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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/27919797/maximising-the-potential-of-akt-inhibitors-as-anti-cancer-treatments
#1
REVIEW
Jessica S Brown, Udai Banerji
PI3K/AKT signalling is commonly disrupted in human cancers, with AKT being a central component of the pathway, influencing multiple processes that are directly involved in tumourigenesis. Targeting AKT is therefore a highly attractive anti-cancer strategy with multiple AKT inhibitors now in various stages of clinical development. In this review, we summarise the role and regulation of AKT signalling in normal cellular physiology. We highlight the mechanisms by which AKT signalling can be hyperactivated in cancers and discuss the past, present and future clinical strategies for AKT inhibition in oncology...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27919796/the-bad-seed-gardener-deubiquitinases-in-the-cancer-stem-cell-signaling-network-and-therapeutic-resistance
#2
REVIEW
Guan-Zhong Qiu, Wei Sun, Ming-Zhu Jin, Jing Lin, Pei-Gang Lu, Wei-Lin Jin
Tumors are comprised of highly heterogeneous populations of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumors in vivo. These rare cancer stem cells (CSCs) have been regarded as the "bad seeds" accounted for tumor initiation, progression, metastasis, relapse and therapeutic resistance. CSC-targeted therapy seems to be a better avenue for radical cure of cancer. Deubiquitinases (DUBs), specifically disassembling ubiquitin chains, have been demonstrated to play an important role in rigidly maintaining the balance between ubiquitination and deubiquitination for protein quality control and homeostasis in normal circumstances...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27919795/current-and-novel-insights-into-the-neurophysiology-of-migraine-and-its-implications-for-therapeutics
#3
REVIEW
Simon Akerman, Marcela Romero-Reyes, Philip R Holland
Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses. While there is still a clear lack of understanding of its neurophysiology, it is beginning to be understood, and it seems to suggest migraine is a disorder of brain sensory processing, characterized by a generalized neuronal hyperexcitability...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916656/micrornas-as-biomarkers-for-early-breast-cancer-diagnosis-prognosis-and-therapy-prediction
#4
REVIEW
Farah J Nassar, Rihab Nasr, Rabih Talhouk
Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916655/allopurinol-as-a-therapeutic-option-in-cardiovascular-disease
#5
REVIEW
Osita N Okafor, K Farrington, Diana A Gorog
Epidemiological studies indicate that hyperuricaemia is an independent risk factor for cardiovascular disease. Alongside uric acid formation, increased xanthine oxidase activity also results in the formation of oxidative free radicals and superoxide particles. Oxidative stress significantly contributes to the development of cardiovascular disease, including endothelial cell dysfunction, atherosclerosis, vascular calcification and impaired myocardial energetics. Allopurinol, a competitive xanthine oxidase inhibitor, in addition to reducing serum uric acid levels, can act as a free radical scavenger...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916654/prion-like-mechanisms-and-potential-therapeutic-targets-in-neurodegenerative-disorders
#6
REVIEW
Masato Hasegawa, Takashi Nonaka, Masami Masuda-Suzukake
Prion-like propagation of abnormal intracytoplasmic proteins, which are the defining features of major neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), has been proposed. A growing body of evidence strongly suggests that abnormal tau, α-synuclein and TDP-43 have prion-like properties, convert the corresponding normal proteins into abnormal forms, and are transmitted from cell to cell, spreading throughout the brain. This idea is extremely important not only for understanding the pathogenesis and progression of these diseases, but also for the development of molecular therapies...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916653/pericytes-an-overlooked-player-in-vascular-pathobiology
#7
REVIEW
David Ferland-McCollough, Sadie Slater, Jai Richard, Carlotta Reni, Giuseppe Mangialardi
Pericytes are a heterogeneous population of cells located in the blood vessel wall. They were first identified in the 19(th) century by Rouget, however their biological role and potential for drug targeting have taken time to be recognised. Isolation of pericytes from several different tissues has allowed a better phenotypic and functional characterization. These findings revealed a tissue-specific, multi-functional group of cells with multilineage potential. Given this emerging evidence, pericytes have acquired specific roles in pathobiological events in vascular diseases...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916652/exploring-pericyte-and-cardiac-stem-cell-secretome-unveils-new-tactics-for-drug-discovery
#8
REVIEW
Georgina M Ellison-Hughes, Paolo Madeddu
