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https://www.readbyqxmd.com/read/28538979/stanniocalcin-1-is-an-ocular-hypotensive-agent-and-a-downstream-effector-molecule-that-is-necessary-for-the-intraocular-pressure-lowering-effects-of-latanoprost
#1
Gavin W Roddy, Kimberly B Viker, Nelson S Winkler, Cindy K Bahler, Bradley H Holman, David Sheikh-Hamad, Uttio Roy Chowdhury, W Daniel Stamer, Michael P Fautsch
Purpose: To identify downstream signaling molecules through which intraocular pressure (IOP) is lowered following treatment with the prostaglandin analog latanoprost. Methods: Total RNA and protein isolated from primary human Schlemm's canal cells (n = 3) treated with latanoprost (free acid; 100 nM) were processed for quantitative PCR and Western blot analysis. IOP was evaluated in stanniocalcin-1 (STC-1-/-) and wild-type mice following treatment with latanoprost or Rho kinase inhibitor Y27632...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28538945/purpuric-drug-eruptions-caused-by-epidermal-growth-factor-receptor-inhibitors-for-non-small-cell-lung-cancer-a-clinicopathologic-study-of-32-cases
#2
Yung-Tsu Cho, Kai-Lung Chen, Yi-Shuan Sheen, Che-Wen Yang, Jau-Yu Liau, Yu-Pin Cheng, Chia-Yu Chu
Importance: Purpuric skin lesions have only rarely been reported in patients receiving epidermal growth factor receptor inhibitors. However, their clinical and histopathologic presentations have varied considerably. Objective: To characterize purpuric skin eruptions caused by epidermal growth factor receptor inhibitors. Design, Setting, and Participants: This prospective study enrolled 32 patients who presented to an integrated dermato-oncologic clinic in a tertiary referral medical center with purpuric skin lesions after using epidermal growth factor receptor inhibitors from January 1, 2013, through December 31, 2015...
May 24, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#3
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#4
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#5
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28538688/in-silico-study-and-bioprospection-of-the-antibacterial-and-antioxidant-effects-of-flavone-and-its-hydroxylated-derivatives
#6
Camila de Albuquerque Montenegro, Gregório Fernandes Gonçalves, Abrahão Alves de Oliveira Filho, Andressa Brito Lira, Thays Thyara Mendes Cassiano, Natanael Teles Ramos de Lima, José Maria Barbosa-Filho, Margareth de Fátima Formiga Melo Diniz, Hilzeth Luna Freire Pessôa
Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives: 3-hydroxyflavone, 5-hydroxyflavone and 6-hydroxyflavone. To do so, we investigated their pharmacological characteristics, using in silico tests that indicate likelihood of activity or inactivity, with the PASS online software, and the antimicrobial potential against Gram positive and Gram negative bacteria was also analyzed, including bacteria of clinical importance...
May 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28538683/metabolic-investigations-of-the-molecular-mechanisms-associated-with-parkinson-s-disease
#7
REVIEW
Robert Powers, Shulei Lei, Annadurai Anandhan, Darrell D Marshall, Bradley Worley, Ronald L Cerny, Eric D Dodds, Yuting Huang, Mihalis I Panayiotidis, Aglaia Pappa, Rodrigo Franco
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies) and the associated loss of dopaminergic cells in the substantia nigra. Mutations in genes such as α-synuclein (SNCA) account for only 10% of PD occurrences. Exposure to environmental toxicants including pesticides and metals (e.g., paraquat (PQ) and manganese (Mn)) is also recognized as an important PD risk factor. Thus, aging, genetic alterations, and environmental factors all contribute to the etiology of PD...
May 24, 2017: Metabolites
https://www.readbyqxmd.com/read/28538663/the-cytokine-flt3-ligand-in-normal-and-malignant-hematopoiesis
#8
REVIEW
Panagiotis Tsapogas, Ciaran James Mooney, Geoffrey Brown, Antonius Rolink
The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. Activating mutations of Flt3 are frequently found in acute myeloid leukemia (AML) patients and associated with a poor clinical prognosis. In the present review we provide an overview of our current knowledge on the role of FL in the generation of blood cell lineages...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538623/impact-of-a-novel-pi3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#9
George E Black, Kyle K Sokol, Donald M Moe, Jon Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhalo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental PI3-kinase inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage associated molecular patterns (DAMPs) METHODS: 16 swine were studied using LY294002 (LY), a non-selective PI3-KI: Animals were assigned to Trauma only (TO, N=3); LY drug only (LYO, N=3); and Experimental (N=10), trauma + drug (LY+T) groups...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28538438/differential-regulation-of-the-autophagy-and-proteasome-pathways-in-skeletal-muscles-in-sepsis
#10
Flavia Stana, Marija Vujovic, Dominique Mayaki, Jean-Philippe Leduc-Gaudet, Philippe Leblanc, Laurent Huck, Sabah N A Hussain
OBJECTIVES: Skeletal muscle fiber atrophy develops in response to severe sepsis, but it is unclear as to how the proteolytic pathways that are involved in its development are differentially regulated. We investigated the link between sepsis-induced fiber atrophy and activation of the proteasome and autophagy pathways and whether the degree of activation is more severe and sustained in limb muscles than it is in the diaphragm. DESIGN: Randomized controlled experiment...
