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https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#1
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28434891/nanotechnology-based-therapeutic-modality-to-boost-anti-tumor-immunity-and-collapse-tumor-defense
#2
REVIEW
Xiaomeng Hu, Tingting Wu, Yuling Bao, Zhiping Zhang
Cancer is still the leading cause of death. While traditional treatments such as surgery, chemotherapy and radiotherapy play dominating roles, recent breakthroughs in cancer immunotherapy indicate that the influence of immune system on cancer development is virtually beyond our expectation. Manipulating the immune system to fight against cancer has been thriving in recent years. Further understanding of tumor anatomy provides opportunities to put a brake on immunosuppression by overcoming tumor intrinsic resistance or modulating tumor microenvironment...
April 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28434396/immunotherapy-in-hematologic-malignancies-past-present-and-future
#3
REVIEW
Annie Im, Steven Z Pavletic
The field of immunotherapy in cancer treatments has been accelerating over recent years and has entered the forefront as a leading area of ongoing research and promising therapies that have changed the treatment landscape for a variety of solid malignancies. Prior to its designation as the Science Breakthrough of the Year in 2013, cancer immunotherapy was active in the treatment of hematologic malignancies. This review provides a broad overview of the past, present, and potential future of immunotherapy in hematologic malignancies...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434270/what-is-stable-pain-control-a-prospective-longitudinal-study-to-assess-the-clinical-value-of-a-personalized-pain-goal
#4
Robin Fainsinger, Cheryl Nekolaichuk, Lara Fainsinger, Viki Muller, Lisa Fainsinger, Pablo Amigo, Amanda Brisebois, Sarah Burton-Macleod, Sunita Ghosh, Rebekah Gilbert, Yoko Tarumi, Vincent Thai, Gary Wolch
BACKGROUND: A universal consensus regarding standardized pain outcomes does not exist. The personalized pain goal has been suggested as a clinically relevant outcome measure. AIM: To assess the feasibility of obtaining a personalized pain goal and to compare a clinically based personalized pain goal definition versus a research-based study definition for stable pain. DESIGN: Prospective longitudinal descriptive study. MEASURES: The attending physician completed routine assessments, including a personalized pain goal and the Edmonton Classification System for Cancer Pain, and followed patients daily until stable pain control, death, or discharge...
April 1, 2017: Palliative Medicine
https://www.readbyqxmd.com/read/28434104/mullerian-dysgenesis-a-critical-review-of-the-literature
#5
REVIEW
Souzana Choussein, Dimitrios Nasioudis, Dimitrios Schizas, Konstantinos P Economopoulos
PURPOSE: To present an update of the genetic, clinical, diagnostic, and therapeutic aspects of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. METHODS: Studies were considered eligible if they have evaluated patients with MRKH syndrome. Eligible articles were identified by a search of MEDLINE bibliographical database from 1950 to August 2016. A purely descriptive approach was adopted concerning all outcomes examined by the individual studies. RESULTS: MRKH syndrome is defined as congenital aplasia of the upper vagina and impairment of uterine development in normal 46XX females...
April 22, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28433786/mucoadhesive-tetrahydrocannabinol-loaded-nlc-formulation-optimization-and-long-term-physicochemical-stability
#6
Ghaith Hommoss, Sung Min Pyo, Rainer H Müller
Tetrahydrocannabinol (THC) is used to treat pain in cancer patients. On the market there are mainly oral formulations. Especially to treat the problematic breakthrough pain in cancer, an easy applicable formulation with fast onset is desired. This formulation was developed as an aqueous nasal spray using nanostructured lipid carriers (NLC). The NLC were prepared with cetyl palmitate, having good miscibility with the oily THC and yielding particles with 1 year physical long-term stability. To make the particles mucoadhesive, small particles with diameters of about 200 nm were produced and additionally their surface positively charged using a cationic stabilizer...
