TSH/IGF1 receptor crosstalk: Mechanism and clinical implications
Publication date: Available online 13 February 2020Source: Pharmacology & TherapeuticsAuthor(s): Christine C. Krieger, Susanne Neumann, Marvin C. GershengornAbstractIncreasing evidence of interdependence between G protein-coupled receptors and receptor tyrosine kinase signaling pathways has prompted reevaluation of crosstalk between these receptors in disease and therapy. Investigations into thyroid-stimulating hormone (TSH) and insulin-like growth factor 1 (IGF1) receptor crosstalk, and its application to the clinic have in particular shown recent progress. In this review, we summarize current insights into the mechan...
Source: Pharmacology and Therapeutics - February 15, 2020 Category: Drugs & Pharmacology Source Type: research

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions
Publication date: Available online 14 February 2020Source: Pharmacology & TherapeuticsAuthor(s): Shiying Shao, QinQin Xu, Xuefeng Yu, Ruping Pan, Yong ChenAbstractDipeptidyl peptidase 4 (DPP4) inhibitors (DPP4is) are oral anti-diabetic drugs (OADs) for the treatment of type 2 diabetes mellitus (T2DM) through inhibiting the degradation of incretin peptides. Numerous investigations have been focused on the effects of DPP4is on glucose homeostasis. However, there are limited evidences demonstrating their Potential modulatory functions in the immune system. DPP4, originally known as the lymphocyte cell surface protein CD26...
Source: Pharmacology and Therapeutics - February 15, 2020 Category: Drugs & Pharmacology Source Type: research

Recent advances in genome editing of stem cells for drug discovery and therapeutic application
Publication date: Available online 12 February 2020Source: Pharmacology & TherapeuticsAuthor(s): Jaesuk Lee, Delger Bayarsaikhan, Govigerel Bayarsaikhan, Jin-Soo Kim, Elizabeth Schwarzbach, Bonghee LeeAbstractGenome engineering technologies right from viral vector-mediated to protein-based editing— which include zinc finger nucleases, TALENs, and CRISPR/Cas systems—have been improved significantly. These technologies have facilitated drug discovery and have resulted in the development of potential curative therapies for many intractable diseases. They can efficiently correct genetic errors; however, these t...
Source: Pharmacology and Therapeutics - February 13, 2020 Category: Drugs & Pharmacology Source Type: research

Targeting defective pulmonary innate immunity – A new therapeutic option?
Publication date: Available online 13 February 2020Source: Pharmacology & TherapeuticsAuthor(s): Kylie B.R. Belchamber, Louise E. DonnellyAbstractChronic pulmonary conditions now account for 1 in 15 deaths in the US and mortality is increasing. Chronic obstructive pulmonary disease (COPD) is due to become the 3rd largest cause of mortality by 2030 and mortality from other respiratory conditions such as asthma, idiopathic pulmonary fibrosis and cystic fibrosis are not reducing. There is an urgent need for novel therapies to address this problem as many of the current strategies targeting inflammation are not sufficient....
Source: Pharmacology and Therapeutics - February 13, 2020 Category: Drugs & Pharmacology Source Type: research

Cannabinoids in the descending pain modulatory circuit: Role in inflammation
Publication date: Available online 29 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Courtney A. Bouchet, Susan L. IngramAbstractThe legalization of cannabis in some states has intensified interest in the potential for cannabis and its constituents to lead to novel therapeutics for pain. Our understanding of the cellular mechanisms underlying cannabinoid actions in the brain have lagged behind opioids; however, the current opioid epidemic has also increased attention on the use of cannabinoids as alternatives to opioids for pain, especially chronic pain that requires long-term use. Endogenous cannabinoids ar...
Source: Pharmacology and Therapeutics - January 29, 2020 Category: Drugs & Pharmacology Source Type: research

