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https://www.readbyqxmd.com/read/28651237/the-many-postures-of-noncanonical-wnt-signaling-in-development-and-diseases
#1
REVIEW
Qian Xiao, Zhengxi Chen, Xiaozhuang Jin, Runyi Mao, Zhenqi Chen
Wnt signaling regulates many aspects of vertebrate development. Its dysregulation causes developmental defects and diseases including cancer. The signaling can be categorized in two pathways: canonical and noncanonical. Canonical pathway plays a key role in regulating proliferation and differentiation of cells whilst noncanonical Wnt signaling mainly controls cellular polarity and motility. During development, noncanonical Wnt signaling is required for tissue formation. Recent studies have shown that noncanonical Wnt signaling is involved in adult tissue development and cancer progression...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#2
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and NK T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28650848/ser-thr-protein-kinase-b2-nadph-oxidase-2-signaling-in-thromboinflammation
#3
Jing Li, Jaehyung Cho
PURPOSE OF REVIEW: Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)2-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. RECENT FINDINGS: Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently...
June 24, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28650560/uncovering-the-role-of-brain-derived-neurotrophic-factor-bdnf-trkb-signaling-in-head-and-neck-malignancies
#4
REVIEW
Juliana Kern de Moraes, Vivian Petersen Wagner, Felipe Paiva Fonseca, Pablo Agustin Vargas, Caroline Brunetto de Farias, Rafael Roesler, Manoela Domingues Martins
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that was first known as responsible for sustain the growth, function and plasticity of neural cells. BDNF exerts its effects by binding to the tyrosine kinase receptor B (TrkB). The BDNF/TrkB axis has been reported to be overexpressed in several neurogenic and non-neurogenic tumors. Its higher expression was associated with a poor prognosis to patients affected by different human malignancies, tumor growth, invasion and metastasis; epithelial-mesenchymal transition (EMT) and resistance to chemotherapy...
June 26, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28649880/understanding-type-1-diabetes-through-proteomics
#5
Inne Crèvecoeur, Saurabh Vig, Chantal Mathieu, Lut Overbergh
Auto-immunity against pancreatic beta-cells leads to an absolute shortage of the hormone insulin, resulting in hyperglycemia and the onset of type 1 diabetes (T1D). Proteomic approaches have been used to elucidate the mechanisms of beta-cell dysfunction and death. Areas covered: In the present review, we discuss discoveries in the beta-cell proteome that have contributed to better insights in the role of the beta-cell in T1D. Techniques, such as 2D-DIGE and MALDI imaging, together with new approaches for sample preparation, including laser capture microdissection and immunopeptidomics, have resulted in novel mechanistic insights in the pathogenesis of T1D...
June 26, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28649661/inflammatory-breast-cancer-a-model-for-investigating-cluster-based-dissemination
#6
Mohit Kumar Jolly, Marcelo Boareto, Bisrat G Debeb, Nicola Aceto, Mary C Farach-Carson, Wendy A Woodward, Herbert Levine
Metastases claim more than 90% of cancer-related patient deaths and are usually seeded by a subset of circulating tumor cells shed off from the primary tumor. In circulation, circulating tumor cells are found both as single cells and as clusters of cells. The clusters of circulating tumor cells, although many fewer in number, possess much higher metastatic potential as compared to that of individual circulating tumor cells. In this review, we highlight recent insights into molecular mechanisms that can enable the formation of these clusters-(a) hybrid epithelial/mesenchymal phenotype of cells that couples their ability to migrate and adhere, and (b) intercellular communication that can spatially coordinate the cluster formation and provide survival signals to cancer cells...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649560/escaping-death-mitochondrial-redox-homeostasis-in-cancer-cells
#7
REVIEW
Francesco Ciccarese, Vincenzo Ciminale
Reactive oxygen species (ROS) are important signaling molecules that act through the oxidation of nucleic acids, proteins, and lipids. Several hallmarks of cancer, including uncontrolled proliferation, angiogenesis, and genomic instability, are promoted by the increased ROS levels commonly found in tumor cells. To counteract excessive ROS accumulation, oxidative stress, and death, cancer cells tightly regulate ROS levels by enhancing scavenging enzymes, which are dependent on the reducing cofactor nicotinamide adenine dinucleotide phosphate (NADPH)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28649374/screening-and-identification-of-novel-biologically-active-natural-compounds
#8
REVIEW
David Newman
With the advent of very rapid and cheap genome analyses and the linkage of these plus microbial metabolomics to potential compound structures came the realization that there was an immense sea of novel agents to be mined and tested. In addition, it is now recognized that there is significant microbial involvement in many natural products isolated from "nominally non-microbial sources". This short review covers the current screening methods that have evolved and one might even be tempted to say "devolved" in light of the realization that target-based screens had problems when the products entered clinical testing, with off-target effects being the major ones...