April 19, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28433330/bivalent-rlp2086-trumenba%C3%A2-development-of-a-well-characterized-vaccine-through-commercialization
#7
Khurram Sunasara, John Cundy, Sriram Srinivasan, Brad Evans, Weiqiang Sun, Scott Cook, Eric Bortell, John Farley, Daniel Griffin, Michele Bailey Piatchek, Katherine Arch-Douglas
The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation...
April 19, 2017: Vaccine
https://www.readbyqxmd.com/read/28432833/cellular-and-humoral-immunity-after-vaccination-or-natural-infection-of-mumps
#8
Kihei Terada, Kimiko Hagihara, Tomohiro Oishi, Ippei Miyata, Hiroto Akaike, Satoko Ogita, Naoki Ohno, Kazunobu Ouchi
OBJECTIVE: This study measured cell-mediated immunity (CMI) and serum antibody levels to clarify the basis of breakthrough after vaccination and reinfection after mumps. METHODS: From a pool of 54 college students, 17 seronegative subjects and 14 subjects with intermediate levels of antibodies against mumps were vaccinated with a monovalent mumps vaccine and CMI was assessed using an interferon-γ release assay. RESULTS: CMI positivity in subjects classified by pre-existing antibody levels, which gave groups with titers of <2...
April 22, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28432287/advantages-of-unfair-quantum-ground-state-sampling
#9
Brian Hu Zhang, Gene Wagenbreth, Victor Martin-Mayor, Itay Hen
The debate around the potential superiority of quantum annealers over their classical counterparts has been ongoing since the inception of the field. Recent technological breakthroughs, which have led to the manufacture of experimental prototypes of quantum annealing optimizers with sizes approaching the practical regime, have reignited this discussion. However, the demonstration of quantum annealing speedups remains to this day an elusive albeit coveted goal. We examine the power of quantum annealers to provide a different type of quantum enhancement of practical relevance, namely, their ability to serve as useful samplers from the ground-state manifolds of combinatorial optimization problems...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430547/enhancing-insights-into-pulmonary-vascular-disease-pvd-through-a-precision-medicine-approach-a-joint-nhlbi-cmref-workshop-report
#10
John H Newman, Stuart Rich, Steven H Abman, John H Alexander, John Barnard, Gerald J Beck, Raymond L Benza, Todd M Bull, Stephen Y Chan, Hyung J Chun, Declan Doogan, Jocelyn Dupuis, Serpil C Erzurum, Robert P Frantz, Mark Geraci, Hunter Gillies, Mark Gladwin, Michael P Gray, Anna R Hemnes, Roy S Herbst, Adrian F Hernandez, Nicholas S Hill, Evelyn M Horn, Kendall Hunter, Zhi-Cheng Jing, Roger Johns, Sanjay Kaul, Steven M Kawut, Tim Lahm, Jane A Leopold, Greg D Lewis, Stephen C Mathai, Vallerie V McLaughlin, Evangelos D Michelakis, Steven D Nathan, William Nichols, Grier Page, Marlene Rabinovitch, Jonathan Rich, Franz Rischard, Sharon Rounds, Sanjiv J Shah, Victor F Tapson, Naomi Lowy, Norman Stockbridge, Gail Weinmann, Lei Xiao
The Division of Lung Diseases of the National Heart, Lung and Blood Institute, (NHLBI) and the Cardiovascular Medical Education and Research Fund (CMREF), held a workshop to discuss to leverage of the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension (PH) through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program. PVDOMICS is a protocol driven network to analyze PH patient populations to define novel pulmonary vascular disease (PVD) phenotypes. Basic, translational and clinical investigators, patient advocacy organizations, regulatory agencies, and pharmaceutical industry experts discussed the application of precision medicine to PVD clinical trials...