Berberine in the treatment of metabolism-related chronic diseases: A drug cloud (dCloud) effect to target multifactorial disorders
Publication date: Available online 27 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Wei-Jia Kong, Claudio Vernierib, Marco Foiani, Jian-Dong JiangAbstractBerberine (BBR) is a multi-target drug (MTD) that has proven effective in the treatment of metabolism-related chronic diseases (CDs). However, the mode of action (MOA) of BBR remains to be clarified. At a cellular level, the inhibitory effect of BBR on mitochondrial enzymes is probably responsible for many of its biological activities, including the activation of low-density lipoprotein receptor (LDLR), AMP-activated protein kinase (AMPK) and insulin recep...
Source: Pharmacology and Therapeutics - January 28, 2020 Category: Drugs & Pharmacology Source Type: research

A BAG's life: Every connection matters in cancer
Publication date: Available online 27 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Elena Mariotto, Giampietro Viola, Carlo Zanon, Sanja AveicAbstractThe members of the BCL-2 associated athanogene (BAG) family participate in the regulation of a variety of interrelated physiological processes, such as autophagy, apoptosis, and protein homeostasis. Under normal circumstances, the six BAG members described in mammals (BAG1-6) principally assist the 70 kDa heat-shock protein (HSP70) in protein folding; however, their role as oncogenes is becoming increasingly evident. Deregulation of the BAG multigene family ...
Source: Pharmacology and Therapeutics - January 28, 2020 Category: Drugs & Pharmacology Source Type: research

Role of Rad51 and DNA repair in cancer: A molecular perspective
Publication date: Available online 27 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Erik Laurini, Domenico Marson, Alice Fermeglia, Suzana Aulic, Maurizio Fermeglia, Sabrina PriclAbstractThe maintenance of genome integrity is essential for any organism survival and for the inheritance of traits to offspring. To the purpose, cells have developed a complex DNA repair system to defend the genetic information against both endogenous and exogenous sources of damage. Accordingly, multiple repair pathways can be aroused from the diverse forms of DNA lesions, which can be effective per se or via crosstalk with othe...
Source: Pharmacology and Therapeutics - January 28, 2020 Category: Drugs & Pharmacology Source Type: research

TRPC channels: Structure, function, regulation and recent advances in small molecular probes
Publication date: Available online 28 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Hongbo Wang, Xiaoding Cheng, Jinbin Tian, Yuling Xiao, Tian Tian, Fuchun Xu, Xuechuan Hong, Michael X. ZhuAbstractTransient receptor potential canonical (TRPC) channels constitute a group of receptor-operated calcium-permeable nonselective cation channels of the TRP superfamily. The seven mammalian TRPC members, which can be further divided into four subgroups (TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7) based on their amino acid sequences and functional similarities, contribute to a broad spectrum of cellular functions and physio...
Source: Pharmacology and Therapeutics - January 28, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: February 2020Source: Pharmacology & Therapeutics, Volume 206Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - January 28, 2020 Category: Drugs & Pharmacology Source Type: research

Pharmacology and perspectives in erectile dysfunction in man
Publication date: Available online 25 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Emma Mitidieri, Giuseppe Cirino, Roberta d’Emmanuele di Villa Bianca, Raffaella SorrentinoAbstractPenile erection is a perfect example of microcirculation modulated by psychological factors and hormonal status. It is the result of a complex neurovascular process that involves the integrative synchronized action of vascular endothelium; smooth muscle; and psychological, neuronal, and hormonal systems. Therefore, the fine coordination of these events is essential to maintain penile flaccidity or allow erection; an altera...
Source: Pharmacology and Therapeutics - January 26, 2020 Category: Drugs & Pharmacology Source Type: research