May 22, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28538414/clinical-predictors-for-the-manifestation-of-late-gadolinium-enhancement-after-acute-myocardial-infarction
#11
Nadine Abanador-Kamper, Lars Kamper, Marc Vorpahl, Hilmar Brinkmann, Vasiliki Karamani, Patrick Haage, Melchior Seyfarth
Despite prompt revascularization, some patients with acute myocardial infarction (AMI) develop myocardial scars, which can be visualized by late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). Our goal was to identify angiographic findings that were predictive for scar development in patients after reperfused AMI.We examined 136 patients after first ST-elevated myocardial infarction by CMR after a median of 4 days (range: 2-7). Patients with manifestation of LGE were matched to patients without LGE by means of age and gender...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538405/marked-response-to-nab-paclitaxel-in-egfr-mutated-lung-neuroendocrine-carcinoma-a-case-report
#12
Jin-Yan Liang, Fan Tong, Fei-Fei Gu, Yang-Yang Liu, Yu-Lan Zeng, Xiao-Hua Hong, Kai Zhang, Li Liu
RATIONALE: Lung cancer is the leading cause of cancer-related death in the world. Tyrosine kinase inhibitors (TKIs), which target mutated epidermal growth factor receptor (EGFR), have been the first-line treatment of late-stage lung adenocarcinoma harboring EGFR mutation. EGFR mutations are mostly identified in lung adenocarcinoma. However, it is rarely seen in lung neuroendocrine carcinoma, and treatment strategies remain under reported. PATIENT CONCERNS: Here, we describe a 54-year-old Chinese man diagnosed with lung adenocarcinoma (cT4N3M1b, stage IV) with neuroendocrine differentiation and L858R mutation on exon 21...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538401/atrial-fibrillation-was-changed-into-sinus-bradycardia-in-a-ros1-positive-advanced-lung-adenocarcinoma-patient-who-achieved-durable-response-to-crizotinib-a-case-report-and-literature-review
#13
Lan Liu, Jing Wu, Wei Zhao, Mei-Juan Huang
RATIONAL: The c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearrangements represent a new and rare genetic subtype of non-small-cell lung cancer. In recent years, the use of crizotinib in ROS1-rearranged lung cancer exhibits significant clinical efficacy. Crizotinib is generally well tolerated and the most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac, and endocrine abnormalities. From a cardiac perspective, crizotinib is associated with 2 main cardiac effects, QT interval prolongation and bradycardia...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538307/can-cold-water-immersion-enhance-recovery-in-elite-olympic-weightlifters-an-individualized-perspective
#14
Jan Schimpchen, Maximilian Wagner, Alexander Ferrauti, Michael Kellmann, Mark Pfeiffer, Tim Meyer
Schimpchen, J, Wagner, M, Ferrauti, A, Kellmann, M, Pfeiffer, M, and Meyer, T. Can cold water immersion enhance recovery in elite Olympic weightlifters? An individualized perspective. J Strength Cond Res 31(6): 1569-1576, 2017-We investigated whether cold water immersion (CWI) after intensive training sessions can enhance recovery in elite Olympic weightlifters, taking into account each athlete's individual response pattern. The entire German male Olympic weightlifting national team participated in the study (n = 7), ensuring collection of data from elite athletes only...
June 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28538253/immune-myopathy-with-perimysial-pathology-associated-with-interstitial-lung-disease-and-anti-ej-antibodies
#15
Patrick M Kwon, Lan Zhou, Rajeev Motiwala, Leslie D Kerr, Susan C Shin
OBJECTIVES: We report a case of immune myopathy with perimysial pathology associated with anti-glycyl-transfer RNA synthetase (anti-EJ) antibody and an excellent treatment response. METHODS: Chart review. RESULTS: A 36-year-old woman presented with 3 months of fatigue, weight loss, progressive weakness in a scapuloperoneal distribution, and dysphagia. Nerve conduction studies, electromyography, and ultrasound suggested an irritable myopathy...
June 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/28538163/metabolic-signatures-of-t-cells-and-macrophages-in-rheumatoid-arthritis
#16
REVIEW
Cornelia M Weyand, Markus Zeisbrich, Jörg J Goronzy
In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors...
May 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28538157/cell-and-tissue-scale-forces-coregulate-fgfr2-dependent-tetrads-and-rosettes-in-the-mouse-embryo
#17
Jun Wen, Hirotaka Tao, Kimberly Lau, Haijiao Liu, Craig A Simmons, Yu Sun, Sevan Hopyan
What motivates animal cells to intercalate is a longstanding question that is fundamental to morphogenesis. A basic mode of cell rearrangement involves dynamic multicellular structures called tetrads and rosettes. The contribution of cell-intrinsic and tissue-scale forces to the formation and resolution of these structures remains unclear, especially in vertebrates. Here, we show that Fgfr2 regulates both the formation and resolution of tetrads and rosettes in the mouse embryo, possibly in part by spatially restricting atypical protein kinase C, a negative regulator of non-muscle myosin IIB...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538104/wnt5a-regulates-the-expression-of-ror2-tyrosine-kinase-receptor-in-ovarian-cancer-cells
#18
Ghamartaj Hossein, Somayeh Arabzadeh, Zahra Salehi-Doulabi, Zeynab Dehghani-Ghobadi, Yasaman Heidarian, Maryam Talebi-Juybari
Wnt5A and Receptor tyrosine kinase-like orphan receptor 2 (ROR2) proteins both regulate developmental processes, cell movement, and cell polarity. The purpose of the present study was to evaluate a possible regulatory role of Wnt5A on ROR2 expression in human ovarian cancer cell lines. Moreover, the expression of Wnt5A and ROR2 mRNA and protein levels were assessed in human epithelial serous ovarian cancer (HSOC) specimens. ROR2 was strongly decreased in cells treated with siRNA against Wnt5A compared to scramble-treated or lipofectamine-treated cells (P<0...
May 24, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28537930/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#19
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#20
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
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