2017: F1000Research
https://www.readbyqxmd.com/read/28649369/recent-advances-in-understanding-contextual-tgf%C3%AE-signaling
#9
REVIEW
Arshad Ayyaz, Liliana Attisano, Jeffrey L Wrana
The appearance of the first animal species on earth coincides with the emergence of transforming growth factor β (TGFβ) pathways. The evolution of these animals into more complex organisms coincides with a progressively increased TGFβ repertoire through gene duplications and divergence, making secreted TGFβ molecules the largest family of morphogenetic proteins in humans. It is therefore not surprising that TGFβ pathways govern numerous aspects of human biology from early embryonic development to regeneration, hematopoiesis, neurogenesis, and immunity...
2017: F1000Research
https://www.readbyqxmd.com/read/28649368/wnt-target-genes-and-where-to-find-them
#10
REVIEW
Aravinda-Bharathi Ramakrishnan, Ken M Cadigan
Wnt/β-catenin signaling is highly conserved throughout metazoans, is required for numerous essential events in development, and serves as a stem cell niche signal in many contexts. Misregulation of the pathway is linked to several human pathologies, most notably cancer. Wnt stimulation results in stabilization and nuclear import of β-catenin, which then acts as a transcriptional co-activator. Transcription factors of the T-cell family (TCF) are the best-characterized nuclear binding partners of β-catenin and mediators of Wnt gene regulation...
2017: F1000Research
https://www.readbyqxmd.com/read/28649246/redirected-primary-human-chimeric-antigen-receptor-natural-killer-cells-as-an-off-the-shelf-immunotherapy-for-improvement-in-cancer-treatment
#11
REVIEW
Olaf Oberschmidt, Stephan Kloess, Ulrike Koehl
Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649232/ion-channels-of-pituitary-gonadotrophs-and-their-roles-in-signaling-and-secretion
#12
REVIEW
Stanko S Stojilkovic, Ivana Bjelobaba, Hana Zemkova
Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28648950/mechanisms-of-cholangiocyte-responses-to-injury
#13
REVIEW
Keisaku Sato, Fanyin Meng, Thao Giang, Shannon Glaser, Gianfranco Alpini
Cholangiocytes, epithelial cells that line the biliary epithelium, are the primary target cells for cholangiopathies including primary sclerosing cholangitis and primary biliary cholangitis. Quiescent cholangiocytes respond to biliary damage and acquire an activated neuroendocrine phenotype to maintain the homeostasis of the liver. The typical response of cholangiocytes is proliferation leading to bile duct hyperplasia, which is a characteristic of cholestatic liver diseases. Current studies have identified various signaling pathways that are associated with cholangiocyte proliferation/loss and liver fibrosis in cholangiopathies using human samples and rodent models...
June 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28648830/purinergic-p2y-receptors-molecular-diversity-and-implications-for-treatment-of-cardiovascular-diseases
#14
REVIEW
Akiyuki Nishimura, Caroline Sunggip, Sayaka Oda, Takuro Numaga-Tomita, Makoto Tsuda, Motohiro Nishida
Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes...