Ischaemic diseases remain a major cause of morbidity and mortality despite continuous advancements in medical and interventional treatments. Moreover, available drugs reduce symptoms associated with tissue ischaemia, without providing a definitive repair. Cardiovascular regenerative medicine is an expanding field of research that aims to improve the treatment of ischaemic disorders through restorative methods, such as gene therapy, stem cell therapy, and tissue engineering. Stem cell transplantation has salutary effects through direct and indirect actions, the latter being attributable to growth factors and cytokines released by stem cells and influencing the endogenous mechanisms of repair...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916651/pharmacological-and-immunological-targeting-of-tumor-mesenchymalization
#9
REVIEW
Justin M David, Charli Dominguez, Claudia Palena
Controlling the spread of carcinoma cells to distant organs is the foremost challenge in cancer treatment, as metastatic disease is generally resistant to therapy and is ultimately incurable for the majority of patients. The plasticity of tumor cell phenotype, in which the behaviors and functions of individual tumor cells differ markedly depending upon intrinsic and extrinsic factors, is now known to be a central mechanism in cancer progression. Our expanding knowledge of epithelial and mesenchymal phenotypic states in tumor cells, and the dynamic nature of the transitions between these phenotypes has created new opportunities to intervene to better control the behavior of tumor cells...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916650/cardiac-oxidative-stress-in-diabetes-mechanisms-and-therapeutic-potential
#10
REVIEW
Alyssa Faria, Shanta J Persaud
Macrovascular complications of diabetes, including diabetic cardiovascular disease (CVD), occur through a number of hyperglycaemia-induced mechanisms that include generation of oxidative stress, accumulation of advanced glycation end-products (AGE) and activation of protein kinase C (PKC). Cardiac oxidative stress is associated with increased cardiac fibrosis and hypertrophy, and reduced cardiac performance and contractility, leading to severe cardiac dysfunction and potentially fatal cardiac events. It occurs under conditions of excessive synthesis of reactive oxygen species (ROS)...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916649/new-horizons-for-cystic-fibrosis-treatment
#11
REVIEW
Isabelle Fajac, Kris De Boeck
Cystic fibrosis is an inherited multi-system disease associated with chronic lung infection, malabsorption, salt loss syndromes, male infertility and leading to numerous comorbidities. The landscape in cystic fibrosis care has changed markedly with currently more adult patients than children in many countries. Over 2000 different mutations in theCFTRgene have been reported and the majority are extremely rare. Understanding howCFTRmutations translate to disturbed synthesis or function of the CFTR protein has opened the way to 'personalized' treatments to correct the basic defect...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916648/nav1-7-as-a-pain-target-from-gene-to-pharmacology
#12
REVIEW
Irina Vetter, Jennifer R Deuis, Alexander Mueller, Mathilde R Israel, Hana Starobova, Alan Zhang, Lachlan Rash, Mehdi Mobli
No abstract text is available yet for this article.
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27914981/complement-a-primer-for-the-coming-therapeutic-revolution
#13
REVIEW
Scott R Barnum
The complement system is an important part of the innate and adaptive immune systems. Originally characterized as a single serum component contributing to the killing of bacteria, we now know that there are close to sixty complement proteins, multiple activation pathways and a wide range of effector functions mediated by complement. The system plays a critical role in host defense against bacteria, viruses, fungi and other pathogens. However, inappropriate complement activation contributes to the pathophysiology of autoimmune diseases and many inflammatory syndromes...
November 30, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27908803/pericytes-integral-components-of-adult-hematopoietic-stem-cell-niches
#14
REVIEW
D Sá da Bandeira, J Casamitjana, M Crisan
The interest in perivascular cells as a niche for adult hematopoietic stem cells (HSCs) is significantly growing. In the adult bone marrow (BM), perivascular cells and HSCs cohabit. Among perivascular cells, pericytes are precursors of mesenchymal stem/stromal cells (MSCs) that are capable of differentiating into osteoblasts, adipocytes and chondrocytes. In situ, pericytes are recognised by their localisation to the abluminal side of the blood vessel wall, closely associated with endothelial cells in combination with the expression of markers such as CD146, neural glial 2 (NG2), platelet derived growth factor receptor β (PDGFRβ), α-smooth muscle actin (α-SMA), nestin (Nes) and/or leptin receptor (LepR)...
