roberto M Vessani, Augusto Paranhos
Structural differences between optic nerve head (ONH) parameters in glaucomatous and non-glaucomatous eyes has been documented, however the association between such parameters in patients with different disease stages is yet to be elucidated. We investigated the relationship between different laminar and prelaminar ONH structures using enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT) in a population with and without glaucoma. In this observational case-control study, we prospectively enrolled healthy individuals and glaucomatous patients with different disease stages...
2017: PloS One
https://www.readbyqxmd.com/read/28730958/engineering-synergistically-active-and-bioavailable-cost-effective-medicines-for-neglected-tropical-diseases-the-role-of-excipients
#12
Dolores R Serrano, Aikaterini Lalatsa, M Auxiliadora Dea-Ayuela
Leishmaniasis is a neglected tropical disease responsible for the ninth largest disease burden in the world threatening 350 million people mostly in developing countries. The lack of efficacy, severe adverse effects, long duration, high cost and parenteral administration of the current therapies result in poor patient compliance and emergence of resistance. Leishmaniasis' unmet need for safer, affordable and more effective treatments is only partly addressed by today's global health product pipeline that focuses on products amenable to rapid clinical development, mainly by reformulating or repurposing existing drugs for new uses...
July 19, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730696/cd34-cells-seeded-in-collagen-scaffolds-promote-bone-formation-in-a-mouse-calvarial-defect-model
#13
Jens Hertweck, Ulrike Ritz, Hermann Götz, Patrick C Schottel, Pol Maria Rommens, Alexander Hofmann
Bone tissue engineering (BTE) holds promise for managing the clinical problem of large bone defects. However, clinical adoption of BTE is limited due to limited vascularization of constructs, which could be circumvented by pre-cultivation of osteogenic and endothelial derived cells in natural-based polymer scaffolds. However, until now not many studies compared the effect of mono- and cocultures pre-seeded in collagen before implantation. We utilized a mouse calvarial defect model and compared five groups of collagen scaffolds: a negative control of a collagen scaffold alone, a positive control treated with BMP-7, monocultures of either human osteoblasts (hOBs) or CD34+ cells, and a coculture of hOB and CD34(+) cells...
July 21, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28729866/cytokine-induced-killer-cells-as-pharmacological-tools-for-cancer-immunotherapy
#14
REVIEW
Xingchun Gao, Yajing Mi, Na Guo, Hao Xu, Lixian Xu, Xingchun Gou, Weilin Jin
Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3(+)CD56(+) natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28728997/sepsis-reconsidered-identifying-novel-metrics-for-behavioral-landscape-characterization-with-a-high-performance-computing-implementation-of-an-agent-based-model
#15
Chase Cockrell, Gary An
OBJECTIVES: Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28-50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Performance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models...
July 17, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28728978/anticancer-drug-loaded-quantum-dots-engineered-polymeric-nanoparticles-diagnosis-therapy-combined-approach
#16
D Belletti, G Riva, M Luppi, G Tosi, F Forni, M A Vandelli, B Ruozi, F Pederzoli
Primary Effusion Lymphoma (PEL) is an HHV-8-related non Hodgkin lymphoma localized in body cavities (as pleural, peritoneal and pericardial) presenting lymphomatous effusion that, until now, lack of an effective therapy. Curcumin was reported to display pro-apoptotic effect via the inhibition of the JAK/STAT pathway, that is overexpressed in PEL cells, as consequence of virus infection. The administration of curcumin is severely restricted by its physicochemical properties, mainly its low solubility in biological fluid and consequently low bioavailability...
July 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28726971/an-environment-for-guideline-based-decision-support-systems-for%C3%A2-outpatients-monitoring
#17
Elisa M Zini, Giordano Lanzola, Paolo Bossi, Silvana Quaglini
OBJECTIVES: We propose an architecture for monitoring outpatients that relies on mobile technologies for acquiring data. The goal is to better control the onset of possible side effects between the scheduled visits at the clinic. METHODS: We analyze the architectural components required to ensure a high level of abstraction from data. Clinical practice guidelines were formalized with Alium, an authoring tool based on the PROforma language, using SNOMED-CT as a terminology standard...
July 19, 2017: Methods of Information in Medicine
https://www.readbyqxmd.com/read/28726352/computational-design-of-a-specific-heavy-chain-%C3%AE%C2%BA-light-chain-interface-for-expressing-fully-igg-bispecific-antibodies
#18
K J Froning, A Leaver-Fay, X Wu, S Phan, L Gao, F Huang, A Pustilnik, M Bacica, K Houlihan, Q Chai, J R Fitchett, J Hendle, B Kuhlman, S J Demarest
The use of bispecific antibodies (BsAbs) to treat human diseases is on the rise. Increasingly complex and powerful therapeutic mechanisms made possible by BsAbs are being described in the literature and are spurring innovation of novel BsAb formats and methods for their production. The long-lived in vivo pharmacokinetics, optimal biophysical properties and potential effector functions of natural IgG monoclonal (and monospecific) antibodies has resulted in a push to generate fully IgG BsAb formats with the same quaternary structure as monoclonal IgGs...
July 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28725934/-scaffold-based-bone-tissue-engineering
#19
REVIEW
B M Holzapfel, M Rudert, D W Hutmacher
Tissue engineering provides the possibility of regenerating damaged or lost osseous structures without the need for permanent implants. Within this context, biodegradable and bioresorbable scaffolds can provide structural and biomechanical stability until the body's own tissue can take over their function. Additive biomanufacturing makes it possible to design the scaffold's architectural characteristics to specifically guide tissue formation and regeneration. Its nano-, micro-, and macro-architectural properties can be tailored to ensure vascularization, oxygenation, nutrient supply, waste exchange, and eventually ossification not only in its periphery but also in its center, which is not in direct contact with osteogenic elements of the surrounding healthy tissue...
July 19, 2017: Der Orthopäde
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#20
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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