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Current Opinion in Pharmacology

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https://www.readbyqxmd.com/read/27889687/role-of-inflammation-in-obesity-related-breast-cancer
#1
REVIEW
Elisa Crespi, Giulia Bottai, Libero Santarpia
Chronic inflammation associated with obesity is now recognized to be an important condition in promoting carcinogenesis and progression in breast cancer patients, mostly in postmenopausal women with tumors expressing estrogen and progesterone receptors. In obese patients, altered levels of several inflammatory mediators regulating aromatase and estrogen expression are one of the mechanisms responsible of increase breast cancer risk. Growing attention has also been paid to the local adipose inflammation and the role played by macrophages as determinants of breast cancer risk recurrence and prognosis...
November 24, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27886642/obesity-and-the-breast-cancer-methylome
#2
REVIEW
William B Coleman
Breast cancer is associated with risk factors such as advancing age and obesity. However, the linkages between these risk factors for breast cancer development and initiation of the disease are not yet clear. Obesity may drive breast cancer development through increases in circulating estrogens in postmenopausal women. Mammary cell susceptibility to neoplastic transformation requires both genetic and epigenetic alterations, including changes in DNA methylation. Obesity is also subject to epigenetic regulation...
November 22, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27883943/targeted-therapy-for-breast-cancer-and-molecular-mechanisms-of-resistance-to-treatment
#3
REVIEW
Guowei Gu, Derek Dustin, Suzanne Aw Fuqua
In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown several targetable pathways that overcome resistance in the clinical setting...
November 21, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27875804/optogenetic-approaches-for-dissecting-neuromodulation-and-gpcr-signaling-in-neural-circuits
#4
REVIEW
Skylar M Spangler, Michael R Bruchas
Optogenetics has revolutionized neuroscience by providing means to control cell signaling with spatiotemporal control in discrete cell types. In this review, we summarize four major classes of optical tools to manipulate neuromodulatory GPCR signaling: opsins (including engineered chimeric receptors); photoactivatable proteins; photopharmacology through caging-photoswitchable molecules; fluorescent protein based reporters and biosensors. Additionally, we highlight technologies to utilize these tools in vitro and in vivo, including Cre dependent viral vector expression and two-photon microscopy...
November 19, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27875786/inflammation-dysregulated-metabolism-and-aromatase-in-obesity-and-breast-cancer
#5
REVIEW
Heba Zahid, Evan R Simpson, Kristy A Brown
Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat...
November 19, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27876260/editorial-overview-endocrine-and-metabolic-diseases-adipocyte-dysfunction-fuels-signalings-for-breast-cancer-progression
#6
EDITORIAL
Sebastiano Andò
No abstract text is available yet for this article.
November 18, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27842256/neurobiological-insights-and-novel-therapeutic-opportunities-for-cns-disorders-from-mglu-receptor-allosteric-and-biased-modulation
#7
REVIEW
Shane Hellyer, Katie Leach, Karen J Gregory
The metabotropic glutamate (mGlu) receptor family is a potential therapeutic target for multiple central nervous system (CNS) disorders. However, aspects of mGlu receptor signaling and their role in neural pathways remain to be fully elucidated. Novel subtype selective allosteric modulators have revealed new roles for mGlu receptors in brain health and disease, as well as expanding on previously underappreciated aspects of mGlu signaling such as biased agonism and modulation. Recent advances have improved our understanding of mGlu receptor function...
November 11, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27838588/diversity-and-bias-through-dopamine-d2r-heteroreceptor-complexes
#8
REVIEW
Dasiel O Borroto-Escuela, Kjell Fuxe
The D2R is a hub receptor interacting with a large number of other GPCRs. A2AR activation of the antagonistic A2AR-D2R interaction not only leads to inhibition of the Gi/o signaling but also to an increase in β-arrestin2 signaling over the D2R protomer. Hallucinogenic 5-HT2AR agonists can produce a biased agonist state at the 5-HT2AR protomer of D2R-5-HT2AR heteroreceptor complexes with increased D2R recognition and Gi/o mediated signaling. Allosteric receptor-receptor interactions in D2-NTR1 heteroreceptor complexes inhibit D2R function and can switch G protein coupling...
