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https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#1
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346778/diverse-brain-myeloid-expression-profiles-reveal-distinct-microglial-activation-states-and-aspects-of-alzheimer-s-disease-not-evident-in-mouse-models
#2
Brad A Friedman, Karpagam Srinivasan, Gai Ayalon, William J Meilandt, Han Lin, Melanie A Huntley, Yi Cao, Seung-Hye Lee, Patrick C G Haddick, Hai Ngu, Zora Modrusan, Jessica L Larson, Joshua S Kaminker, Marcel P van der Brug, David V Hansen
Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346777/prrt2-regulates-synaptic-fusion-by-directly-modulating-snare-complex-assembly
#3
Jeff Coleman, Ouardane Jouannot, Sathish K Ramakrishnan, Maria N Zanetti, Jing Wang, Vincenzo Salpietro, Henry Houlden, James E Rothman, Shyam S Krishnakumar
Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the pre-synaptic terminals and is believed to regulate neurotransmitter release. However, the mechanism of action is unclear. Here, we use reconstituted single vesicle and bulk fusion assays, combined with live cell imaging of single exocytotic events in PC12 cells and biophysical analysis, to delineate the physiological role of PRRT2. We report that PRRT2 selectively blocks the trans SNARE complex assembly and thus negatively regulates synaptic vesicle priming...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346760/single-cell-transcriptional-profiling-reveals-cellular-diversity-and-intercommunication-in-the-mouse-heart
#4
Daniel A Skelly, Galen T Squiers, Micheal A McLellan, Mohan T Bolisetty, Paul Robson, Nadia A Rosenthal, Alexander R Pinto
Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition and highlighted important functional roles for non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-seq)...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346505/clustering-single-cells-a-review-of-approaches-on-high-and-low-depth-single-cell-rna-seq-data
#5
Vilas Menon
No abstract text is available yet for this article.
January 16, 2018: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29346495/long-term-temporal-changes-in-structure-and-function-of-rat-visual-system-after-blast-exposure
#6
Daniel F Shedd, Nikolaus A Benko, Justin Jones, Brian E Zaugg, Robert L Peiffer, Brittany Coats
Purpose: We identify long-term ocular sequelae subsequent to experimental blast exposure. Methods: Male Long-Evans rats were exposed to 230 kPa side-on primary blast overpressure using a compressed air driven shock tube. Visual system function and structure were assessed for 8 weeks after exposure using optokinetic nystagmus and optical coherence tomography. Vitreous protein expression and histology (TUNEL, H&E) were performed at 1 day and 1, 4, and 8 weeks. IOP was recorded bilaterally during blast in a subset of animals...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29346494/novel-myopia-genes-and-pathways-identified-from-syndromic-forms-of-myopia
#7
D Ian Flitcroft, James Loughman, Christine F Wildsoet, Cathy Williams, Jeremy A Guggenheim
Purpose: To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. Methods: Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29346449/within-host-selection-for-faster-replicating-bacterial-symbionts
#8
Ewa Chrostek, Luis Teixeira
Wolbachia is a widespread, intracellular symbiont of arthropods, able to induce reproductive distortions and antiviral protection in insects. Wolbachia can also be pathogenic, as is the case with wMelPop, a virulent variant of the endosymbiont of Drosophila melanogaster. An extensive genomic amplification of the 20kb region encompassing eight Wolbachia genes, called Octomom, is responsible for wMelPop virulence. The Octomom copy number in wMelPop can be highly variable between individual D. melanogaster flies, even when comparing siblings arising from a single female...
2018: PloS One
https://www.readbyqxmd.com/read/29346439/interspecies-diversity-of-chloride-channel-regulators-calcium-activated-3-genes
#9
Lars Mundhenk, Nancy A Erickson, Nikolai Klymiuk, Achim D Gruber
Members of the chloride channel regulators, calcium-activated (CLCA) family, have been implicated in diverse biomedical conditions, including chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, the activation of macrophages, and the growth and metastatic spread of tumor cells. Several observations, however, could not be repeated across species boundaries and increasing evidence suggests that select CLCA genes are particularly prone to dynamic species-specific evolvements...
2018: PloS One
https://www.readbyqxmd.com/read/29346421/the-absence-of-specific-yeast-heat-shock-proteins-leads-to-abnormal-aggregation-and-compromised-autophagic-clearance-of-mutant-huntingtin-proteins
#10
Ryan Higgins, Marie-Helene Kabbaj, Alexa Hatcher, Yanchang Wang
The functionality of a protein depends on its correct folding, but newly synthesized proteins are susceptible to aberrant folding and aggregation. Heat shock proteins (HSPs) function as molecular chaperones that aid in protein folding and the degradation of misfolded proteins. Trinucleotide (CAG) repeat expansion in the Huntingtin gene (HTT) results in the expression of misfolded Huntingtin protein (Htt), which contributes to the development of Huntington's disease. We previously found that the degradation of mutated Htt with polyQ expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy...
2018: PloS One
https://www.readbyqxmd.com/read/29346409/prediction-of-absolute-risk-of-acute-graft-versus-host-disease-following-hematopoietic-cell-transplantation
#11
Catherine Lee, Sebastien Haneuse, Hai-Lin Wang, Sherri Rose, Stephen R Spellman, Michael Verneris, Katharine C Hsu, Katharina Fleischhauer, Stephanie J Lee, Reza Abdi
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for a variety of hematologic malignancies and disorders. Unfortunately, acute graft-versus-host disease (GVHD) is a frequent complication of HCT. While substantial research has identified clinical, genetic and proteomic risk factors for acute GVHD, few studies have sought to develop risk prediction tools that quantify absolute risk. Such tools would be useful for: optimizing donor selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring strategies; and, recruitment of patients into clinical trials...