November 28, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27902931/human-presynaptic-receptors
#15
REVIEW
Eberhard Schlicker, Thomas Feuerstein
Presynaptic receptors are sites at which transmitters, locally formed mediators or hormones inhibit or facilitate the release of a given transmitter from its axon terminals. The interest in the identification of presynaptic receptors has faded in recent years and it may therefore be justified to give an overview of their occurrence in the autonomic and central nervous system; this review will focus on presynaptic receptors in human tissues. Autoreceptors are presynaptic receptors at which a given transmitter restrains its further release, though in some instances may also increase its release...
November 27, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27902930/modulating-micrornas-in-cardiac-surgery-patients-novel-therapeutic-opportunities
#16
REVIEW
Giovanni Biglino, Massimo Caputo, Cha Rajakaruna, Gianni Angelini, Eva van Rooij, Costanza Emanueli
This review focuses on microRNAs (miRs) in cardiac surgery, where they are emerging as potential targets for therapeutic intervention as well as novel clinical biomarkers. Identification of the up/down-regulation of specific miRs in defined groups of cardiac surgery patients can lead to the development of novel strategies for targeted treatment in order to maximise therapeutic results and minimise acute, delayed or chronic complications. MiRs could also be involved in determining the outcome independently of complications, for example in relation to myocardial perfusion and fibrosis...
November 27, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27889330/use-of-biologics-to-treat-acute-exacerbations-and-manage-disease-in-asthma-copd-and-ipf
#17
REVIEW
Lynne A Murray, Chris Grainge, Peter A Wark, Darryl A Knight
A common feature of chronic respiratory disease is the progressive decline in lung function. The decline can be indolent, or it can be accelerated by acute exacerbations, whereby the patient experiences a pronounced worsening of disease symptoms. Moreover, acute exacerbations may also be a marker of insufficient disease management. The underlying cause of an acute exacerbation can be due to insults such as pathogens or environmental pollutants, or the cause can be unknown. For each acute exacerbation, the patient may require medical intervention such as rescue medication, or in more severe cases, hospitalization and ventilation and have an increased risk of death...
November 24, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27889329/perivascular-cells-and-tissue-engineering-current-applications-and-untapped-potential
#18
REVIEW
Elisa Avolio, Valeria V Alvino, Mohamed T Ghorbel, Paola Campagnolo
The recent development of tissue engineering provides exciting new perspectives for the replacement of failing organs and the repair of damaged tissues. Perivascular cells, including vascular smooth muscle cells, pericytes and other tissue specific populations residing around blood vessels, have been isolated from many organs and are known to participate to the in situ repair process and angiogenesis. Their potential has been harnessed for cell therapy of numerous pathologies; however, in this Review we will discuss the potential of perivascular cells in the development of tissue engineering solutions for healthcare...
November 23, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27865998/intensive-ldl-cholesterol-lowering-therapy-and-neurocognitive-function
#19
REVIEW
Maciej Banach, Manfredi Rizzo, Dragana Nikolic, George Howard, VirginiaJ Howard, DimitriP Mikhailidis
The key lipid-lowering target is to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new treatment strategies for lipid-lowering therapy include using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to reduce residual risk of cardiovascular diseases (CVD). However, concerns about possible adverse effects, including neurocognitive disorders, were issued by the Food and Drug Administration (FDA). The current disputable evidence does not allow definite conclusions as to whether statins contribute to, or cause, clinically meaningful cognitive impairment...
November 16, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27777088/il-15-receptor-alpha-as-the-magic-wand-to-boost-the-success-of-il-15-antitumor-therapies-the-upswing-of-il-15-transpresentation
#20
Johan Mj Van den Bergh, Eva Lion, Viggo Fi Van Tendeloo, Evelien Ljm Smits
Interleukin (IL)-15 as a stand-alone therapy can activate the antitumor functions of immune effector cells resulting in significant tumor regression. Interestingly, combining IL-15 with the α-moiety of its receptor (IL-15Rα), also called IL-15 transpresentation, increases the in vivo half-life of IL-15 and enhances binding of IL-15 with cells expressing the IL-15Rβγ, such as NK cells and CD8(+) T cells. These features enlarge the signal transmission of IL-15, resulting in improved proliferation and antitumor activities of both NK cells and CD8(+) T cells, eventually leading to enhanced killing of tumor cells...
October 21, 2016: Pharmacology & Therapeutics
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