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https://www.readbyqxmd.com/read/29050361/bet-inhibitors-as-novel-therapeutic-agents-in-breast-cancer
#1
REVIEW
Alberto Ocaña, Cristina Nieto-Jiménez, Atanasio Pandiella
Tumoral cells not only depend on oncogenic abnormalities to maintain its malignant phenotype but on non-oncogenic vulnerabilities. Targeting epigenomics can modify specific cellular functions required for malignant transformation. The Bromodomain (BRD) family mediates their effect by recruiting proteins of the transcription machinery, recognizing acetylated-lysine residues in nucleosomal histones. Bromodomain and extra-terminal (BET) inhibitors have shown to produce growth inhibition in several tumors through the inhibition of the expression of several transcription factors...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050357/oncomir-17-5p-alarm-signal-in-cancer
#2
REVIEW
Madhusudhan Reddy Bobbili, Robert M Mader, Johannes Grillari, Hanna Dellago
Soon after microRNAs entered the stage as novel regulators of gene expression, they were found to regulate -and to be regulated by- the development, progression and aggressiveness of virtually all human types of cancer. Therefore, miRNAs in general harbor a huge potential as diagnostic and prognostic markers as well as potential therapeutic targets in cancer. The miR-17-92 cluster was found to be overexpressed in many human cancers and to promote unrestrained cell growth, and has therefore been termed onco-miR-1...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#3
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048338/g-protein-dependent-signal-transduction-and-ubiquitination-in-dictyostelium
#4
REVIEW
Barbara Pergolizzi, Salvatore Bozzaro, Enrico Bracco
Signal transduction through G-protein-coupled receptors (GPCRs) is central for the regulation of virtually all cellular functions, and it has been widely implicated in human diseases. These receptors activate a common molecular switch that is represented by the heterotrimeric G-protein generating a number of second messengers (cAMP, cGMP, DAG, IP3, Ca(2+) etc.), leading to a plethora of diverse cellular responses. Spatiotemporal regulation of signals generated by a given GPCR is crucial for proper signalling and is accomplished by a series of biochemical modifications...
October 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29047224/ral-signaling-pathway-in-health-and-cancer
#5
REVIEW
Adel Rezaei Moghadam, Elham Patrad, Elham Tafsiri, Warner Peng, Benjamin Fangman, Timothy J Pluard, Anthony Accurso, Michael Salacz, Kushal Shah, Brandon Ricke, Danse Bi, Kyle Kimura, Leland Graves, Marzieh Khajoie Najad, Roya Dolatkhah, Zohreh Sanaat, Mina Yazdi, Naeimeh Tavakolinia, Mohammad Mazani, Mojtaba Amani, Saeid Ghavami, Robyn Gartell, Colleen Reilly, Zaid Naima, Tuba Esfandyari, Faris Farassati
The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells...
October 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29047191/wnt-signalling-pathways-in-skin-development-and-epidermal-stem-cells
#6
REVIEW
Anthony Veltri, Christopher Lang, Wen-Hui Lien
Mammalian skin and its appendages constitute the integumentary system forming a barrier between the organism and its environment. During development, skin epidermal cells divide rapidly and stratify into a multilayered epithelium, as well as invaginate downward in the underlying mesenchyme to form hair follicles (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal regeneration is fueled by epidermal stem cells (SCs) located in the basal layer of the IFE and the outer layer of the bulge in the HF...
