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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/28423535/overall-survival-with-crizotinib-and-next-generation-alk-inhibitors-in-alk-positive-non-small-cell-lung-cancer-ifct-1302-clinalk-a-french-nationwide-cohort-retrospective-study
#2
Michaël Duruisseaux, Benjamin Besse, Jacques Cadranel, Maurice Pérol, Bertrand Mennecier, Laurence Bigay-Game, Renaud Descourt, Eric Dansin, Clarisse Audigier-Valette, Lionel Moreau, José Hureaux, Remi Veillon, Josiane Otto, Anne Madroszyk-Flandin, Alexis Cortot, François Guichard, Pascaline Boudou-Rouquette, Alexandra Langlais, Pascale Missy, Franck Morin, Denis Moro-Sibilot
Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410288/the-utility-of-the-combination-of-a-spect-study-with-123i-fp-cit-of-dopamine-transporters-and-123i-mibg-myocardial-scintigraphy-in-differentiating-parkinson-disease-from-other-degenerative-parkinsonian-syndromes
#3
Naoto Uyama, Hideki Otsuka, Takayoshi Shinya, Yoichi Otomi, Masafumi Harada, Wataru Sako, Yuishin Izumi, Ryuji Kaji, Yuya Watanabe, Satoru Takashi, Yamato Kunikane
OBJECTIVE: Molecular imaging of nigrostriatal dopamine transporters (DAT) and sympathetic cardiac innervation with single-photon emission computed tomography (SPECT) are useful tools for differentiating idiopathic Parkinson disease (PD) from other degenerative parkinsonian syndromes (non-PD). Nevertheless, these modalities are often insufficient for achieving a definite diagnosis. The aims of this study were to evaluate the diagnostic accuracy of the combination of these tools. MATERIALS AND METHODS: The SPECT radiotracers [I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (FP-CIT) and meta-[I]-iodobenzylguanidine (MIBG) were used to research presynaptic dopaminergic projections (DAT SPECT) and myocardial adrenergic innervation (MIBG scintigraphy), respectively...
April 13, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28397821/t-cell-invigoration-to-tumour-burden-ratio-associated-with-anti-pd-1-response
#4
Alexander C Huang, Michael A Postow, Robert J Orlowski, Rosemarie Mick, Bertram Bengsch, Sasikanth Manne, Wei Xu, Shannon Harmon, Josephine R Giles, Brandon Wenz, Matthew Adamow, Deborah Kuk, Katherine S Panageas, Cristina Carrera, Phillip Wong, Felix Quagliarello, Bradley Wubbenhorst, Kurt D'Andrea, Kristen E Pauken, Ramin S Herati, Ryan P Staupe, Jason M Schenkel, Suzanne McGettigan, Shawn Kothari, Sangeeth M George, Robert H Vonderheide, Ravi K Amaravadi, Giorgos C Karakousis, Lynn M Schuchter, Xiaowei Xu, Katherine L Nathanson, Jedd D Wolchok, Tara C Gangadhar, E John Wherry
Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. Pre-existing T-cell infiltration and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after treatment with the PD-1-targeting antibody pembrolizumab and identify pharmacodynamic changes in circulating exhausted-phenotype CD8 T cells (Tex cells)...
April 10, 2017: Nature
https://www.readbyqxmd.com/read/28396287/ability-of-palatable-food-consumption-to-buffer-against-the-short-and-long-term-behavioral-consequences-of-social-defeat-exposure-during-juvenility-in-rats
#5
J C MacKay, P Kent, J S James, C Cayer, Z Merali
In adult rats, access to a palatable diet can buffer against the effects of stressors. Approximately 10% of all adolescents are repeatedly victimized by their peers raising the possibility that palatable food consumption may be relevant to this developmental window. This study assessed the long-term impact of juvenile social defeat exposure on anxiety and depressive-like behavior and whether daily limited access to a palatable diet moderated these behavioral consequences. We also investigated the impact of the palatable diet on behavior during the defeat sessions...
April 7, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28393348/housing-accessibility-problems-for-people-with-parkinson-s-disease
#6
B Slaug, S Iwarsson, J A Ayala, M H Nilsson
OBJECTIVES: Promoting accessible housing for all citizens is high on the political agenda. Knowledge is, however, limited regarding housing accessibility problems for people with Parkinson's disease (PD). The objectives were to investigate housing accessibility problems among people with PD at different stages of disease severity and to analyze the potential impact of improved functional ability on accessibility problems. MATERIALS AND METHODS: The study included 253 participants with PD (61% men; mean age 70 years)...
April 9, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28391672/endoscopic-ultrasound-guided-pancreatic-duct-intervention
#7
REVIEW
Yuto Shimamura, Jeffrey Mosko, Christopher Teshima, Gary R May
Endoscopic ultrasound-guided pancreatic duct intervention (EUS-PDI) is an emerging endoscopic approach allowing access and intervention to the pancreatic duct (PD) for patients with failed endoscopic retrograde pancreatography (ERP) or patients with surgically altered anatomy. As opposed to biliary drainage for which percutaneous drainage is an alternative following failed endoscopic retrograde cholangiopancreatography (ERCP), the treatment options after failed ERP are very limited. Therefore, endoscopic ultrasound (EUS)-guided access to the PD and options for subsequent drainage may play an important role as an alternative to surgical intervention...