A hypothesis of monoamine (5-HT) – Glutamate/GABA long neural circuit: Aiming for fast-onset antidepressant discovery
Publication date: Available online 25 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Yun-Feng LiAbstractMajor depressive disorder has become a global public health problem of serious concern. Most of the clinical antidepressants are developed under the classic “monoamine hypothesis (strategy)”. These drugs generally have such deficiencies including slow onset and limited efficiency, cognitive impairment and suicidal tendency. Therefore, it is the direction to break through the classic monoamine strategy framework for developing antidepressants that have fast-acting, lower side effects, and cognit...
Source: Pharmacology and Therapeutics - January 26, 2020 Category: Drugs & Pharmacology Source Type: research

Make your best BET: The emerging role of BET inhibitor treatment in malignant tumors
Publication date: Available online 11 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Oliver Bechter, Patrick SchöffskiAbstractBromodomains are protein-protein interaction modules with a great diversity in terms of number of proteins and their function. The bromodomain and extraterminal protein (BET) represents a distinct subclass of bromodomain proteins mainly involved in transcriptional regulation via their interaction with acetylated chromatin. In cancer cells BET proteins are found to be altered in many ways such as overexpression, mutations and fusions of BET proteins or their interference with canc...
Source: Pharmacology and Therapeutics - January 22, 2020 Category: Drugs & Pharmacology Source Type: research

Natural products-based polypharmacological modulation of the peripheral immune system for the treatment of neuropsychiatric disorders
Publication date: Available online 21 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Simon Wing-Fai Mok, Vincent Kam-Wai Wong, Hang-Hong Lo, Ivo Ricardo de Seabra Rodrigues Dias, Elaine Lai-Han Leung, Betty Yuen-Kwan Law, Liang LiuAbstractChronic inflammation of the central nervous system (CNS) is critical to the pathogenesis of neuropsychiatric disorders (NPDs) that affect the global population. Current therapeutics for NPDs are limited to relieving symptoms and induce many adverse effects. Therefore, the discovery of novel therapeutic agents from natural sources is urgently needed. Intriguingly, the immune...
Source: Pharmacology and Therapeutics - January 21, 2020 Category: Drugs & Pharmacology Source Type: research

Antifungal effects of statins
In this study, we reviewed in-vitro and in-vivo studies, as well as clinical reports pertaining to the antifungal efficacy of statins. In addition, we have addressed various modulators of statin anti-fungal activity and the potential mechanisms responsible for their anti-fungal effects. In general, statins do possess anti-fungal activity, targeting a broad spectrum of fungal organisms including human opportunistic pathogens such as Candida spp. and Zygomycetes, Dermatophytes, alimentary toxigenic species such as Aspergillus spp., and fungi found in device implants such as Saccharomyces cerevisiae. Statins have been shown t...
Source: Pharmacology and Therapeutics - January 16, 2020 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: January 2020Source: Pharmacology & Therapeutics, Volume 205Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - January 15, 2020 Category: Drugs & Pharmacology Source Type: research

Immunotherapy in sepsis - brake or accelerate?
This article reviews recent and ongoing clinical investigations using immunostimulatory or immunosuppressive therapies against sepsis including non-pharmacological and novel preclinical approaches. (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - January 12, 2020 Category: Drugs & Pharmacology Source Type: research

In situ imaging of monoamine localization and dynamics
Publication date: Available online 10 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Eiji Sugiyama, Ashwin N. Skelly, Makoto Suematsu, Yuki SugiuraAbstractRecent advances in sample preparation protocols and instrumentation allow current imaging mass spectrometry (IMS) to enable the visualization of small molecule tissue localization, including that of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine. Although monoamine-producing neurons, and their projections and synaptic connections, have been thoroughly characterized, in situ monoamine localization within these circuits remains ...
Source: Pharmacology and Therapeutics - January 12, 2020 Category: Drugs & Pharmacology Source Type: research

