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https://www.readbyqxmd.com/read/29156850/harness-the-synergy-between-targeted-therapy-and-immunotherapy-what-have-we-learned-and-where-are-we-headed
#1
REVIEW
Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#2
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156642/is-the-benefit-risk-ratio-for-patients-with-transfusion-dependent-thalassemia-treated-by-unrelated-cord-blood-transplantation-favorable
#3
REVIEW
Tang-Her Jaing
Transfusion-dependent thalassemia (TDT) is an inherited disorder characterized by absent or defective production of α- or β-hemoglobin chains. If untreated, the disease invariably culminates in death in early infancy due to cardiac failure or overwhelming infection. Although there is clear evidence of good health-related quality of life and return to normal life style, the choice to undergo hematopoietic stem cell transplantation (HSCT) remains a challenge because of the potential risk of transplant-related mortality (TRM) in TDT...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156169/next-generation-minimal-resection-fixed-bearing-total-ankle-replacement-indications-and-outcomes
#4
REVIEW
Justin Tsai, David I Pedowitz
Total ankle arthroplasty is an increasingly popular procedure to address tibiotalar joint arthritis. Implant design and the rationale behind it have changed throughout the years. Newer generation implants allow for minimal resection of bone and use fixed-bearing technology. Long-term follow-up multicenter studies will determine the lifetime of these devices and their effectiveness in addressing pain and improving function for patients with endstage tibiotalar arthritis.
January 2018: Clinics in Podiatric Medicine and Surgery
https://www.readbyqxmd.com/read/29155182/inspector-perceptions-of-the-food-and-drug-administration-s-newest-recommended-food-facility-inspection-format-training-matters
#5
Jing Ma, Jooho Kim, Barbara Almanza
The Food and Drug Administration publishes the Food Code to guide restaurant inspections. The most recent version proposes a three-tier system categorizing violations as priority, priority foundation, and core. This study used a scenario-based questionnaire to examine inspector perceptions and preferences for inspection formats. Results suggest that inspectors would be able to maintain consistent evaluations when changing to the three-tier system, although the classifying terms under the three-tier system were confusing...
June 2017: Journal of Environmental Health
https://www.readbyqxmd.com/read/29154989/targeting-bromodomain-and-extraterminal-proteins-in-breast-cancer
#6
REVIEW
Jennifer M Sahni, Ruth A Keri
Breast cancer is a collection of distinct tumor subtypes that are driven by unique gene expression profiles. These transcriptomes are controlled by various epigenetic marks that dictate which genes are expressed and suppressed. During carcinogenesis, extensive restructuring of the epigenome occurs, including aberrant acetylation, alteration of methylation patterns, and accumulation of epigenetic readers at oncogenes. As epigenetic alterations are reversible, epigenome-modulating drugs could provide a mechanism to silence numerous oncogenes simultaneously...
November 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29153882/identification-of-probiotic-effector-molecules-present-state-and-future-perspectives
#7
REVIEW
Sarah Lebeer, Peter A Bron, Maria L Marco, Jan-Peter Van Pijkeren, Mary O'Connell Motherway, Colin Hill, Bruno Pot, Stefan Roos, Todd Klaenhammer
Comprehension of underlying mechanisms of probiotic action will support rationale selection of probiotic strains and targeted clinical study design with a higher likelihood of success. This will consequently contribute to better substantiation of health claims. Here, we aim to provide a perspective from a microbiology point of view that such comprehensive understanding is not straightforward. We show examples of well-documented probiotic effector molecules in Lactobacillus and Bifidobacterium strains, including surface-located molecules such as specific pili, S-layer proteins, exopolysaccharides, muropeptides, as well as more widely produced metabolites such as tryptophan-related and histamine-related metabolites, CpG-rich DNA, and various enzymes such as lactase and bile salt hydrolases...
November 15, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29153871/revisiting-the-impact-of-macroeconomic-conditions-on-health-behaviours
#8
Giorgio Di Pietro
This paper estimates the average population effect of macroeconomic conditions on health behaviours accounting for the heterogeneous impact of the business cycle on individuals. While previous studies use models relying on area-specific unemployment rates to estimate this average effect, this paper employs a model based on area-specific unemployment rates by gender and age group. The rationale for breaking down unemployment rates is that the severity of cyclical upturns and downturns does not only significantly vary across geographical areas, but also across gender and age...