March 2017: Clinical Endoscopy
https://www.readbyqxmd.com/read/28388939/auto-detection-and-segmentation-of-daily-living-activities-during-a-timed-up-and-go-task-in-people-with-parkinson-s-disease-using-multiple-inertial-sensors
#8
Hung Nguyen, Karina Lebel, Patrick Boissy, Sarah Bogard, Etienne Goubault, Christian Duval
BACKGROUND: Wearable sensors have the potential to provide clinicians with access to motor performance of people with movement disorder as they undergo intervention. However, sensor data often have to be manually classified and segmented before they can be processed into clinical metrics. This process can be time consuming. We recently proposed detection and segmentation algorithms based on peak detection using Inertial Measurement Units (IMUs) to automatically identify and isolate common activities during daily living such as standing up, walking, turning, and sitting down...
April 7, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28385514/nr4a2-genetic-variation-and-parkinson-s-disease-evidence-from-a-systematic-review-and-meta-analysis
#9
Hongmei Liu, Hongbo Liu, Ting Li, Jiayi Cui, Yingmei Fu, Juanjuan Ren, Xiujia Sun, Ping Jiang, Shunying Yu, Chunbo Li
INTRODUCTION: the homo sapiens nuclear receptor subfamily 4, group A (NR4A2) genetic variation has been implicated as a risk factor for Parkinson's disease (PD). Nevertheless, the results are inconclusive. We conducted a comprehensive systematic review and meta-analysis to quantify the impact of NR4A2 variation on the risk of PD. METHODS: all eligible case-control studies published up to June 2016 by searching Pubmed, OVID, EBSCO, PsycINFO, ISI Web of Knowledge, Chinese Biomedical Literature Database and China Academic Journals Database were identified...
April 4, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28375643/pimavanserin
#10
Kevin M Bozymski, Denise K Lowe, Kiersten M Pasternak, Travis L Gatesman, Ericka L Crouse
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP). DATA SOURCES: A comprehensive PubMed search (1966 to January 2017) was conducted using the search terms Parkinson's disease psychosis, hallucinations, delusions, pimavanserin, and ACP-103. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling and website, and Clinicaltrials...
February 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28370917/palladium-catalyzed-fluorosulfonylvinylation-of-organic-iodides
#11
Gao-Feng Zha, Qinheng Zheng, Jing Leng, Peng Wu, Hua-Li Qin, K Barry Sharpless
A palladium-catalyzed fluorosulfonylvinylation reaction of organic iodides is described. Catalytic Pd(OAc)2 with a stoichiometric amount of silver(I) trifluoroacetate enables the coupling process between either an (hetero)aryl or alkenyl iodide with ethenesulfonyl fluoride (ESF). The method is demonstrated in the successful syntheses of eighty-eight otherwise difficult to access compounds, in up to 99 % yields, including the unprecedented 2-heteroarylethenesulfonyl fluorides and 1,3-dienylsulfonyl fluorides...
March 29, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28367553/pd-cu-catalyzed-dual-c-h-bond-carbonylation-towards-the-synthesis-of-fluorazones
#12
Fan Liao, Renyi Shi, Yuchen Sha, Jianhui Xia, Weilin Liao, Aiwen Lei
Pd/Cu catalyzed oxidative dual C-H bond activation/carbonylation still remains a great challenge due to the generation of by-products via C-C bond formation. Herein we developed a straightforward Pd/Cu-catalyzed oxidative dual C-H bond carbonylation process to access biologically and pharmaceutically important fluorazones from easily available N-aryl pyrroles and CO. A wide range of functional groups were well tolerated in this transformation, and O2 could be utilized as the only terminal oxidant to promote the oxidative carbonylation process...
April 3, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28361153/optimized-synthesis-of-%C3%AF-extended-squaraine-dyes-relevant-to-organic-electronics-by-direct-hetero-arylation-and-sonogashira-coupling-reactions
#13
Abby-Jo Payne, Gregory C Welch
This study reports on the synthesis and characterization of four molecular π-extended squaraine compounds relevant to the field of organic electronics. The compounds each consist of a bis-indole squaraine core end-capped with indoloquinoxaline units employing three different bridging units, namely thiophene, thiazole, and acetylene. Compound 10 bears a thiophene bridge, 11 consists of a thiophene bridge and fluorinated indoloquinoxaline terminal units, and compounds 12 and 13 are bridged by thiazole and acetylene, respectively...
