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https://www.readbyqxmd.com/read/28637024/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#1
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636480/the-emerging-role-of-pimavanserin-in-the-management-of-parkinson-s-disease-psychosis
#2
Neal Hermanowicz, Gustavo Alva, Fernando Pagan, Alberto J Espay, Amita Patel, Katya Cruz Madrid, Daniel Kremens, Jim Kenney, Sheila Arquette, Gary Tereso, Maria Lopes, Carolyn Farnum
A panel of experts drawn from neurology, psychiatry, geropsychiatry, geriatrics, and pharmacy representatives of 3 health plans convened in New York City on July 30, 2016, with the objective of sharing opinions, ideas, and information regarding the optimal management of Parkinson's disease psychosis (PDP). Three key points emerged from the discussion: (1) Because of the nature of Parkinson's disease and PDP, finding appropriate treatment can prove challenging; (2) emerging therapies may present an opportunity for effective disease management; and (3) moving forward, provider and patient education regarding PDP and available treatment options is essential for well-managed symptoms and better quality of life...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#3
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635659/divergent-how-ige-axis-contributes-to-the-continuum-of-allergic-asthma-and-anti-ige-therapies
#4
REVIEW
Óscar Palomares, Silvia Sánchez-Ramón, Ignacio Dávila, Luis Prieto, Luis Pérez de Llano, Marta Lleonart, Christian Domingo, Antonio Nieto
Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28634151/speech-and-swallowing-abnormalities-in-adults-with-polg-associated-ataxia-polg-a
#5
Adam P Vogel, Natalie Rommel, Andreas Oettinger, Marius Horger, Patrick Krumm, Eva-Maria Kraus, Ludger Schöls, Matthis Synofzik
BACKGROUND: Mutations in the nuclear-encoded mitochondrial DNA polymerase gamma (POLG) can result in a wide spectrum of neurological deficits. A common presentation is progressive ataxia (POLG-A) which includes impaired speech and swallowing. The nature, severity and impact of these deficits in POLG-A is not known. A comprehensive quantitative and qualitative characterization of dysarthria and dysphagia in this recurrent ataxia disorder will assist in diagnostics, provide insights into the underlying pathology, and establish the foundation for future therapy trials...
June 17, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#6
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28634032/ciclosporin-use-in-epidermal-necrolysis-is-associated-with-an-important-mortality-reduction-evidence-from-three-different-approaches
#7
C González-Herrada, S Rodríguez-Martín, L Cachafeiro, V Lerma, O González, J A Lorente, A Rodríguez-Miguel, J González-Ramos, G Roustan, E Ramírez, T Bellón, F J de Abajo
Several immunomodulatory agents are used in the treatment of Epidermal Necrolysis (EN), but evidence of their efficacy is limited. The Autonomous Community of Madrid has two reference Burn Units (BUs) to which all patients with EN are referred to. One BU has mostly used ciclosporin (CsA), while the other has used non-CsA therapies (mainly high-dose intravenous immunoglobulin). The allocation of patients to one or another BU was mainly based on proximity resembling a random assignment. Thus, we took advantage of this "natural experiment" to estimate the mortality risk ratio (MRR) of CsA (N=26) as compared to non-CsA (n=16) using hospital as an instrumental variable (IV) over the period 2001-2015...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28633979/zerumbone-modulates-cd1d-expression-and-lipid-antigen-presentation-pathway-in-breast-cancer-cells
#8
Ritis K Shyanti, Anuradha Sehrawat, Shivendra V Singh, J P N Mishra, Rana P Singh
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28633821/enhanced-production-of-hypocrellin-a-by-ultrasound-stimulation-in-submerged-cultures-of-shiraia-bambusicola
#9
Chun Xiao Sun, Yan Jun Ma, Jian Wen Wang
Hypocrellin A (HA), a naturally occurring fungal perylenequinone, is widely used in clinic to treat skin diseases and developed as a photodynamic therapy (PDT) agent against cancers. In this study, a low intensity ultrasound (US, 0.28W/cm(2) at 40kHz) was conducted thrice of repeated US exposure (5-min) with an interval of 12h to stimulate HA production of Shiraia bambusicola after 72h of the initial submerged cultures. US not only increased the content of HA by 177.2% in mycelia, but stimulated the release of HA into the medium with the highest total production of HA (247...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28633665/optimizing-bronchodilation-in-the-prevention-of-copd-exacerbations
#10
REVIEW
Marc Miravitlles, Antonio Anzueto, José R Jardim
The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments...
June 20, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#11
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28633044/written-accounts-of-living-with-psychogenic-nonepileptic-seizures-a-thematic-analysis
#12
Gregg H Rawlings, Ian Brown, Brendan Stone, Markus Reuber
PURPOSE: Qualitative studies examining lived experiences of psychogenic nonepileptic seizures (PNES) have predominantly relied on datasets collected using clinical or research interviews. This study pursued a different approach by investigating individuals' written accounts of their condition. METHODS: Participants (n=19) were recruited from membership-led organisations for individuals living with seizures and from a United Kingdom hospital. Participants were instructed to produce four pieces of writing: 1) about their thoughts and feelings about their condition; 2) a letter to their condition; 3) a letter to their younger self; and 4) about a personal value...