November 10, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27837687/measuring-g-protein-coupled-receptor-signalling-in-the-brain-with-resonance-energy-transfer-based-biosensors
#9
REVIEW
Jace Jones-Tabah, Paul Bs Clarke, Terence E Hébert
Activation of a G protein-coupled receptor (GPCR) triggers downstream signalling pathways whose identity is determined not only by the genetic background of the cell, but also by the interacting ligand. Assays that measure endogenous GPCR signalling in vivo are needed to specify the intracellular signalling pathways leading to therapeutic vs. adverse outcomes in animal models. To this end, genetically encoded biosensors can be expressed in vivo with cell type specificity to report GPCR signalling in real time...
November 9, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27835801/cannabinoid-receptor-ligand-bias-implications-in-the-central-nervous-system
#10
REVIEW
Robert B Laprairie, Amina M Bagher, Eileen M Denovan-Wright
The G protein-coupled cannabinoid receptors CB1, CB2, GPR18, and GPR55 regulate neurotransmission, pain, and inflammation and have been intensively investigated as potential drug targets. Each of these GPCRs is coupled to multiple effector proteins mediating divergent cellular signals. The ligand bias of cannabinoid-targeted compounds is only beginning to be quantified. Research into cannabinoid bias is now revealing correlations between bias in cell culture and functional outcomes in vivo. We present an example study of cannabinoid bias in the context of Huntington disease...
November 8, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27835800/contribution-of-heteromerization-to-g-protein-coupled-receptor-function
#11
REVIEW
Supriya A Gaitonde, Javier González-Maeso
G protein-coupled receptors (GPCRs) are a remarkably multifaceted family of transmembrane proteins that exert a variety of physiological effects. Although family A GPCRs are able to operate as monomers, there is increasing evidence that heteromerization represents a fundamental aspect of receptor function, trafficking and pharmacology. Most recently, it has been suggested that GPCR heteromers may play a crucial role as new molecular targets of heteromer-selective and bivalent ligands. The current review summarizes key recent developments in these topics...
November 8, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27816025/leptin-obesity-and-breast-cancer-progress-to-understanding-the-molecular-connections
#12
REVIEW
Ines Barone, Cinzia Giordano, Daniela Bonofiglio, Sebastiano Andò, Stefania Catalano
Obesity has a complicated connection to both breast cancer risk and the clinical behaviour of the established disease. The obese setting provides a unique adipose tissue microenvironment that, in association with systemic endocrine modifications, promotes tumor initiation, primary growth, invasion, and metastatic progression. This review presents an overview of the clinical and experimental evidences highlighting the adipokine leptin as the most important molecular mediator of obesity-breast cancer axis. The research of leptin network operating in this context could launch a new field not only in the knowledge of risk factors for breast cancer but also in the development of leptin targeting drugs as promising anticancer agents...
November 2, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27835802/transient-receptor-potential-channels-in-neuropathic-pain
#13
REVIEW
Lilian Basso, Christophe Altier
Neuropathic pain caused by disease or dysfunction of the nervous system is one of the most difficult pain conditions to treat. Symptoms include a hypersensitivity to mechanical and thermal stimuli, processed by specialized nociceptors that constitute the first line of defence of the somatosensory system. The detection of these stimuli depends on the TRP ion channel family, which activates upon damaging pressure, extreme temperature, or toxic endogenous and exogenous chemicals. This review will summarize the current knowledge of the contribution of TRP channels, particularly the thermosensitive TRP, including TRPV1, TRPA1 and TRPM8 channels that play a central role in the sensitization of nociceptive transduction...
