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https://www.readbyqxmd.com/read/28822887/the-changing-diagnostic-pathway-for-lung-cancer-patients-in-shanghai-china
#1
REVIEW
Tao Jiang, Shengxiang Ren, Xuefei Li, Chunxia Su, Caicun Zhou, Mary O'Brien
Accumulating evidence suggest that patients with advanced non-small-cell lung cancer (NSCLC) and specific genomic alterations including epidermal growth factor receptor and microtubule-associated protein-like 4 anaplastic lymphoma kinase could significantly benefit from molecular-targeted therapies compared with chemotherapy. Recently, immunotherapy based on programmed cell death 1 (PD-1) and its ligand (PD-L1) blockade prolong survival in patients with advanced NSCLC, especially in those patients with positive expression of PD-L1 and when used in the first-line setting...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28822576/pembrolizumab-versus-ipilimumab-for-advanced-melanoma-final-overall-survival-results-of-a-multicentre-randomised-open-label-phase-3-study-keynote-006
#2
Jacob Schachter, Antoni Ribas, Georgina V Long, Ana Arance, Jean-Jacques Grob, Laurent Mortier, Adil Daud, Matteo S Carlino, Catriona McNeil, Michal Lotem, James Larkin, Paul Lorigan, Bart Neyns, Christian Blank, Teresa M Petrella, Omid Hamid, Honghong Zhou, Scot Ebbinghaus, Nageatte Ibrahim, Caroline Robert
BACKGROUND: Interim analyses of the phase 3 KEYNOTE-006 study showed superior overall and progression-free survival of pembrolizumab versus ipilimumab in patients with advanced melanoma. We present the final protocol-specified survival analysis. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we recruited patients from 87 academic institutions, hospitals, and cancer centres in 16 countries (Australia, Austria, Belgium, Canada, Chile, Colombia, France, Germany, Israel, Netherlands, New Zealand, Norway, Spain, Sweden, UK, and USA)...
August 16, 2017: Lancet
https://www.readbyqxmd.com/read/28822516/comparison-of-yoga-and-walking-exercise-on-cardiac-time-intervals-as-a-measure-of-cardiac-function-in-elderly-with-increased-pulse-pressure
#3
Satish Gurunathrao Patil, Shankargouda S Patil, Manjunatha R Aithala, Kusal Kanti Das
OBJECTIVE: Arterial aging along with increased blood pressure(BP) has become the major cardiovascular(CV) risk in elderly. The aim of the study was to compare the effects of yoga program and walking-exercise on cardiac function in elderly with increased pulse pressure (PP). METHODS: An open label, parallel-group randomized controlled study design was adopted. Elderly individuals aged ≥60 years with PP≥60mmHg were recruited for the study. Yoga (study) group (n=30) was assigned for yoga training and walking (exercise) group (n=30) for walking with loosening practices for one hour in the morning for 6days in a week for 3 months...
July 2017: Indian Heart Journal
https://www.readbyqxmd.com/read/28822073/isorhynchophylline-attenuates-mpp-induced-apoptosis-through-endoplasmic-reticulum-stress-and-mitochondria-dependent-pathways-in-pc12-cells-involvement-of-antioxidant-activity
#4
Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong
Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP(+)-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP(+)-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway...
August 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#5
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28821924/-89-zr-labeled-nivolumab-for-imaging-of-t-cell-infiltration-in-a-humanized-murine-model-of-lung-cancer
#6
Christopher G England, Dawei Jiang, Emily B Ehlerding, Brian T Rekoske, Paul A Ellison, Reinier Hernandez, Todd E Barnhart, Douglas G McNeel, Peng Huang, Weibo Cai
PURPOSE: Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes. METHODS: (89)Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer...
