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https://www.readbyqxmd.com/read/28921918/proteomic-response-of-human-umbilical-vein-endothelial-cells-to-histamine-stimulation
#1
Pelin Esma Emirbayer, Ankit Sinha, Vladimir Ignatchenko, Stefanie Hoyer, Jan Dörrie, Niels Schaft, Monika Pischetsrieder, Thomas Kislinger
The histamine receptors (HRs) represent a subclass of G protein-coupled receptors (GPCRs) and comprise four subtypes. Due to their numerous physiological and pathological effects, HRs are popular drug targets for the treatment of allergic reactions or the regulation of gastric acid secretion. Hence, an understanding of the functional selectivity of HR ligands has gained importance. These ligands can bind to specific GPCRs and selectively activate defined pathways. Supporting the activation of a therapeutically necessary pathway without the activation of other signaling cascades can result in drugs with more specific activity and fewer side effects...
September 18, 2017: Proteomics
https://www.readbyqxmd.com/read/28921872/first-line-therapy-with-dacomitinib-an-orally-available-pan-her-tyrosine-kinase-inhibitor-for-locally-advanced-or-metastatic-penile-squamous-cell-carcinoma-results-of-an-open-label-single-arm-single-center-phase-2-study
#2
A Necchi, S Lo Vullo, F Perrone, D Raggi, P Giannatempo, G Calareso, N Nicolai, L Piva, D Biasoni, M Catanzaro, T Torelli, S Stagni, E Togliardi, M Colecchia, A Busico, A Gloghini, A Testi, L Mariani, R Salvioni
OBJECTIVE: To harness the frontline therapy in advanced penile squamous cell carcinoma (PSCC), for which chemotherapy exerts moderate activity but poor efficacy. Dacomitinib is an irreversible, pan-epidermal growth factor receptor (HER) inhibitor. PATIENTS AND METHODS: In a phase 2 study (NCT01728233), patients received dacomitinib 45 mg/day, orally, continuously. Inclusion criteria were SCC histology, clinical stage N2-3 or M1 (TNM 2009), and no prior chemotherapy administration...
September 16, 2017: BJU International
https://www.readbyqxmd.com/read/28920441/new-insight-of-common-regulatory-pathways-in-human-trabecular-meshwork-cells-in-response-to-dexamethasone-and-prednisolone-using-an-integrated-quantitative-proteomics-swath-and-mrm-hr-mass-spectrometry
#3
Sze Wan Shan, Chi Wai Do, Thomas Chuen Lam, Ricky Pak Wing Kong, King Kit Li, Ka Man Chun, William Daniel Stamer, Chi Ho To
The molecular pathophysiology of corticosteroid-induced ocular hypertension (CIH) is not well understood. To determine the biological mechanisms of CIH, this study investigated protein expression profiles of human trabecular meshwork (hTM) cells in response to dexamethasone and prednisolone treatment. Both discovery-based Sequential Windowed data independent Acquisition of the Total High-resolution mass spectra (SWATH(TM)-MS) and targeted based high resolution multiple reaction monitoring (MRM-HR) confirmation were applied using a hybrid quadrupole-time-of-flight mass spectrometer...