October 27, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27768908/regulation-of-voltage-gated-calcium-channels-by-gpcrs-and-post-translational-modification
#14
Junting Huang, Gerald W Zamponi
Calcium entry via voltage gated calcium channels mediates a wide range of physiological functions, whereas calcium channel dysregulation has been associated with numerous pathophysiological conditions. There are myriad cell signaling pathways that act on voltage gated calcium channels to fine tune their activities and to regulate their cell surface expression. These regulatory mechanisms include the activation of G protein-coupled receptors and downstream phosphorylation events, and their control over calcium channel trafficking through direct physical interactions...
October 18, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27750091/hedgehog-signaling-in-the-stomach
#15
Daniel Konstantinou, Nina Bertaux-Skeirik, Yana Zavros
The Hedgehog (Hh) signaling pathway not only plays a key part in controlling embryonic development, but in the adult stomach governs important cellular events such as epithelial cell differentiation, proliferation, gastric disease, and regeneration. In particular, Sonic Hedgehog (Shh) signaling has been well studied for its role in gastric physiology and pathophysiology. Shh is secreted from the gastric parietal cells and contributes to the regeneration of the epithelium in response to injury, or the development of gastritis during Helicobacter pylori infection...
October 14, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27745842/editorial-overview-gastrointestinal-gut-hormones-from-bench-to-bedside
#16
Graham J Dockray, Andrea Varro
No abstract text is available yet for this article.
October 10, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27710813/potential-clinical-indications-for-a-cck2-receptor-antagonist
#17
Malcolm Boyce, Katie A Lloyd, D Mark Pritchard
Gastrin controls gastric acid secretion and mucosal cell growth, especially of enterochromaffin-like cells, via gastrin/cholecystokinin-2 receptor (CCK2R) binding and downstream signalling. Studies in animal models, healthy subjects and patients with gastric neuroendocrine tumours provide compelling evidence to justify developing a CCK2R antagonist (CCK2RA) for preventing or treating the trophic effects of hypergastrinaemia or conditions expressing CCK2R, and with or without a proton pump inhibitor, for treating gastric acid-related conditions...
October 3, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27707534/corrigendum-to-chronic-hepatitis-b-immune-pathogenesis-and-emerging-immunotherapeutics-curr-opin-pharmacol-30-2016-93-105
#18
Kyong-Mi Chang, Mengfei Liu
No abstract text is available yet for this article.
October 1, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27643666/gut-hormone-gpcrs-structure-function-drug-discovery
#19
Arnau Cordomí, Daniel Fourmy, Irina G Tikhonova
Crystallization and determination of the high resolution three-dimensional structure of the β2-adrenergic receptor in 2007 was followed by structure elucidation of a number of other receptors, including those for neurotensin and glucagon. These major advances foster the understanding of structure-activity relationship of these receptors and structure-based rational design of new ligands having more predictable activity. At present, structure determination of gut hormone receptors in complex with their ligands (natural, synthetic) and interacting signalling proteins, for example, G-proteins, arrestins, represents a challenge which promises to revolutionize gut hormone endocrinonology...
September 16, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27639371/antiviral-strategies-to-eliminate-hepatitis-b-virus-covalently-closed-circular-dna-cccdna
#20
Peter Revill, Stephen Locarnini
It has been over 50 years since the discovery of hepatitis B virus (HBV), yet 240 million people worldwide live with chronic HBV, resulting in up to 800000 deaths per year. A cure is yet to be achieved, due largely to a viral nuclear reservoir of transcriptionally active covalently closed circular DNA (cccDNA). While current antiviral therapies are effective at reducing viral replication, they have no impact on the existing cccDNA reservoir. Identifying mechanisms to either eliminate (complete cure) or inactivate (functional cure) HBV cccDNA are a major focus of HBV research worldwide...
September 15, 2016: Current Opinion in Pharmacology
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