2018: PloS One
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#12
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29346131/toxicological-profile-and-safety-pharmacology-of-a-single-dose-of-fibroblast-activation-protein-%C3%AE-based-doxorubicin-prodrug-in-vitro-and-in-vivo-evaluation
#13
Sichao Huang, Yuchen Zhang, Jinsong Zhong, Ying Pan, Shaohui Cai, Jun Xu
Fibroblast activation protein-α (FAPα) is a promising tumor-associated target expressed by reactive stromal fibroblasts in tumor tissue. FAPα has a postprolyl peptidase activity and can specifically cleave N-terminal benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC. Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly limited by toxic adverse effects owing to poor tumor selectivity. Based on these facts, we previously designed a FAPα-targeting prodrug of doxorubicin (FTPD) which can be selectively hydrolyzed by FAPα...
January 17, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29346103/wavedec-a-wavelet-approach-to-identify-both-shared-and-individual-patterns-of-copy-number-variations
#14
Hongmin Cai, Peihua Chen, Jiazhou Chen, Jiulun Cai, Yan Song, Guoqiang Han
Copy-number variations (CNVs) are associated with complex diseases and particular tumor types. Array-based comparative genomic hybridization (aCGH) is a common approach for the detection of CNVs. Traditional CNV detection methods for multiple aCGH samples mainly use batch samples to find common variations, not accounting for the individual characteristics of each sample. Accurately differentiating both the commonly shared and the individual CNV patterns is pivotal to identify cell populations, or to distinguish cell growth (as in cancer) from invasion of new cells...
February 2018: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/29346077/three-dimensional-graphene-biointerface-with-extremely-high-sensitivity-to-single-cancer-cell-monitoring
#15
Xiahua Wang, Aiping Liu, Yun Xing, Hongwei Duan, Weizhong Xu, Qi Zhou, Huaping Wu, Cen Chen, Benyong Chen
We developed a three-dimensional biointerface of graphene-based electrical impedance sensor for metastatic cancer diagnosis at single-cell resolution. Compared with traditional impedance sensor with two-dimensional interface, the graphene biointerface mimiced the topography and somatotype features of cancer cells, achieving more comprehensive and thorough single cell signals in the three-dimensional space. At the nodes of physiological behavior change of single cell, namely cell capture, adhesion, migration and proliferation, the collected electrical signals from graphene biointerface were about two times stronger than those from the two-dimensional gold interface due to the substantial increase in contact area and significant improvement of topographical interaction between cells and graphene electrode...
January 9, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29346028/biophysics-model-of-heavy-ion-degradation-of-neuron-morphology-in-mouse-hippocampal-granular-cell-layer-neurons
#16
Murat Alp, Francis A Cucinotta
Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors...
January 18, 2018: Radiation Research
https://www.readbyqxmd.com/read/29345990/imaging-mrna-in-vivo-from-birth-to-death
#17
Evelina Tutucci, Nathan M Livingston, Robert H Singer, Bin Wu
RNA is the fundamental information transfer system in the cell. The ability to follow single messenger RNAs (mRNAs) from transcription to degradation with fluorescent probes gives quantitative information about how the information is transferred fromDNAto proteins. This review focuses on the latest technological developments in the field of single-mRNA detection and their usage to study gene expression in both fixed and live cells. By describing the application of these imaging tools, we follow the journey of mRNA from transcription to decay in single cells, with single-molecule resolution...
January 18, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29345922/efficient-fusion-at-neutral-ph-by-human-immunodeficiency-virus-gp41-trimers-containing-the-fusion-peptide-and-transmembrane-domain
#18
Shuang Liang, Punsisi Ratnayake, Craig Keinath, Lihui Jia, Robert Wolfe, Ahinsa Ranaweera, David P Weliky
Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). The virion initially has non-covalent complexes between three gp41 ectodomains and three gp120 proteins...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345755/expression-of-hepatic-progenitor-cell-markers-in-acute-cellular-rejection-of-liver-allografts-an-immunohistochemical-study
#19
Regina Cheuk-Lam Lo, Kristy Kwan-Shuen Chan, Carmen Oi-Ning Leung, Irene Oi-Lin Ng
BACKGROUND: Hepatic progenitor cells (HPC) are induced following liver injury to facilitate regeneration. Acute cellular rejection (ACR) is a common complication after liver transplantation as a result of immune-mediated liver injury. In this study we characterized HPC phenotype in liver allograft biopsy with ACR. We also explored the correlation between expression HPC immunophenotype and clinicopathological parameters. METHODS: Forty-four liver allograft biopsies performed between 2008-2016 in a single center with histologically proven ACR were examined for immunohistochemical expression of HPC markers CK19 and Sox9...
January 18, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29345751/first-evidence-of-freezing-tolerance-in-a-resurrection-plant-insights-into-molecular-mobility-and-zeaxanthin-synthesis-in-the-dark
#20
Beatriz Fernández-Marín, Gilbert Neuner, Edith Kuprian, Jose Manuel Laza, J I José Ignacio García-Plazaola, Amy Verhoeven
The photoprotective mechanisms of desiccation tolerance and freezing tolerance and their relation to molecular mobility (cell vitrification) were assessed in a single model: the exceptional subalpine and resurrection plant Ramonda myconi. Dehydrated leaves showed a drop in Fv /Fm accompanied by synthesis of zeaxanthin (Z), even in the dark, which was limited by cell vitrification after complete desiccation. The recovery of Fv /Fm after a severe drying treatment (7 d at 50% RH) confirmed the tolerance of R. myconi leaves to desiccation...
January 18, 2018: Physiologia Plantarum
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