September 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28919768/ictal-heart-rate-changes-and-the-effects-of-vagus-nerve-stimulation-for-patients-with-refractory-epilepsy
#4
Wei Chen, Fan-Gang Meng
Vagus nerve stimulation (VNS) shows long-term efficiency worldwide in most pharmacoresistant patients with epilepsy; however, there are still a small number of patients who are non-responders to VNS therapy. It has been shown that VNS treatment outcomes for drug-resistant epilepsy may be predicted by preoperative heart-rate variability measurements and that patients with epilepsy with ictal tachycardia (IT) during seizures have good responses to VNS. However, few studies have reported the efficacy of VNS in patients with epilepsy with ictal bradycardia (IB) or normal heart rate (HR), and none have explored the possible mechanisms of VNS efficacy based on different HR types...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28915673/prognositic-value-of-cd73-adenosinergic-pathway-in-solid-tumor-a-meta-analysis-and-systematic-review
#5
Rong Wang, Yingying Zhang, Xia Lin, Yalin Gao, Ying Zhu
CD73 is a glycosylphosphatidylinositol (GPI) anchored cell surface protein that is encoded by NT5E gene, plays multiple roles in tumor processes. Previous studies have presented a potential value of CD73 served as a detectable biomarker for prognosis of several solid tumors, but the results were more controversially. A comprehensive meta-analysis was conducted to precisely evaluate the prognostic role of CD73 in solid tumors. The included studies were searched in PubMed, Web of Science and EBSCO from Jan 1990 to Jan 2016...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914798/genome-instability-and-%C3%AE-h2ax
#6
REVIEW
Anastasios Georgoulis, Constantinos E Vorgias, George P Chrousos, Emmy P Rogakou
γH2AX has emerged in the last 20 years as a central player in the DDR (DNA damage response), with specificity for DSBs (double-strand breaks). Upon the generation of DSBs, γ-phosphorylation extends along megabase-long domains in chromatin, both sides of the damage. The significance of this mechanism is of great importance; it depicts a biological amplification mechanism where one DSB induces the γ-phosphorylation of thousands of H2AX molecules along megabaselong domains of chromatin, that are adjusted to the sites of DSBs...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28914166/repeated-iron-soot-exposure-and-nose-to-brain-transport-of-inhaled-ultrafine-particles
#7
Laurie E Hopkins, Emilia A Laing, Janice L Peake, Dale Uyeminami, Savannah M Mack, Xueting Li, Suzette Smiley-Jewell, Kent E Pinkerton
Particulate exposure has been implicated in the development of a number of neurological maladies such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, and idiopathic Parkinson's disease. Only a few studies have focused on the olfactory pathway as a portal through which combustion-generated particles may enter the brain. The primary objective of this study was to define the deposition, uptake, and transport of inhaled ultrafine iron-soot particles in the nasal cavities of mice to determine whether combustion-generated nanoparticles reach the olfactory bulb via the olfactory epithelium and nerve fascicles...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28912341/the-role-of-blm-helicase-in-homologous-recombination-gene-conversion-tract-length-and-recombination-between-diverged-sequences-in-drosophila
#8
Henry A Ertl, Daniel P Russo, Noori Srivastava, Joseph T Brooks, Thu N Dao, Jeannine R LaRocque
DNA double-strand breaks (DSBs) are a particularly deleterious class of DNA damage that threatens genome integrity. DSBs are repaired by three pathways: non-homologous end joining (NHEJ), homologous recombination (HR), and single-strand annealing (SSA). Drosophila melanogaster Blm (DmBlm) is the ortholog of Saccharomyces cerevisiae SGS1 and human BLM, and has been shown to suppress crossovers in mitotic cells and repair mitotic DNA gaps via HR. To further elucidate the role of DmBlm in repair of a simple DSB, and in particular recombination mechanisms, we utilized the DR-white and DR-white...
September 14, 2017: Genetics
https://www.readbyqxmd.com/read/28912125/blm-helicase-regulates-dna-repair-by-counteracting-rad51-loading-at-dna-double-strand-break-sites
#9
Dharm S Patel, Sarah M Misenko, Joonyoung Her, Samuel F Bunting
The BLM gene product, BLM, is a RECQ helicase that is involved in DNA replication and repair of DNA double-strand breaks by the homologous recombination (HR) pathway. During HR, BLM has both pro- and anti-recombinogenic activities, either of which may contribute to maintenance of genomic integrity. We find that in cells expressing a mutant version of BRCA1, an essential HR factor, ablation of BLM rescues genomic integrity and cell survival in the presence of DNA double-strand breaks. Improved genomic integrity in these cells is linked to a substantial increase in the stability of RAD51 at DNA double-strand break sites and in the overall efficiency of HR...