June 15, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#13
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28631904/-analysis-of-factors-affecting-the-compliance-with-medical-therapy-for-benign-prostatic-hyperplasia
#14
V A Malkhasyan, P I Rasner, A R Gevorkyan, I V Semenyakin, A V Tedeev, D Yu Pushkar
AIM: To investigate factors affecting the compliance of patients with the combination therapy for benign prostatic hyperplasia. MATERIALS AND METHODS: Four hundred BPH outpatients treated with combination therapy were surveyed. RESULTS: The absolute majority of patients (76.16%) expected a quick positive result. 10.47% viewed their disease as too advanced, did not believe in the effectiveness of medical therapy and believed the surgery to be the only treatment option...
June 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28630894/next-generation-probes-particles-and-proteins-for-neural-interfacing
#15
REVIEW
Jonathan Rivnay, Huiliang Wang, Lief Fenno, Karl Deisseroth, George G Malliaras
Bidirectional interfacing with the nervous system enables neuroscience research, diagnosis, and therapy. This two-way communication allows us to monitor the state of the brain and its composite networks and cells as well as to influence them to treat disease or repair/restore sensory or motor function. To provide the most stable and effective interface, the tools of the trade must bridge the soft, ion-rich, and evolving nature of neural tissue with the largely rigid, static realm of microelectronics and medical instruments that allow for readout, analysis, and/or control...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630875/contribution-of-the-microenvironmental-niche-to-glioblastoma-heterogeneity
#16
REVIEW
Ivy A W Ho, Winston S N Shim
Glioblastoma is the most aggressive cancer of the brain. The dismal prognosis is largely attributed to the heterogeneous nature of the tumor, which in addition to intrinsic molecular and genetic changes is also influenced by the microenvironmental niche in which the glioma cells reside. The cancer stem cells (CSCs) hypothesis suggests that all cancers arise from CSCs that possess the ability to self-renew and initiate tumor formation. CSCs reside in specialized niches where interaction with the microenvironment regulates their stem cell behavior...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28630851/vacuum-assisted-closure-in-patients-with-post-operative-infections-after-instrumented-spine-surgery-a-series-of-12-cases
#17
Maya Kale, Pravin Padalkar, Varshil Mehta
INTRODUCTION: Post-operative wound infections after spinal surgery is a very serious problem, leading to a risk of significant morbidity which may even lead to prolonged hospitalization. Various treatment protocols have been recommended for debridement, antibiotic, and soft-tissue management, but with mixed results. However, the risk of morbidity is still high with these treatment options. Vacuum-assisted closure (VAC) system has been gaining popularity recently in the management of subacute, acute, and chronic wounds...
January 2017: Journal of Orthopaedic Case Reports
https://www.readbyqxmd.com/read/28630440/looking-to-nature-for-a-new-concept-in-antimicrobial-treatments-isoflavonoids-from-cytisus-striatus-as-antibiotic-adjuvants-against-mrsa
#18
Ana Cristina Abreu, Aline Coqueiro, Andi R Sultan, Nicole Lemmens, Hye Kyong Kim, Robert Verpoorte, Willem J B van Wamel, Manuel Simões, Young Hae Choi
The spread of multidrug-resistant Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA), has shortened the useful life of anti-staphylococcal drugs enormously. Two approaches can be followed to address this problem: screening various sources for new leads for antibiotics or finding ways to disable the resistance mechanisms to existing antibiotics. Plants are resistant to most microorganisms, but despite extensive efforts to identify metabolites that are responsible for this resistance, no substantial progress has been made...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630188/identification-of-a-novel-antibacterial-compound-1-2-4-dichlorophenethyl-amino-3-phenoxypropan-2-ol-active-against-persisters-of-pseudomonas-aeruginosa
#19
Veerle Liebens, Valerie Defraine, Wouter Knapen, Toon Swings, Serge Beullens, Romu Corbau, Arnaud Marchand, Patrick Chaltin, Maarten Fauvart, Jan Michiels
Antibiotics typically fail to completely eradicate a bacterial population, leaving a small fraction of transiently antibiotic-tolerant persister cells intact. Persisters are therefore seen as a major cause of treatment failure and greatly contribute to the recalcitrant nature of chronic infections. The current report is focused on Pseudomonas aeruginosa, a Gram-negative pathogen belonging to the notorious ESKAPE group and, due to an increasing resistance against most conventional antibiotics, posing a serious threat to human health...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28629226/no-significant-impact-of-foxf1-sirna-treatment-in-acute-and-chronic-ccl4-liver-injury
#20
Kerstin Abshagen, Tobias Rotberg, Berit Genz, Brigitte Vollmar
Chronic liver injury of any etiology is the main trigger of fibrogenic responses and thought to be mediated by hepatic stellate cells. Herein, activating transcription factors like forkhead box f1 are described to stimulate pro-fibrogenic genes in hepatic stellate cells. By using a liver-specific siRNA delivery system (DBTC), we evaluated whether forkhead box f1 siRNA treatment exhibit beneficial effects in murine models of acute and chronic CCl4-induced liver injury. Systemic administration of DBTC-forkhead box f1 siRNA in mice was only sufficient to silence forkhead box f1 in acute CCl4 model, but was not able to attenuate liver injury as measured by liver enzymes and necrotic liver cell area...
January 1, 2017: Experimental Biology and Medicine
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