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https://www.readbyqxmd.com/read/28933058/extracellular-vesicles-how-they-interact-with-endothelium-potentially-contributing-to-metastatic-cancer-cell-implants
#1
REVIEW
Murray M Bern
Extracellular vesicles (EV) are blebs of cellular membranes, which entrap small portions of subjacent cytosol. They are released from a variety of cells, circulate in the blood for an unknown length of time and come to rest on endothelial surfaces. They contribute to an array of physiologic pathways, the complexity of which is still being investigated. They contribute to metastatic malignant cell implants and tumor-related angiogenesis, possibly abetted by the tissue factor that they carry. It is thought that the adherence of the EV to endothelium is dependent upon a combination of their P-selectin glycoprotein ligand-1 and exposed phosphatidylserine, the latter of which is normally hidden on the inner bilayer of the intact cellular membrane...
September 21, 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28930754/simvastatin-a-novel-stimulator-of-eryptosis-the-suicidal-erythrocyte-death
#2
Abdulla Al Mamun Bhuyan, Sigrid Nüßle, Hang Cao, Shaqiu Zhang, Florian Lang
BACKGROUND/AIMS: The 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase inhibitor simvastatin has been shown to trigger apoptosis of several cell types. The substance has thus been proposed as an additional treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the extracellular face of the erythrocyte cell membrane...
September 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28930717/inhibition-of-erythrocyte-cell-membrane-scrambling-by-asp3026
#3
Abdulla Al Mamun Bhuyan, Rosi Bissinger, Hang Cao, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma kinase (ALK) inhibitor ASP3026 is in clinical development for the treatment of ALK expressing non-small cell lung carcinoma (NSCLC). ASP3026 is in part effective by inducing apoptosis of tumor cells. Erythrocytes lack mitochondria and nuclei, key organelles in the execution of apoptosis, but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage...
September 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28928091/p2y12-antibody-inhibits-platelet-activity-and-protects-against-thrombogenesis
#4
Nicole R Hensch, Zubair A Karim, Joshua Pineda, Nicole Mercado, Fatima Z Alshbool, Fadi T Khasawneh
Given that platelet hyperactivity is known to give rise to thrombotic disorders, new and/or novel antiplatelet therapies are constantly being developed to add to, or to complement the current arsenal of agents. To this end, adenosine diphosphate (ADP) is an important platelet activator that acts by binding to the G-protein coupled P2Y1 and P2Y12 receptors. Although the contribution of the P2Y12 receptor to the genesis of thrombosis is well established, the parenteral arsenal of drugs targeting this receptor in clinical use is limited to cangrelor...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28927142/tumour-growth-suppressive-effect-of-arsenic-trioxide-in-squamous-cell-lung-carcinoma
#5
Leanne Lee Leung, Sze-Kwan Lam, Yuan-Yuan Li, James Chung-Man Ho
Lung squamous cell carcinoma (SCC) is the second most common subtype of non-small cell lung carcinoma. The anticancer effects of arsenic trioxide (ATO) in lung adenocarcinoma and small-cell lung cancer have previously been reported; however its effects in SCC remain unclear. An MTT assay and western blot analysis were performed to determine cell viability and protein expression, respectively, in the SK-MES-1 and SW900 SCC cell lines following treatment with ATO. Phosphatidylserine externalization, mitochondrial membrane depolarization and cell cycle distribution were studied using flow cytometry and the in vivo effects of ATO on tumour growth were investigated with a xenograft model...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926321/evaluation-of-platelet-activation-during-storage-in-leukocyte-depleted-platelet-concentrates
#6
Miodrag Vucic, Zoran Stanojkovic, Ana Antic, Jelana Vucic, Voja Pavlovic
Structural and functional changes in platelets during storage can lead to the loss of platelet reactivity and response. Our aim was to evaluate leukocyte-depleted platelet concentrates, obtained by in-line filtration on storage days 0, 3 and 5. In non-filtered platelet concentrates (NF-PC) group, 180 whole blood units were collected with quadruple blood bags and then compared to another group of 180 whole blood units (leukocyte-depleted platelet concentrates [LD-PC]), collected in Imuflex Whole Blood Filter Saving Platelets (WB-SP) bags with an integrated leukoreduction filter, with regard to the platelet quality and characteristics...
September 19, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28923840/apoptotic-bodies-elicit-gas6-mediated-migration-of-axl-expressing-tumor-cells
#7
Annelien Jm Zweemer, Cory B French, Joshua Mesfin, Simon Gordonov, Aaron S Meyer, Douglas A Lauffenburger
Metastases are a major cause of cancer mortality. AXL, a receptor tyrosine kinase (RTK) aberrantly expressed in many tumors, is a potent oncogenic driver of metastatic cell motility and has been identified as broadly relevant in cancer drug resistance. Despite its frequent association with changes in cancer phenotypes, the precise mechanism leading to AXL activation is incompletely understood. In addition to its ligand growth arrest specific-6 (Gas6), activation of AXL requires the lipid moiety phosphatidylserine (PS)...