September 14, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28900495/differentially-expressed-lncrnas-in-gastric-cancer-patients-a-potential-biomarker-for-gastric-cancer-prognosis
#10
Xianglong Tian, Xiaoqiang Zhu, Tingting Yan, Chenyang Yu, Chaoqin Shen, Jie Hong, Haoyan Chen, Jing-Yuan Fang
Current studies indicate that long non-coding RNAs (lncRNAs) are frequently aberrantly expressed in cancers and implicated with prognosis in gastric cancer (GC). We intended to generate a multi-lncRNA signature to improve prognostic prediction of GC. By analyzing ten paired GC and adjacent normal mucosa tissues, 339 differentially expressed lncRNAs were identified as the candidate prognostic biomarkers in GC. Then we used LASSO Cox regression method to build a 12-lncRNA signature and validated it in another independent GEO dataset...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28900274/characterization-and-identification-of-a-woody-lesion-mimic-mutant-lmd-showing-defence-response-and-resistance-to-alternaria-alternate-in-birch
#11
Ranhong Li, Su Chen, Guifeng Liu, Rui Han, Jing Jiang
Lesion mimic mutants (LMM) usually show spontaneous cell death and enhanced defence responses similar to hypersensitive response (HR) in plants. Many LMM have been reported in rice, wheat, maize, barley, Arabidopsis, etc., but little was reported in xylophyta. BpGH3.5 is an early auxin-response factor which regulates root elongation in birch. Here, we found a T-DNA insertion mutant in a BpGH3.5 transgenic line named lmd showing typical LMM characters and early leaf senescence in Betula platyphylla × B...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900021/another-brick-in-the-wall-a-rhamnan-polysaccharide-trapped-inside-peptidoglycan-of-lactococcus-lactis
#12
Irina Sadovskaya, Evgeny Vinogradov, Pascal Courtin, Julija Armalyte, Mickael Meyrand, Efstathios Giaouris, Simon Palussière, Sylviane Furlan, Christine Péchoux, Stuart Ainsworth, Jennifer Mahony, Douwe van Sinderen, Saulius Kulakauskas, Yann Guérardel, Marie-Pierre Chapot-Chartier
Polysaccharides are ubiquitous components of the Gram-positive bacterial cell wall. In Lactococcus lactis, a polysaccharide pellicle (PSP) forms a layer at the cell surface. The PSP structure varies among lactococcal strains; in L. lactis MG1363, the PSP is composed of repeating hexasaccharide phosphate units. Here, we report the presence of an additional neutral polysaccharide in L. lactis MG1363 that is a rhamnan composed of α-l-Rha trisaccharide repeating units. This rhamnan is still present in mutants devoid of the PSP, indicating that its synthesis can occur independently of PSP synthesis...
September 12, 2017: MBio
https://www.readbyqxmd.com/read/28891366/efficacy-and-safety-of-b-cell-receptor-signaling-pathway-inhibitors-in-relapsed-refractory-chronic-lymphocytic-leukemia-a-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#13
Anna Puła, Konrad Stawiski, Marcin Braun, Elżbieta Iskierka-Jażdżewska, Tadeusz Robak
Ibrutinib and idelalisib, B-cell receptor (BCR) signaling pathway inhibitors, have been recently approved for use against relapsed/refractory chronic lymphocytic leukemia (CLL). To assess the efficacy and safety of BCR pathway inhibitors in relapsed/refractory CLL, we conducted a systematic review and meta-analysis of five randomized controlled trials (1866 patients). Our study demonstrated that BCR pathway inhibitors significantly prolonged progression-free survival (PFS; pooled HR = 0.24; 95% CI: 0.19-0...
September 11, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28891354/brca2-protects-mammalian-cells-from-heat-shock
#14
Yosuke Nakagawa, Atsuhisa Kajihara, Akihisa Takahashi, Akiho S Murata, Masaya Matsubayashi, Soichiro S Ito, Ichiro Ota, Takahiko Nakagawa, Masatoshi Hasegawa, Tadaaki Kirita, Takeo Ohnishi, Eiichiro Mori
PURPOSE: Heat shock induces DNA double-strand breaks (DSBs) in mammalian cells. Mammalian cells are capable of repairing DSBs by utilising the homologous recombination (HR) pathway. Breast cancer susceptibility gene 2 (BRCA2) is known to regulate the HR pathway. Here, we investigate the role of BRCA2 in repairing DNA damage induced by heat shock. MATERIALS AND METHODS: Chinese hamster lung fibroblast cell lines and human tongue squamous cell carcinoma SAS cells were used...
September 10, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28886696/inhibition-of-pi3k-akt-mtor-pathway-sensitizes-endometrial-cancer-cell-lines-to-parp-inhibitors
#15
Charles-André Philip, Ido Laskov, Marie-Claude Beauchamp, Maud Marques, Oreekha Amin, Joanna Bitharas, Roy Kessous, Liron Kogan, Tahira Baloch, Walter H Gotlieb, Amber Yasmeen
BACKGROUND: Phosphatase and Tensin homolog (PTEN) is a tumor suppressor gene. Loss of its function is the most frequent genetic alteration in endometrioid endometrial cancers (70-80%) and high grade tumors (90%). We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status. We also highlighted a direct pathway linking PTEN to DNA repair. METHODS: Using endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay...