April 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28430535/transcranial-focused-ultrasound-a-new-tool-for-non-invasive-neuromodulation
#11
Maria Fini, William J Tyler
Ultrasound (US) is widely known for its utility as a biomedical imaging modality. An abundance of evidence has recently accumulated showing that US is also useful for non-invasively modulating brain circuit activity. Through a series of studies discussed in this short review, it has recently become recognized that transcranial focused ultrasound can exert mechanical (non-thermal) bioeffects on neurons and cells to produce focal changes in the activity of brain circuits. In addition to highlighting scientific breakthroughs and observations that have driven the development of the field of ultrasonic neuromodulation, this study also provides a discussion of mechanisms of action underlying the ability of ultrasound to physically stimulate and modulate brain circuit activity...
April 21, 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/28428506/-a-new-therapeutic-approach-for-cancer-related-breakthrough-pain-focused-on-oral-transmucosal-fentanyl
#12
Kinomi Yomiya, Masayuki Kaneshima, Beni Kyosaka, Etsuko Warita, Rie Hosonuma, Shinnosuke Osato
In 2013, oral transmucosal fentanyl was first approved in Japan for reducing breakthrough pain(BTP). The development of BTP may contribute to less-effective analgesia, a reduced satisfaction with analgesia therapy, obstacles in daily life, mood disorders, and an increased use of healthcare resources. In most BTP, both the duration from BTP onset to its maximum intensity and the overall duration of BTP episodes are relatively short. The need for improved rapid pain relief for BTP in this setting has led to the development of rapid-onset opioids(ROOs), including oral transmucosal fentanyl citrate(OTFC)...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28426649/the-importance-of-appropriate-initial-bacterial-colonization-of-the-intestine-in-newborn-child-and-adult-health
#13
REVIEW
W Allan Walker
The fetus does not reside in a sterile intrauterine environment and is exposed to commensal bacteria from the maternal gut/blood stream which crosses the placenta and enters the amniotic fluid. This intestinal exposure to colonizing bacteria continues at birth and during the first year of life and has a profound influence on lifelong health. Why is this important? Intestinal crosstalk with colonizing bacteria in the developing intestine affects the infant's adaptation to extrauterine life (immune homeostasis) and provides protection against disease expression (allergy, autoimmune disease, obesity, etc...
April 20, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28422487/stepwise-deoxygenation-of-nitrite-as-a-route-to-two-families-of-ruthenium-corroles-group-8-periodic-trends-and-relativistic-effects
#14
Abraham B Alemayehu, Hugo Vazquez-Lima, Kevin J Gagnon, Abhik Ghosh
Given the many applications of ruthenium porphyrins, the rarity of ruthenium corroles and the underdeveloped state of their chemistry are clearly indicative of an area ripe for significant breakthroughs. The tendency of ruthenium corroles to form unreactive metal-metal-bonded dimers has been recognized as a key impediment in this area. Herein, by exposing free-base meso-tris(p-X-phenyl)corroles, H3[TpXPC] (X = CF3, H, Me, and OMe), and [Ru(COD)Cl2]x in refluxing 2-methoxyethanol to nitrite, we have been able to reliably intercept the series Ru[TpXPC](NO) in a matter of seconds to minutes and subsequently Ru(VI)[TpXPC](N), the products of a second deoxygenation, over some 16 h...