June 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28648331/il-35-as-a-newly-proposed-homeostasis-associated-molecular-pattern-plays-three-major-functions-including-anti-inflammatory-initiator-effector-and-blocker-in-cardiovascular-diseases
#15
Xinyuan Li, Pu Fang, William Y Yang, Hong Wang, Xiaofeng Yang
IL-35 is a new anti-inflammatory cytokine identified in 2007, which inhibits inflammation and immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. The unique initiator and effector anti-inflammatory properties of IL-35 bring tremendous interest in investigating its role during cardiovascular disease (CVD) development, in which inflammatory processes are firmly established as central to its development and complications. In this review, we update recent understanding of how IL-35 is produced and regulated in the cells...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28647886/wnt-signaling-in-ewing-sarcoma-osteosarcoma-and-malignant-peripheral-nerve-sheath-tumors
#16
REVIEW
Matthew G Pridgeon, Patrick J Grohar, Matthew R Steensma, Bart O Williams
PURPOSE OF REVIEW: Wnt signaling plays a central role in development and homeostasis, and its dysregulation is a common event in many types of human cancer. Here we explore in detail the contributions of Wnt signaling to the initiation and maintenance of three types of saroma: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors. This review provides an overview of the Wnt signaling pathway and explores in detail the current knowledge about its role in the initiation or maintenance of three tumor types: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors...
June 24, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28647871/cytoskeleton-as-a-target-of-quinolinic-acid-neurotoxicity-insight-from-animal-models
#17
REVIEW
Paula Pierozan, Regina Pessoa-Pureur
Cytoskeletal proteins are increasingly recognized as having important roles as a target of the action of different neurotoxins. In the last years, several works of our group have shown that quinolinic acid (QUIN) was able to disrupt the homeostasis of the cytoskeleton of neural cells and this was associated with cell dysfunction and neurodegeneration. QUIN is an excitotoxic metabolite of tryptophan metabolism and its accumulation is associated with several neurodegenerative diseases. In the present review, we provide a comprehensive view of the actions of QUIN upstream of glutamate receptors, eliciting kinase/phosphatase signaling cascades that disrupt the homeostasis of the phosphorylation system associated with intermediate filament proteins of astrocytes and neurons...
June 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28647857/ros-modulated-therapeutic-approaches-in-cancer-treatment
#18
REVIEW
Muhammad Hassan Raza, Sami Siraj, Abida Arshad, Usman Waheed, Fahad Aldakheel, Shatha Alduraywish, Muhammad Arshad
PURPOSE: Reactive oxygen species (ROS) are produced in cancer cells as a result of increased metabolic rate, dysfunction of mitochondria, elevated cell signaling, expression of oncogenes and increased peroxisome activities. Certain level of ROS is required by cancer cells, above or below which lead to cytotoxicity in cancer cells. This biochemical aspect can be exploited to develop novel therapeutic agents to preferentially and selectively target cancer cells. METHODS: We searched various electronic databases including PubMed, Web of Science, and Google Scholar for peer-reviewed english-language articles...
June 24, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28647837/targeting-metabolic-reprogramming-in-kras-driven-cancers
#19
REVIEW
Kenji Kawada, Kosuke Toda, Yoshiharu Sakai
Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect...
June 24, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28647645/adding-dimension-to-cellular-mechanotransduction-advances-in-biomedical-engineering-of-multiaxial-cell-stretch-systems-and-their-application-to-cardiovascular-biomechanics-and-mechano-signaling
#20
REVIEW
O Friedrich, D Schneidereit, Y A Nikolaev, V Nikolova-Krstevski, S Schürmann, A Wirth-Hücking, A L Merten, D Fatkin, B Martinac
Hollow organs (e.g. heart) experience pressure-induced mechanical wall stress sensed by molecular mechano-biosensors, including mechanosensitive ion channels, to translate into intracellular signaling. For direct mechanistic studies, stretch devices to apply defined extensions to cells adhered to elastomeric membranes have stimulated mechanotransduction research. However, most engineered systems only exploit unilateral cellular stretch. In addition, it is often taken for granted that stretch applied by hardware translates 1:1 to the cell membrane...
June 21, 2017: Progress in Biophysics and Molecular Biology
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