September 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28886403/increased-mapk1-3-phosphorylation-in-luminal-breast-cancer-related-with-pik3ca-hotspot-mutations-and-prognosis
#16
Diana Ramirez-Ardila, A Mieke Timmermans, Jean A Helmijr, John W M Martens, Els M J J Berns, Maurice P H M Jansen
INTRODUCTION: While mutations in PIK3CA are most frequently (45%) detected in luminal breast cancer, downstream PI3K/AKT/mTOR pathway activation is predominantly observed in the basal subtype. The aim was to identify proteins activated in PIK3CA mutated luminal breast cancer and the clinical relevance of such a protein in breast cancer patients. MATERIALS AND METHODS: Expression levels of 171 signaling pathway (phospho-)proteins established by The Cancer Genome Atlas (TCGA) using reverse phase protein arrays (RPPA) were in silico examined in 361 breast cancers for their relation with PIK3CA status...
September 5, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28885730/low-angiomotin-p130-with-concomitant-high-yes-associated-protein-1-expression-is-associated-with-adverse-prognosis-of-advanced-gastric-cancer
#17
Soon Auck Hong, Myoung Won Son, Junhun Cho, Si-Hyong Jang, Hyun Ju Lee, Ji-Hye Lee, Hyun Deuk Cho, Mee-Hye Oh, Moon Soo Lee
Angiomotin (AMOT) promotes angiogenesis and plays a role in neovascularization during tumorigenesis. Recently, the AMOT isoform, AMOT-p130, was shown to exert a regulatory effect on Yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway. The specific roles of AMOT-p130 and YAP1 in advanced gastric cancer (AGC) are yet to be established. In this study, a total of 166 patients with AGC were enrolled, and AMOT-p130 and YAP1 levels were analyzed by immunohistochemistry using tissue microarrays...
September 8, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28884516/removing-vessel-constriction-on-the-embryonic-heart-results-in-changes-in-valve-gene-expression-morphology-and-hemodynamics
#18
Vinal Menon, John Eberth, Lorain Junor, Alexander J Potts, Marwa Belhaj, Donald J DiPette, Michael Jenkins, Jay D Potts
BACKGROUND: The formation of healthy heart valves throughout embryonic development is dependent on both genetic and epigenetic factors. Hemodynamic stimuli are important epigenetic regulators of valvulogenesis, but the resultant molecular pathways that control valve development are poorly understood. Here, we describe how the heart and valves recover from the removal of a partial constriction (banding) of the OFT/ventricle junction (OVJ) that temporarily alters blood flow velocity through the embryonic chicken heart (HH stage 16/17)...
September 7, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28879097/signatures-derived-from-increase-in-sharpin-gene-copy-number-are-associated-with-poor-prognosis-in-patients-with-breast-cancer
#19
Diane Ojo, Maryam Seliman, Damu Tang
We report three signatures produced from SHARPIN gene copy number increase (GCN-Increase) and their effects on patients with breast cancer (BC). In the Metabric dataset (n = 2059, cBioPortal), SHARPIN GCN-Increase occurs preferentially or mutual exclusively with mutations in TP53, PIK3CA, and CDH1. These genomic alterations constitute a signature (SigMut) that significantly correlates with reductions in overall survival (OS) in BC patients (n = 1980; p = 1.081e - 6). Additionally, SHARPIN GCN-Increase is associated with 4220 differentially expressed genes (DEGs)...
December 2017: BBA Clinical
https://www.readbyqxmd.com/read/28869449/propofol-induced-neurotoxicity-in-hescs-involved-in-activation-of-mir-206-puma-signal-pathway
#20
Yu Li, Changxin Jia, Dianlong Zhang, Guangzhen Ni, Xia Miao, Ruirong Tu
BACKGROUND AND OBJECTIVE: Studies in developing animals have demonstrated that when anesthetic agents, such as propofol, are early administered in life, it can lead to neuronal cell death and learning disabilities. However, the mechanisms causing these effects remains unknown. A recent report found that propofol could significantly upregulat miR-206 expression in the human ASCs. miR-206 could also induce apoptosis in human malignant cancers. Therefore, in this study, we hypothesized that propofol induces neurotoxicity in human embryonic stem cells (hESCs)...
August 23, 2017: Cancer Biomarkers: Section A of Disease Markers
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