October 19, 2017: Stem Cells
https://www.readbyqxmd.com/read/29047101/subcellular-redox-signaling
#7
Liping Zhu, Yankai Lu, Jiwei Zhang, Qinghua Hu
Oxidative and antioxidative system of cells and tissues maintains a balanced state under physiological conditions. A disruption in this balance of redox status has been associated with numerous pathological processes. Reactive oxygen species (ROS) as a major redox signaling generates in a spatiotemporally dependent manner. Subcellular organelles such as mitochondria, endoplasmic reticulum, plasma membrane and nuclei contribute to the production of ROS. In addition to downstream effects of ROS signaling regulated by average ROS changes in cytoplasm, whether subcelluar ROS mediate biological effect(s) has drawn greater attentions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29047088/lung-ischaemia-reperfusion-injury-the-role-of-reactive-oxygen-species
#8
Oleg Pak, Akylbek Sydykov, Djuro Kosanovic, Ralph T Schermuly, Alexander Dietrich, Katrin Schröder, Ralf P Brandes, Thomas Gudermann, Natascha Sommer, Norbert Weissmann
Lung ischaemia-reperfusion injury (LIRI) occurs in many lung diseases and during surgical procedures such as lung transplantation. The re-establishment of blood flow and oxygen delivery into the previously ischaemic lung exacerbates the ischaemic injury and leads to increased microvascular permeability and pulmonary vascular resistance as well as to vigorous activation of the immune response. These events initiate the irreversible damage of the lung with subsequent oedema formation that can result in systemic hypoxaemia and multi-organ failure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29047082/a-brief-overview-of-nitric-oxide-and-reactive-oxygen-species-signaling-in-hypoxia-induced-pulmonary-hypertension
#9
Ariel Jaitovich, David Jourd'heuil
Pulmonary hypertension (PH) is characterized by increased vasoconstriction and smooth muscle cell hyperplasia driving pathological vascular remodeling of arterial vessels. In this short review, we discuss the primary source of reactive oxygen species (ROS) and nitric oxide (NO) relevant to PH and the mechanism by which dysregulation of their production contributes to PH. Specifically, hypoxia-induced PH is associated with diminished endothelial nitric oxide synthase (eNOS)-derived NO production and increased production of superoxide (O2(•-)) through eNOS uncoupling and defective mitochondrial respiration...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29047081/redox-regulation-of-the-superoxide-dismutases-sod3-and-sod2-in-the-pulmonary-circulation
#10
Daniel Hernandez-Saavedra, Kalin Swain, Rubin Tuder, Steen V Petersen, Eva Nozik-Grayck
When evaluating the role of redox-regulating signaling in pulmonary vascular diseases, it is intriguing to consider the modulation of key antioxidant enzymes like superoxide dismutase (SOD) because SOD isoforms are regulated by redox reactions, and, in turn, modulate downstream redox sensitive processes. The emerging field of redox biology is built upon understanding the regulation and consequences of tightly controlled and specific reduction-oxidation reactions that are critical for diverse cellular processes including cell signaling...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29047077/adventitial-fibroblast-nox4-expression-and-ros-signaling-in-pulmonary-arterial-hypertension
#11
Scott A Barman, David Fulton
Pulmonary arterial hypertension (PAH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4), a constitutively active enzyme, has been associated with oxygen sensing, vasomotor control, cellular proliferation, differentiation, migration, apoptosis, senescence, fibrosis, and angiogenesis. Further, elevated expression of Nox4 has been reported in a number of cardiovascular diseases, including atherosclerosis, hypertension, cardiac failure, ischemic stroke, and PAH...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29046875/asymmetric-rna-distribution-among-cells-and-their-secreted-exosomes-biomedical-meaning-and-considerations-on-diagnostic-applications
#12
REVIEW
Marco Ragusa, Cristina Barbagallo, Matilde Cirnigliaro, Rosalia Battaglia, Duilia Brex, Angela Caponnetto, Davide Barbagallo, Cinzia Di Pietro, Michele Purrello
Over the past few years, exosomes and their RNA cargo have been extensively studied because of the fascinating biological roles they play in cell-to-cell communication, including the signal exchange among cancer, stromal, and immune cells, leading to modifications of tumor microenvironment. RNAs, especially miRNAs, stored within exosomes, seem to be among the main determinants of such signaling: their sorting into exosomes appears to be cell-specific and related to cellular physiopathology. Accordingly, the identification of exosomal miRNAs in body fluids from pathological patients has become one of the most promising activity in the field of biomarker discovery...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29046438/on-myelinated-axon-plasticity-and-neuronal-circuit-formation-and-function
#13
Rafael G Almeida, David A Lyons
Studies of activity-driven nervous system plasticity have primarily focused on the gray matter. However, MRI-based imaging studies have shown that white matter, primarily composed of myelinated axons, can also be dynamically regulated by activity of the healthy brain. Myelination in the CNS is an ongoing process that starts around birth and continues throughout life. Myelin in the CNS is generated by oligodendrocytes and recent evidence has shown that many aspects of oligodendrocyte development and myelination can be modulated by extrinsic signals including neuronal activity...
October 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29046344/kinetochore-microtubule-interactions-in-chromosome-segregation-lessons-from-yeast-and-mammalian-cells
#14
REVIEW
Geethu Emily Thomas, Marira R Renjith, Tapas K Manna
Chromosome congression and segregation require robust yet dynamic attachment of the kinetochore with the spindle microtubules. Force generated at the kinetochore-microtubule interface plays a vital role to drive the attachment, as it is required to move chromosomes and to provide signal to sense correct attachments. To understand the mechanisms underlying these processes, it is critical to describe how the force is generated and how the molecules at the kinetochore-microtubule interface are organized and assembled to withstand the force and respond to it...