April 11, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28360370/barriers-to-increasing-use-of-peritoneal-dialysis-in-bangladesh-a-survey-of-patients-and-providers
#14
Dipal Savla, Sweety Ahmed, Karen Yeates, Anna Matthew, Shuchi Anand
Despite a lower requirement for technology and equipment than hemodialysis (HD), peritoneal dialysis (PD) is an underutilized modality in low- and middle-income countries (LMICs). Bangladesh has the lowest use of PD in the world (fewer than 2% of prevalent patients). We evaluated nephrologists' attitudes toward PD and examined differences between patients on HD and PD in Dhaka. We asked nephrologists to fill out an English-language questionnaire. Using convenience sampling but targeting both public and private hospitals in Dhaka, we asked trained nurses to administer a Bangla-language questionnaire to patients on HD (n = 116) and PD (n = 41)...
March 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28360219/a-new-mechanism-of-voltage-dependent-gating-exposed-by-kv10-1-channels-interrupted-between-voltage-sensor-and-pore
#15
Adam P Tomczak, Jorge Fernández-Trillo, Shashank Bharill, Ferenc Papp, Gyorgy Panyi, Walter Stühmer, Ehud Y Isacoff, Luis A Pardo
Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4-S5 linker). However, our recent work on channels disrupted in the S4-S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of KV10.1 revealed that the S4-S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model...
March 30, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28346788/three-step-catalytic-asymmetric-total-syntheses-of-13-methyltetrahydroprotoberberine-alkaloids
#16
Shiqiang Zhou, Rongbiao Tong
(S,R)-N-PINAP was identified to be the chiral ligand for highly enantioselective CuI-catalyzed reaction of tetrahydroisoquinolines (THIQs), alkynes, and 2-bromobenzaldehyde derivatives. This enables us to accomplish the first asymmetric total synthesis of 12 natural 13-methyltetrahydroprotoberberine (13-MeTHPB) alkaloids in only three catalytic steps with 47-64% overall yields. In addition, the Pd-catalyzed reductive Heck cyclization was successfully extended to three Pd-catalyzed domino reactions (Heck/Suzuki, Heck/Sonogashira, and Heck/Heck), which greatly expands the synthetic utility of this catalytic strategy and allows expeditious access to 13-substituted tetrahydroprotoberberines for further bioactivity evaluation...
April 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28297057/dialysis-access-issues-related-to-conversion-from-peritoneal-dialysis-to-hemodialysis-and-vice-versa
#17
Maurizio Gallieni, Antonino Giordano, Anna Ricchiuto, Davide Gobatti, Maurizio Cariati
ABSTRACTHemodialysis (HD) and peritoneal dialysis (PD) represent two complementary modalities of renal replacement therapy (RRT) for end-stage renal disease patients. Conversion between the two modalities is frequent and more likely to happen from PD to HD. Every year, 10% of PD patients convert to HD, suggesting the need for recommendations on how to proceed with the creation of a vascular access in these patients. Criteria for selecting patients who would likely fail PD, and therefore take advantage of a backup access, are undefined...
March 6, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/28290702/palladium-catalyzed-double-allylation-of-sugar-imines-by-employing-tamaru-kimura-s-protocol-access-to-unnatural-iminosugars
#18
Annavareddi Naresh, Kanakaraju Marumudi, A C Kunwar, Batchu Venkateswara Rao
Conversion of vinyl pyranosylamine and vinyl furanosylamines to 2,6- and 2,5-disubstituted pyrrolidine and piperidine iminosugars, respectively, in one pot was developed using Kimura and Tamaru's procedure, where a Pd salt in the presence of Et2Zn was used for the domino reaction. In this procedure, double allylation, which involves nucleophilic allylation-heterocyclization, took place to give desired nitrogen heterocycles. This strategy was further elaborated to synthesize some unnatural deoxycalystegines, hydroxylated pyrrolidines, piperidines, and indolizidine analogues...
April 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28290578/pd-cu-catalyzed-tandem-head-to-tail-dimerization-cycloisomerization-of-terminal-ynamides-for-the-synthesis-of-5-vinyloxazolones
#19
Luning Tang, Hai Huang, Yang Xi, Guangke He, Hongjun Zhu
An attractive and novel methodology involving Pd/Cu-catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 3,5-disubstituted oxazolones was developed. Under Pd(PPh3)2Cl2/CuI cooperative catalyzed reaction conditions, it provided efficient access to 5-vinyloxazolones with exceptional functional group tolerance and good chemoselectivity. The control experiments demonstrated that Pd(PPh3)2Cl2 serves a key role in the dimerization of terminal ynamides and shows low catalytic activity in the intramolecular cyclization...
March 14, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28289736/palladium-catalyzed-regioselective-c-h-fluoroalkylation-of-indoles-at-the-c4-position
#20
Arun Jyoti Borah, Zhuangzhi Shi
An exclusive catalytic C4-selective fluoroalkylation of indoles with highly active (1H, 1H-perfluoroalkyl)mesityliodonium triflate has been described. The key to its high regioselectivity is the appropriate choice of an easily accessible, cheap and removable directing group at the C3 position in the presence of a Pd(OAc)2 catalyst. Besides indole fluoroalkylation, the application of this strategy in other heteroarenes such as benzo[b]thiophene is also described.
March 14, 2017: Chemical Communications: Chem Comm
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