November 7, 2017: Economics and Human Biology
https://www.readbyqxmd.com/read/29151853/in-situ-conservation-harnessing-natural-and-human-derived-evolutionary-forces-to-ensure-future-crop-adaptation
#9
REVIEW
Mauricio R Bellon, Ehsan Dulloo, Julie Sardos, Imke Thormann, Jeremy J Burdon
Ensuring the availability of the broadest possible germplasm base for agriculture in the face of increasingly uncertain and variable patterns of biotic and abiotic change is fundamental for the world's future food supply. While ex situ conservation plays a major role in the conservation and availability of crop germplasm, it may be insufficient to ensure this. In situ conservation aims to maintain target species and the collective genotypes they represent under evolution. A major rationale for this view is based on the likelihood that continued exposure to changing selective forces will generate and favor new genetic variation and an increased likelihood that rare alleles that may be of value to future agriculture are maintained...
December 2017: Evolutionary Applications
https://www.readbyqxmd.com/read/29151656/unmarried-mothers-postnatal-school-enrollment-the-role-and-intersection-of-demographic-and-socioeconomic-characteristics
#10
Melissa Radey
Drawing from a theoretical model of educational decisions and intersectionality theory, this study examined demographic, socioeconomic, and public assistance characteristics that influence unmarried mothers' postnatal enrollment. Using the Fragile Families and Child Wellbeing Study (FFCWS), binomial and multinomial regression techniques were used to examine unmarried mothers' enrollment in their child's first nine years. Results showed unmarried mothers' educational commitment coupled with the influence of race and class indicate that they need additional opportunities to optimize their educations and job opportunities...
2017: Journal of Social Service Research
https://www.readbyqxmd.com/read/29151001/intravenous-fluid-therapy-for-hospitalized-and-critically-ill-children-rationale-available-drugs-and-possible-side-effects
#11
Thomas Langer, Rosamaria Limuti, Concezione Tommasino, Niels van Regenmortel, Els L I M Duval, Pietro Caironi, Manu L N G Malbrain, Antonio Pesenti
Human beings are constituted mainly of water. In particular, children's total body water might reach 75-80% of their body weight, compared to 60-70% in adults. It is therefore not surprising, that children, especially hospitalized newborns and infants, are markedly prone to water and electrolyte imbalances. Parenteral fluid therapy is a cornerstone of medical treatment and is thus of exceptional relevance in this patient population. It is crucial to appreciate the fact that intravenous fluids are drugs with very different characteristics, different indications, contraindications and relevant side effects...
November 18, 2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/29150969/non-operative-treatment-as-a-strategy-for-patients-with-parastomal-hernia-a-multicentre-retrospective-cohort-study
#12
L F Kroese, D P V Lambrichts, J Jeekel, G J Kleinrensink, A G Menon, E J R de Graaf, W A Bemelman, J F Lange
AIM: Parastomal hernia is the most common complication following stoma construction. Surgical treatment is usually chosen over non-operative treatment, but a clear rationale for the choice of management is often lacking. This study aims to investigate the reasons for non-operative treatment, cross-over rates, and postoperative complications. METHOD: A multicentre, retrospective cohort study was conducted. Patients diagnosed with a parastomal hernia between January 2007 and December 2012 were included...
November 18, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/29150474/core-outcome-sets-in-miscarriage-trials-cosmist-study-a-study-protocol
#13
Paul Smith, Natalie Cooper, Rima Dhillon-Smith, Emily O'Toole, T Justin Clark, Arri Coomarasamy
INTRODUCTION: 'Core outcome sets' are an agreed, standardised set of outcomes based on what key stakeholders (clinicians, patients, their partners, researchers, service developers, funding organisations and so on) consider the important outcomes in the management or prevention of a condition. This paper describes the rationale and design for the development of Core Outcome Sets for Miscarriage Trials. METHODS AND ANALYSIS: Systematic reviews, interviews and focus groups with patients and their partners will be conducted to identify potential core outcomes that will be introduced into a modified Delphi survey...
November 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29150330/the-structural-requirements-of-histone-deacetylase-inhibitors-c4-modified-saha-analogs-display-dual-hdac6-hdac8-selectivity
#14
Ahmed T Negmeldin, Joseph R Knoff, Mary Kay H Pflum
Histone deacetylase (HDAC) enzymes govern the post-translational acetylation state of lysine residues on protein substrates, leading to regulatory changes in cell function. Due to their role in cancers, HDAC proteins have emerged as promising targets for cancer treatment. Four HDAC inhibitors have been approved as anti-cancer therapeutics, including SAHA (Suberoylanilide hydroxamic acid, Vorinostat, Zolinza). SAHA is a nonselective HDAC inhibitor that targets most of the eleven HDAC isoforms. The nonselectivity of SAHA might account for its clinical side effects, but certainly limits its use as a chemical tool to study cancer-related HDAC cell biology...