Make your best BET the emerging role of BET inhibitor treatment in malignant tumors
Publication date: Available online 11 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Oliver Bechter, Patrick SchöffskiAbstractBromodomains are protein-protein interaction modules with a great diversity in terms of number of proteins and their function. The bromodomain and extraterminal protein (BET) represents a distinct subclass of bromodomain proteins mainly involved in transcriptional regulation via their interaction with acetylated chromatin. In cancer cells BET proteins are found to be altered in many ways such as overexpression, mutations and fusions of BET proteins or their interference with canc...
Source: Pharmacology and Therapeutics - January 12, 2020 Category: Drugs & Pharmacology Source Type: research

Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis
Publication date: Available online 9 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Andras Garami, Yury P. Shimansky, Zoltan Rumbus, Robson C.L. Vizin, Nelli Farkas, Judit Hegyi, Zsolt Szakacs, Margit Solymar, Alexandra Csenkey, Dan A. Chiche, Ram Kapil, Donald J. Kyle, Wade D. Van Horn, Peter Hegyi, Andrej A. RomanovskyAbstractAntagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (Tb) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and ...
Source: Pharmacology and Therapeutics - January 10, 2020 Category: Drugs & Pharmacology Source Type: research

Recent advances in bone-targeted therapy
Publication date: Available online 8 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Chen Shi, Tingting Wu, Yu He, Yu Zhang, Dehao FuAbstractThe coordination between bone resorption and bone formation plays an essential role in keeping the mass and microstructure integrity of the bone in a steady state. However, this balance can be disturbed in many pathological conditions of the bone. Nowadays, the classical modalities for treating bone-related disorders are being challenged by severe obstacles owing to low tissue selectivity and considerable safety concerns. Moreover, as a highly mineralized tissue, the bon...
Source: Pharmacology and Therapeutics - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

The therapeutic potential of second and third generation CB1R antagonists
Publication date: Available online 9 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Resat Cinar, Malliga R. Iyer, George KunosAbstractEndocannabinoids acting via CB1 receptors (CB1R) play a critical role in regulating energy homeostasis, which was the rationale for the pharmaceutical development of CB1R antagonists for the treatment of obesity. Although the first-in-class CB1R antagonist rimonabant proved to be effective in mitigating obesity and its multiple cardiometabolic complications, it was withdrawn from clinical use due to CNS-mediated neuropsychiatric side effects, which halted the further therapeut...
Source: Pharmacology and Therapeutics - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Cyclic nucleotide phosphodiesterases: New targets in the metabolic syndrome?
Publication date: Available online 9 January 2020Source: Pharmacology & TherapeuticsAuthor(s): Claire Lugnier, Alain Meyer, Samy Talha, Bernard GenyAbstractMetabolic diseases have a tremendous impact on human morbidity and mortality. Numerous targets regulating adenosine monophosphate kinase (AMPK) have been identified for treating the metabolic syndrome (MetS), and many compounds are being used or developed to increase AMPK activity. In parallel, the cyclic nucleotide phosphodiesterase families (PDEs) have emerged as new therapeutic targets in cardiovascular diseases, as well as in non-resolved pathologies. Since some...
Source: Pharmacology and Therapeutics - January 9, 2020 Category: Drugs & Pharmacology Source Type: research