October 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29040423/title-therapeutic-strategies-utilising-sdf-1%C3%AE-in-ischaemic-cardiomyopathy
#15
Oliver J Ziff, Daniel I Bromage, Derek M Yellon, Sean M Davidson
Heart failure is rapidly increasing in prevalence and will redraw the global landscape for cardiovascular health. Alleviating and repairing cardiac injury associated with myocardial infarction (MI) is key to improving this burden. Homing signals mobilise and recruit stem cells to the ischaemic myocardium where they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1α and its associated receptor CXCR4 are upregulated after MI and appear to be important in this context. Activation of CXCR4 promotes both cardiomyocyte survival and stem cell migration towards the infarcted myocardium...
October 13, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29039818/the-role-of-b-cell-targeting-in-chronic-graft-versus-host-disease
#16
REVIEW
Ruben Rhoades, Sameh Gaballa
Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality following allogeneic stem cell transplantation. Current therapies, including corticosteroids and calcineurin inhibitors, are only effective in roughly 50% of cases; therefore, new treatment strategies are under investigation. What was previously felt to be a T cell disease has more recently been shown to involve activation of both T and B cells, as well as a number of cytokines. With a better understanding of its pathophysiology have come more expansive preclinical and clinical trials, many focused on B cell signaling...
October 17, 2017: Biomedicines
https://www.readbyqxmd.com/read/29039786/tgf-%C3%AE-induced-endothelial-mesenchymal-transition-in-fibrotic-diseases
#17
REVIEW
Evangelia Pardali, Gonzalo Sanchez-Duffhues, Maria Catalina Gomez-Puerto, Peter Ten Dijke
Fibrotic diseases are characterized by net accumulation of extracellular matrix proteins in affected organs leading to their dysfunction and ultimate failure. Myofibroblasts have been identified as the cells responsible for the progression of the fibrotic process, and they originate from several sources, including quiescent tissue fibroblasts, circulating CD34⁺ fibrocytes and the phenotypic conversion of various cell types into activated myofibroblasts. Several studies have demonstrated that endothelial cells can transdifferentiate into mesenchymal cells through a process termed endothelial- mesenchymal transition (EndMT) and that this can give rise to activated myofibroblasts involved in the development of fibrotic diseases...
October 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29039764/human-chorionic-gonadotropin-as-a-pivotal-endocrine-immune-regulator-initiating-and-preserving-fetal-tolerance
#18
REVIEW
Anne Schumacher
The pregnancy hormone, human chorionic gonadotropin (hCG), is crucially involved in processes such as implantation and placentation, two milestones of pregnancy whose successful progress is a prerequisite for adequate fetal growth. Moreover, hCG determines fetal fate by regulating maternal innate and adaptive immune responses allowing the acceptance of the foreign fetal antigens. As one of the first signals provided by the embryo to its mother, hCG has the potential to regulate very early pregnancy-driven immune responses, allowing the establishment and preservation of fetal tolerance...
October 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29039083/myristoylated-alanine-rich-c-kinase-substrate-marcks-a-multirole-signaling-protein-in-cancers
#19
REVIEW
Lon Wolf R Fong, David C Yang, Ching-Hsien Chen
Emerging evidence implicates myristoylated alanine-rich C-kinase substrate (MARCKS), a major substrate of protein kinase C (PKC), in a critical role for cancer development and progression. MARCKS is tethered to the plasma membrane but can shuttle between the cytosol and plasma membrane via the myristoyl-electrostatic switch. Phosphorylation of MARCKS by PKC leads to its translocation from the plasma membrane to the cytosol where it functions in actin cytoskeletal remodeling, Ca(2+) signaling through binding to calmodulin, and regulation of exocytic vesicle release in secretory cells such as neurons and airway goblet cells...
October 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29039064/developments-in-hematopoietic-stem-cell-expansion-and-gene-editing-technologies
#20
Dogacan Yucel, Fatih Kocabas
Hematopoietic stem cells (HSCs) are rare cells, which housed in the adult bone marrow. They maintain all types of differentiated blood cells throughout life. Due to limited availability of HSCs for transplantation, treatment of various inherited bone marrow disorders and anemia requires the development of HSC expansion and gene editing technologies. To this end, various studies addressed the use of cytokines and growth factors for HSC expansion. Major hurdle with these studies was found to be spontaneous differentiation of HSCs into different lineages during ex vivo procedure...
October 17, 2017: Advances in Experimental Medicine and Biology
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