October 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29150287/anastasis-and-the-er-stress-response-solving-the-paradox-of-the-unfolded-protein-response-in-cancer
#15
Rafael Vincent M Manalo
In recent years, studies have suggested a novel pathway for cell survival, which faces scientific skepticism and interest in its concept of cell 'resurrection' - that is, the anastasis of cells at late-stage apoptosis. While biomarkers have been discovered, many of these are related to the endoplasmic reticulum (ER) stress response - acting also to promote cell survival in the presence of perturbation. The promises of anastasis, if accepted, will greatly impact translational medicine especially in the treatment of cancer, since apoptosis is generally irreversible in the late stages, and chemotherapy is performed to maximize tumor death and minimize off-target effects...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149944/management-of-sepsis-induced-immunosuppression
#16
REVIEW
Fabienne Venet, Thomas Rimmelé, Guillaume Monneret
It is now well established that profound immunosuppression develops within a few days after sepsis onset in patients. This should be considered additional organ failure because it is associated with increased rate of nosocomial infections, mortality, and long-term complications, thus constituting the rationale for immunomodulation in patients. Nevertheless, the demonstration of the efficacy of such therapeutic strategy in improving deleterious outcomes in sepsis remains to be made. Results from clinical trials based on interleukin 7 and granulocyte macrophage colony-stimulating factor immunoadjuvant therapies in septic shock patients are expected for 2018...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149368/dietary-guidance-for-lutein-consideration-for-intake-recommendations-is-scientifically-supported
#17
Katherine M Ranard, Sookyoung Jeon, Emily S Mohn, James C Griffiths, Elizabeth J Johnson, John W Erdman
Lutein, a yellow xanthophyll carotenoid found in egg yolks and many colorful fruits and vegetables, has gained public health interest for its putative role in visual performance and reducing the risk of age-related macular degeneration. The National Academies of Sciences, Engineering and Medicine's recommended Dietary Reference Intakes (DRIs) focus on preventing deficiency and toxicity, but there is a budding interest in establishing DRI-like guidelines for non-essential bioactives, like lutein, that promote optimal health and/or prevent chronic diseases...
November 17, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29149330/s101-an-inhibitor-of-proliferating-t-cells-rescues-mice-from-superantigen-induced-shock
#18
Alexei Shir, Shoshana Klein, Idit Sagiv-Barfi, Tamar Geiger, Maya Zigler, Yael Langut, Nufar Edinger, Alexander Levitzki
Superantigens (SAg) are extremely potent bacterial toxins, which evoke a virulent immune response, inducing non-specific T-cell proliferation, rapid cytokine release and lethal toxic shock, for which there is no effective treatment. We previously developed a small molecule, S101, which potently inhibits proliferating T-cells (Sagiv-Barfi et al, Bioorg Med Chem (2010) 18:6404-6413). In a severe mouse model of toxic shock, a single injection of S101 given together with superantigen challenge, rescued 100% of the mice...
November 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29149249/human-accelerated-regions-and-other-human-specific-sequence-variations-in-the-context-of-evolution-and-their-relevance-for-brain-development
#19
Anastasia Levchenko, Alexander Kanapin, Anastasia Samsonova, Raul Gainetdinov
The review discusses, in a format of a timeline, the studies of different types of genetic variants, present in Homo sapiens, but absent in all other primate, mammalian or vertebrate species, tested so far. The main characteristic of these variants is that they are found in regions of high evolutionary conservation. These sequence variations include single nucleotide substitutions (called human accelerated regions), deletions and segmental duplications. The rationale for finding such variations in the human genome is that they could be responsible for traits, specific to our species, of which the human brain is the most remarkable...
November 14, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29148725/chromophore-isomer-stabilization-is-critical-to-efficient-fluorescence-in-cyan-fluorescent-proteins
#20
Guillaume Gotthard, David von Stetten, Damien Clavel, Marjolaine Noirclerc-Savoye, Antoine Royant
ECFP, the first usable Cyan Fluorescent Protein, was obtained by adapting the tyrosine-based chromophore environment in Green Fluorescent Protein to that of a tryptophan-based one. This 1(st)-generation CFP was superseded by the popular Cerulean, CyPet and SCFP3A that were engineered by rational and random mutagenesis. Yet, the latter CFPs still exhibit suboptimal properties of pH sensitivity and reversible photobleaching behavior. These flaws were serendipitously corrected in the 3(rd)-generation CFP mTurquoise and its successors without obvi-ous rationale...
November 17, 2017: Biochemistry
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