August 19, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28821883/synthesis-of-pincer-type-extractants-for-selective-extraction-of-palladium-from-pgms-an-improved-liquid-liquid-extraction-approach-to-current-refining-processes
#7
Muniyappan Rajiv Gandhi, Manabu Yamada, Kazutoshi Haga, Atsushi Shibayama
SCS pincer ligands 1-4 were synthesised, and their ability to extract Pd(II) from HCl and HNO3 media was studied. The Pd(II) extraction properties of 1-4 were compared with those of commercial extractants (DOS and LIX(®)84-I) in kerosene. 1 and 2 showed superior Pd(II) extractability (E% = 99.9) relative to DOS and LIX(®)84-I from 0.1-8.0 M HCl and to DOS from 0.1-8.0 M HNO3 and mixed HCl + HNO3 media. The Pd(II) extraction rate, acid durability, the most suitable organic/aqueous (O/A) phase ratio, and Pd(II) loading capacity of extractants 1, 2, and DOS were evaluated...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821831/targeted-inhibition-of-rage-in-substantia-nigra-of-rats-blocks-6-ohda-induced-dopaminergic-denervation
#8
Juciano Gasparotto, Camila Tiefensee Ribeiro, Rafael Calixto Bortolin, Nauana Somensi, Thallita Kelly Rabelo, Alice Kunzler, Natália Cabral Souza, Matheus Augusto de Bittencourt Pasquali, José Claudio Fonseca Moreira, Daniel Pens Gelain
The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821806/longitudinal-study-of-changes-in-%C3%AE-%C3%AE-t-cells-and-cd4-t-cells-upon-asymptomatic-malaria-infection-in-indonesian-children
#9
Sanne E de Jong, Vera E R Asscher, Linda J Wammes, Aprilianto E Wiria, Firdaus Hamid, Erliyani Sartono, Taniawati Supali, Hermelijn H Smits, Adrian J F Luty, Maria Yazdanbakhsh
Both γδ T cells and CD4(+) T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of γδ T cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. Infected children also had higher levels of Th1 and Th17 cells, lower levels of CD25(Hi) FOXP3(+) regulatory T cells (Tregs), but similar levels of Th2 cells as compared to uninfected children...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821503/anti-ctla4-and-anti-pd-1-act-on-distinct-t-cell-populations
#10
(no author information available yet)
Both anti-PD-1 and anti-CTLA4 target subpopulations of exhausted-like CD8(+) T cells.
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28821435/model-based-population-pk-pd-analysis-of-furosemide-for-bp-lowering-effect-a-comparative-study-in-primary-and-secondary-hypertension
#11
Mahendra Shukla, Moustafa M A Ibrahim, Moon Jain, Swati Jaiswal, Abhisheak Sharma, Kashif Hanif, Jawahar Lal
Though numerous reports have demonstrated multiple mechanisms by which furosemide can exert its anti-hypertensive response. However, lack of studies describing PK-PD relationship for furosemide featuring its anti-hypertensive property has limited its usage as a blood pressure (BP) lowering agent. Serum concentrations and mean arterial BP were monitored following 40 and 80mgkg(-1) multiple oral dose of furosemide in spontaneously hypertensive rats (SHR) and DOCA-salt induced hypertensive (DOCA-salt) rats. A simultaneous population PK-PD relationship using Emax model with effect compartment was developed to compare the anti-hypertensive efficacy of furosemide in these rat models...
August 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28821274/candidate-inflammatory-biomarkers-display-unique-relationships-with-alpha-synuclein-and-correlate-with-measures-of-disease-severity-in-subjects-with-parkinson-s-disease
#12
Lori N Eidson, George T Kannarkat, Christopher J Barnum, Jianjun Chang, Jaegwon Chung, Chelsea Caspell-Garcia, Peggy Taylor, Brit Mollenhauer, Michael G Schlossmacher, Larry Ereshefsky, Mark Yen, Catherine Kopil, Mark Frasier, Kenneth Marek, Vicki S Hertzberg, Malú G Tansey
BACKGROUND: Efforts to identify fluid biomarkers of Parkinson's disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28821192/could-the-pd-1-pathway-be-a-potential-target-for-treating-small-intestinal-adenocarcinoma
#13
Ramya Thota, Raul S Gonzalez, Jordan Berlin, Dana B Cardin, Chanjuan Shi
Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry. Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Tumors were immunohistochemically stained for CD3, CD4, CD8, CD20, PD-1, and programmed death ligand 1 (PD-L1) expression...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28821031/surface-deacetylated-chitin-nanofibers-reinforced-with-a-sulfobutyl-ether-%C3%AE-cyclodextrin-gel-loaded-with-prednisolone-as-potential-therapy-for-inflammatory-bowel-disease
#14
Ryo Tabuchi, Makoto Anraku, Daisuke Iohara, Takako Ishiguro, Shinsuke Ifuku, Tomone Nagae, Kaneto Uekama, Shoko Okazaki, Keizo Takeshita, Masaki Otagiri, Fumitoshi Hirayama
Surface-deacetylated chitin nanofibers (SDACNFs) reinforced with a sulfobutyl ether β-cyclodextrin (SBE-β-CD) (NFs-CDs) gel were developed to obtain a controlled release carrier of prednisolone (PD) for the treatment of colitis. PD was released slowly from the gel at both pH 1.2 and 6.8. The in vitro slow release of PD from the NFs-CDs gel was reflected in the in vivo absorption of the drug after oral administration to rats. These results suggest that a simple gel composed of a mixture of SDACNFs and SBE-β-CD has the potential for use in the controlled release of PD...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28820897/persistent-infection-due-to-a-small-colony-variant-of-burkholderia-pseudomallei-leads-to-pd-1-upregulation-on-circulating-immune-cells-and-mononuclear-infiltration-in-viscera-of-experimental-balb-c-mice
#15
Jia-Xiang See, Samudi Chandramathi, Mahmood Ameen Abdulla, Jamuna Vadivelu, Esaki M Shankar
BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28820444/a-novel-partial-discharge-localization-method-in-substation-based-on-a-wireless-uhf-sensor-array
#16
Zhen Li, Lingen Luo, Nan Zhou, Gehao Sheng, Xiuchen Jiang
Effective Partial Discharge (PD) localization can detect the insulation problems of the power equipment in a substation and improve the reliability of power systems. Typical Ultra-High Frequency (UHF) PD localization methods are mainly based on time difference information, which need a high sampling rate system. This paper proposes a novel PD localization method based on a received signal strength indicator (RSSI) fingerprint to quickly locate the power equipment with potential insulation defects. The proposed method consists of two stages...