April 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28421494/chapter-10-human-oocyte-vitrification
#15
Laura Rienzi, Ana Cobo, Filippo Maria Ubaldi
Discovery and widespread application of successful cryopreservation methods for MII-phase oocytes was one of the greatest successes in human reproduction during the past decade. Although considerable improvements in traditional slow-rate freezing were also achieved, the real breakthrough was the result of introduction of vitrification. Here we describe the method that is most commonly applied for this purpose, provides consistent survival and in vitro developmental rates, results in pregnancy and birth rates comparable to those achievable with fresh oocytes, and does not result in higher incidence of gynecological or postnatal complications...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28421031/fatal-outcome-of-european-tick-borne-encephalitis-after-vaccine-failure
#16
Parham Sendi, Cédric Hirzel, Stefan Pfister, Rahel Ackermann-Gäumann, Denis Grandgirard, Ekkehard Hewer, Arto C Nirkko
Tick-borne encephalitis is a viral disease affecting the central nervous system. It is endemic in Switzerland with 200-250 notified cases annually. Active immunization is effective for persons in all age groups. Vaccine failure is rare, in particular after a completed vaccination course. Here, we describe the case of 67-year-old man with a fatal outcome despite vaccination. The diagnosis was confirmed by extensive postmortem analyses. The diagnostic challenges of vaccine failure in tick-borne encephalitis and the dynamics of the immune response in vaccination breakthrough are discussed...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28420989/fda-facilitated-regulatory-pathways-visualizing-their-characteristics-development-and-authorization-timelines
#17
Lawrence Liberti, Magda Bujar, Alasdair Breckenridge, Jarno Hoekman, Neil McAuslane, Pieter Stolk, Hubert Leufkens
The US Food and Drug Administration (FDA) has four facilitated regulatory pathways (FRPs): Fast Track (FT), Breakthrough Therapy (BTD), Priority Review (PR), and Accelerated Approval (AA). Only PR specifies an expedited review timeline (6 months). We sought to determine to what extent the combination of two or more FRPs influenced development and approval times. We developed a "metro map" to illustrate FRP elements and their influence on review times. We assessed 125 new active substances (approved January 2013 to December 2015) 74 of which used one or more FRPs...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28420529/separation-of-antibody-monomer-dimer-mixtures-by-frontal-analysis
#18
Jason M Reck, Timothy M Pabst, Alan K Hunter, Giorgio Carta
The removal of aggregates, particularly soluble dimers, from monoclonal antibodies (mAbs) remains a persistent challenge in downstream processing. In this work, we have examined the separation of an antibody monomer from its dimer on the cation exchange resin Nuvia HR-S (Bio-Rad Laboratories) using frontal analysis. In this process, a mixture of monomer and dimer is continuously fed to the column under conditions where the mixture is favorably bound, resulting in two breakthrough fronts whose monomer and dimer compositions are determined by the multi-component equilibrium and kinetics of the system...
April 10, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28419986/hypodysfibrinogenemia-with-a-heterozygous-mutation-of-%C3%AE-cys326ser-by-the-novel-transversion-of-tgt-to-tct-in-a-patient-with-pulmonary-thromboembolism-and-right-ventricular-thrombus
#19
Akiko Ushijima, Taichi Komai, Atsuko Masukawa, Keiko Oikawa, Norishige Morita, Satomi Asai, Saki Mukai, Nobuo Okumura, Yoshinori Kobayashi, Hayato Miyachi
We encountered a 45-year-old Japanese man who suffered from pulmonary thromboembolism and huge right ventricular thrombus after inferior vena cava (IVC) filter implantation without apparent thrombus in either the deep veins or inside the IVC filter. The biochemical data showed a discrepancy in the level of fibrinogen between the immunological and thrombin time methods, suggesting hypodysfibrinogenemia. The sequencing of the fibrinogen γ-chain gene (FGG) revealed a novel heterozygous missense mutation in exon 8 - a TGT to TCT transversion in codon 326 - resulting in an amino acid substitution of serine for cysteine (γCys326Ser)...
April 19, 2017: Cardiology
https://www.readbyqxmd.com/read/28419835/the-architecture-and-function-of-the-chromatin-replication-machinery
#20
REVIEW
Thomas Cr Miller, Alessandro Costa
Genomic DNA in eukaryotic cells is packaged into nucleosome arrays. During replication, nucleosomes need to be dismantled ahead of the advancing replication fork and reassembled on duplicated DNA. The architecture and function of the core replisome machinery is now beginning to be elucidated, with recent insights shaping our view on DNA replication processes. Simultaneously, breakthroughs in our mechanistic understanding of epigenetic inheritance allow us to build new models of how histone chaperones integrate with the replisome to reshuffle nucleosomes...
April 15, 2017: Current Opinion in Structural Biology
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