September 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28923386/structure-based-design-synthesis-and-biological-evaluation-of-withaferin-a-analogues-as-potent-apoptotic-inducers
#8
Gabriel G Llanos, Liliana M Araujo, Ignacio A Jiménez, Laila M Moujir, Jaime Rodríguez, Carlos Jiménez, Isabel L Bazzocchi
Apoptosis inducers represent an attractive approach for the discovery and development of anticancer agents. Herein, we report on the development by molecular fine tuning of a withaferin A-based library of 63 compounds (2-64), 53 of them reported for the first time. Their antiproliferative evaluation on HeLa, A-549 and MCF-7 human tumor cell lines identified fifteen analogues displaying higher activity (IC50 values ranging 0.3-4.8 μM) than the lead (IC50 values ranging 1.3-10.1 μM) either in lag or log growth phases...
September 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28922657/methods-employed-in-cytofluorometric-assessment-of-eryptosis-the-suicidal-erythrocyte-death
#9
Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, Florian Lang
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28922409/purification-and-characterisation-of-the-yeast-plasma-membrane-atp-binding-cassette-transporter-pdr11p
#10
Katrine Rude Laub, Magdalena Marek, Lyubomir Dimitrov Stanchev, Sara Abad Herrera, Tamara Kanashova, Adèle Bourmaud, Gunnar Dittmar, Thomas Günther Pomorski
The ATP binding cassette (ABC) transporters Pdr11p and its paralog Aus1p are expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and are required for sterol uptake. However, the precise mechanism by which these ABC transporters facilitate sterol movement is unknown. In this study, an overexpression and purification procedure was developed with the aim to characterise the Pdr11p transporter. Engineering of Pdr11p variants fused at the C terminus with green fluorescent protein (Pdr11p-GFP) and containing a FLAG tag at the N terminus facilitated expression analysis and one-step purification, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28915027/structure-and-dynamics-of-membrane-proteins-and-membrane-associated-proteins-with-native-bicelles-from-eukaryotic-tissues
#11
Sean T Smrt, Adrian W Draney, Indira Singaram, Justin L Lorieau
In vitro studies of protein structure, function and dynamics typically preclude the complex range of molecular interactions found in living tissues. In vivo studies elucidate these complex relationships, yet they are typically incompatible with the extensive and controlled biophysical experiments available in vitro. We present an alternative approach by extracting membranes from eukaryotic tissues to produce native bicelles to capture the rich and complex molecular environment of in vivo studies while retaining the advantages of in vitro experiments...
September 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28914393/costunolide-induces-micronuclei-formation-chromosomal-aberrations-cytostasis-and-mitochondrial-mediated-apoptosis-in-chinese-hamster-ovary-cells
#12
Soma Shiva Nageswara Rao Singireesu, Sunil Misra, Sujan Kumar Mondal, Suresh Yerramsetty, Nivedita Sahu, Suresh Babu K
Costunolide (CE) is a sesquiterpene lactone well-known for its antihepatotoxic, antiulcer, and anticancer activities. The present study focused on the evaluation of the cytogenetic toxicity and cellular death-inducing potential of CE in CHO cells, an epithelial cell line derived from normal ovary cells of Chinese hamster. The cytotoxic effect denoting MTT assay has shown an IC50 value of 7.56 μM CE, where 50% proliferation inhibition occurs. The oxidative stress caused by CE was confirmed based on GSH depletion induced cell death, conspicuously absent in N-acetylcysteine (GSH precursor) pretreated cells...
September 15, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28912276/cavin-2-regulates-the-activity-and-stability-of-endothelial-nitric-oxide-synthase-enos-in-angiogenesis
#13
Gandhi T K Boopathy, Madhura Kulkarni, Sze Yuan Ho, Adrian Boey, Edmond Wei Min Chua, Veluchamy A Barathi, Tom J Carney, Xiaomeng Wang, Wanjin Hong
Angiogenesis is a highly regulated process for formation of new blood vessels from pre-existing ones. Angiogenesis is dysregulated in various pathologies, including age-related macular degeneration, arthritis, and cancer. Inhibiting pathological angiogenesis therefore represents a promising therapeutic strategy for treating these disorders, highlighting the need to study angiogenesis in more detail. To this end, identifying the genes essential for blood vessel formation and elucidating their function are crucial for a complete understanding of angiogenesis...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911832/association-of-silent-infarcts-in-sickle-cell-anemia-with-decreased-annexin-a5-resistance
#14
Kerry A Morrone, Lydia H Pecker, Jacob Rand, Jennifer Davila, Suzette Oyeku, Jane A Little, Xue Xiaonan, Deepa Manwani
BACKGROUND: Sickle cell anemia (SCA) is characterized by abnormally shaped, adhesive RBCs that interact with white blood cells and the endothelium, leading to chronic hemolysis, vasculopathy and a prothrombotic state. About 10% of subjects with a thrombotic event in the general population will have an associated antiphospholipid (aPL) antibody. One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of the potent anticoagulant annexin A5 or Annexin A5 resistance (A5R)...