August 18, 2017: Sensors
https://www.readbyqxmd.com/read/28820333/protease-dead-separase-inhibits-chromosome-segregation-and-rab-11-vesicle-trafficking
#17
Xiaofei Bai, Joshua N Bembenek
Separase cleaves cohesin to allow chromosome segregation. Separase also regulates cortical granule exocytosis and vesicle trafficking during cytokinesis, both of which involve RAB-11. We investigated whether separase regulates exocytosis through a proteolytic or non-proteolytic mechanism. In C. elegans, protease-dead separase (SEP-1(PD)::GFP) is dominant negative. Consistent with its role in cohesin cleavage, SEP-1(PD)::GFP causes chromosome segregation defects. As expected, partial depletion of cohesin rescues this defect, confirming that SEP-1(PD)::GFP acts through a substrate trapping mechanism...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820253/bioinorganic-chemistry-of-parkinson-s-disease-affinity-and-structural-features-of-cu-i-binding-to-the-full-length-%C3%AE-synuclein-protein
#18
Marco C Miotto, Mayra D Pavese, Liliana Quintanar, Markus Zweckstetter, Christian Griesinger, Claudio O Fernández
Alterations in the levels of copper in brain tissue and formation of α-synuclein (αS)-copper complexes might play a key role in the amyloid aggregation of αS and the onset of Parkinson's disease (PD). Recently, we demonstrated that formation of the high-affinity Cu(I) complex with the N-terminally acetylated form of the protein αS substantially increases and stabilizes local conformations with α-helical secondary structure and restricted motility. In this work, we performed a detailed NMR-based structural characterization of the Cu(I) complexes with the full-length acetylated form of its homologue β-synuclein (βS), which is colocalized with αS in vivo and can bind copper ions...
August 18, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28820242/expanding-the-scope-of-ligand-substitution-from-m-s2c2ph2-m-ni-2-pd-2-pt-2-to-afford-new-heteroleptic-dithiolene-complexes
#19
Antony Obanda, Kristina Martinez, Russell H Schmehl, Joel T Mague, Igor V Rubtsov, Samantha N MacMillan, Kyle M Lancaster, Stephen Sproules, James P Donahue
The scope of direct substitution of the dithiolene ligand from [M(S2C2Ph2)2] [M = Ni(2+) (1), Pd(2+) (2), Pt(2+) (3)] to produce heteroleptic species [M(S2C2Ph2)2Ln] (n = 1, 2) has been broadened to include isonitriles and dithiooxamides in addition to phosphines and diimines. Collective observations regarding ligands that cleanly produce [M(S2C2Ph2)Ln], do not react at all, or lead to ill-defined decomposition identify soft σ donors as the ligand type capable of dithiolene substitution. Substitution of MeNC from [Ni(S2C2Ph2)(CNMe)2] by L provides access to a variety of heteroleptic dithiolene complexes not accessible from 1...
August 18, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28820159/surgical-treatment-of-superior-oblique-palsy-predictors-of-outcome
#20
Pilar Merino Sanz, José Escribano, Pilar Gómez de Liaño, Rubén Yela
PURPOSE: The purpose of this study was to evaluate the incidence and outcome of surgically treated superior oblique palsy (SOP) and the factors involved in its resolution. METHODS: We performed a retrospective study of 76 patients who underwent surgery for SOP. We recorded data from the physical examination and the number and type of procedures performed. Favorable outcome was defined as resolution of or improvement in torticollis (≤5°) and diplopia in primary position (PP) and downgaze or as vertical deviation (VD) <5 prism diopters (pd) in PP and 10 pd in the oblique diagnostic position...
August 2017: Indian Journal of Ophthalmology
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