September 4, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28910348/the-effect-of-corn-trypsin-inhibitor-anti-tissue-factor-pathway-inhibitor-antibodies-and-phospholipids-on-microvesicle-associated-thrombin-generation-in-patients-with-pancreatic-cancer-and-healthy-controls
#15
Marit Hellum, Isabel Franco-Lie, Reidun Øvstebø, Truls Hauge, Carola E Henriksson
Circulating microvesicles (MVs) are suggested to be important contributors to cancer-associated thrombosis due to the presence of surface-bound procoagulant molecules like tissue factor (TF) and phosphatidylserine (PS). Pancreatic cancer is considered to be one of the most prothrombotic malignancies. The aim of this study was to describe the impact of analytical variables on MV-associated thrombin generation in patients with pancreatic cancer and in healthy controls. MVs were isolated from citrated plasma and added to pooled normal plasma (PNP)...
2017: PloS One
https://www.readbyqxmd.com/read/28905705/mucilaginibacter-terrae-sp-nov-isolated-from-antarctic-soil
#16
Ivo Sedláček, Roman Pantůček, Stanislava Králová, Ivana Mašlaňová, Pavla Holochová, Eva Staňková, Roman Sobotka, Miloš Barták, Hans-Jürgen Busse, Pavel Švec
A bacterial strain designated CCM 8645T was isolated from a soil sample collected nearby a mummified seal carcass in the northern part of James Ross Island, Antarctica. The cells were short rods, Gram-stain-negative, non-motile, catalase and oxidase positive, and produced a red-pink pigment on R2A agar. A polyphasic taxonomic approach based on 16S rRNA gene sequencing, extensive biotyping using conventional tests and commercial identification kits and chemotaxonomic analyses were applied to clarify its taxonomic position...
September 14, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28905392/cryopreserved-platelets-demonstrate-reduced-activation-responses-and-impaired-signaling-after-agonist-stimulation
#17
Lauren Waters, Matthew P Padula, Denese C Marks, Lacey Johnson
BACKGROUND: Room temperature-stored (20-24°C) platelets (PLTs) have a shelf life of 5 days, making it logistically challenging to supply remote medical centers with PLT products. Cryopreservation of PLTs in dimethyl sulfoxide (DMSO) and storage at -80°C enables an extended shelf life up to 2 years. Although cryopreserved PLTs have been widely characterized under resting conditions, their ability to undergo agonist-induced activation is yet to be fully explored. STUDY DESIGN AND METHODS: Buffy coat PLTs were cryopreserved at -80°C with 5% to 6% DMSO and sampled before freezing and after thawing...
September 14, 2017: Transfusion
https://www.readbyqxmd.com/read/28905214/mir-217-5p-induces-apoptosis-by-directly-targeting-prkci-bag3-itgav-and-mapk1-in-colorectal-cancer-cells
#18
Marion Flum, Michael Kleemann, Helga Schneider, Benjamin Weis, Simon Fischer, René Handrick, Kerstin Otte
Apoptosis is a genetically directed process of programmed cell death. A variety of microRNAs (miRNAs), endogenous single-stranded non-coding RNAs of about 22 nucleotides in length have been shown to be involved in the regulation of the intrinsic or extrinsic apoptotic pathways. There is increasing evidence that the aberrant expression of miRNAs plays a causal role in the development of diseases such as cancer. This makes miRNAs promising candidate molecules as therapeutic targets or agents. MicroRNA (miR)-217-5p has been implicated in carcinogenesis of various cancer entities, including colorectal cancer...
September 14, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28904555/acyclic-sesquiterpenes-from-the-fruit-pericarp-of-sapindus-saponaria-induce-ultrastructural-alterations-and-cell-death-in-leishmania-amazonensis
#19
Amanda Louzano Moreira, Débora Botura Scariot, Bruna Luíza Pelegrini, Greisiele Lorena Pessini, Tânia Ueda-Nakamura, Celso Vataru Nakamura, Izabel Cristina Piloto Ferreira
Previous studies reported antiprotozoal activities of Sapindus saponaria L. The aim of this work was the evaluation of antileishmanial activity and mechanism of action of extract and fractions of S. saponaria L. Hydroethanolic extract (EHA) obtained from fruit pericarps was fractionated using solid-phase extraction in a reversed phase, resulting in fractions enriched with saponins (SAP fraction) and acyclic sesquiterpene oligoglycosides (OGSA fraction). The activities of EHA, SAP, and OGSA were evaluated by antiproliferative assays with promastigote and intracellular amastigote forms...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28903085/multiscale-molecular-dynamics-simulations-of-lipid-interactions-with-p-glycoprotein-in-a-complex-membrane
#20
Laura Domicevica, Heidi Koldsø, Philip C Biggin
P-glycoprotein (P-gp) can transport a wide range of very different hydrophobic organic molecules across the membrane. Its ability to extrude molecules from the cell creates delivery problems for drugs that target proteins in the central nervous system (CNS) and also causes drug-resistance in many forms of cancer. Whether a drug will be susceptible to export by P-gp is difficult to predict and currently this is usually assessed with empirical and/or animal models. Thus, there is a need to better understand how P-gp works at the molecular level in order to fulfil the 3Rs: Refinement, reduction and replacement of animals in research...
September 2, 2017: Journal of Molecular Graphics & Modelling
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