Therapeutic potential of targeting mixed lineage kinases in cancer and inflammation
Publication date: Available online 18 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Kathleen A. Gallo, Edmund Ellsworth, Hayden Stoub, Susan E. ConradAbstractDysregulation of intracellular signaling pathways is a key attribute of diseases associated with chronic inflammation, including cancer. Mitogen activated protein kinases have emerged as critical conduits of intracellular signal transmission, yet due to their ubiquitous roles in cellular processes, their direct inhibition may lead to undesired effects, thus limiting their usefulness as therapeutic targets. Mixed lineage kinases (MLKs) are mitogen-acti...
Source: Pharmacology and Therapeutics - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Lipid-modifying therapy in chronic kidney disease: Pathophysiological and clinical considerations
Publication date: Available online 18 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Gunnar H. Heine, Kathrin Eller, Julia T. Stadler, Kyrill S. Rogacev, Gunther MarscheAbstractChronic kidney disease (CKD), which affects>10% of the population worldwide, is associated with a dramatically increased rate of cardiovascular disease (CVD). More people with CKD will die from CVD than develop end-stage renal disease with dialysis-dependency. However, the contribution of classical atherosclerotic cardiovascular risk factors is less evident than in the general population. Particularly, the relationship between dys...
Source: Pharmacology and Therapeutics - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Circulating tumor DNA as an early cancer detection tool
Publication date: Available online 18 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Andrea Campos-Carrillo, Jeffrey N. Weitzel, Prativa Sahoo, Russell Rockne, Janet V. Mokhnatkin, Muhammed Murtaza, Stacy W. Gray, Laura Goetz, Ajay Goel, Nicholas Schork, Thomas P. SlavinAbstractCirculating tumor DNA holds substantial promise as an early detection biomarker, particularly for cancers that do not have currently accepted screening methodologies, such as ovarian, pancreatic, and gastric cancers. Many features intrinsic to ctDNA analysis may be leveraged to enhance its use as an early cancer detection biomarker: ...
Source: Pharmacology and Therapeutics - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Sphingosine kinase and sphingosine-1-phosphate receptor signaling pathway in inflammatory gastrointestinal disease and cancers: A novel therapeutic target
Publication date: Available online 18 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Olga A. Sukocheva, Hideki Furuya, Mei Li Ng, Markus Friedemann, Mario Menschikowski, Vadim V. Tarasov, Vladimir N. Chubarev, Sergey G. Klochkov, Margarita E. Neganova, Arduino A. Mangoni, Gjumrakch Aliev, Anupam BishayeeAbstractInflammatory gastrointestinal (GI) diseases and malignancies are associated with growing morbidity and cancer-related mortality worldwide. GI tumor and inflammatory cells contain activated sphingolipid-metabolizing enzymes, including sphingosine kinase 1 (SphK1) and SphK2, that generate sphingosine-1...
Source: Pharmacology and Therapeutics - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

The past, present and future perspectives of matrix metalloproteinase inhibitors
Publication date: Available online 18 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Kang Li, Franklin R. Tay, Cynthia Kar Yung YiuAbstractMatrix metalloproteinases (MMPs) are a large family of enzymes that degrade the extracellular matrix (ECM). Under pathologic conditions, overexpression of MMPs or insufficient control by tissue inhibitors of MMPs (TIMPs) results in the dysregulation of tissue remodeling and causes a variety of diseases such as encephalomyelitis, rheumatoid arthritis, Alzheimer's disease and tumors. Therefore, the high affinity of MMPs for biomolecules renders them attractive targets for ...
Source: Pharmacology and Therapeutics - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Metal homeostasis disturbances in neurodegenerative disorders, with special emphasis on Creutzfeldt-Jakob disease – Potential pathogenetic mechanism and therapeutic implications
Publication date: Available online 19 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Yutaka Nakagawa, Shizuo YamadaAbstractCreutzfeldt-Jakob disease (CJD) is characterized by a rapidly progressive dementia often accompanied by myoclonus and other signs of brain dysfunction, relying on the conversion of the normal cellular form of the prion protein (PrPC) to a misfolded form (PrPSc). The neuropathological changes include spongiform degeneration, neuronal loss, astrogliosis, and deposition of PrPSc. It is still unclear how these pathological changes correlate with the development of CJD symptoms because few p...
Source: Pharmacology and Therapeutics - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Cancer immunotherapy with immunoadjuvants, nanoparticles, and checkpoint inhibitors: Recent progress and challenges in treatment and tracking response to immunotherapy
Publication date: Available online 19 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Michael-Joseph Gorbet, Ashish RanjanAbstractChemotherapy, surgery, and radiation are accepted as the preferred treatment modalities against cancer, but in recent years the use of immunotherapeutic approaches has gained prominence as the fourth treatment modality in cancer patients. In this approach, a patient’s innate and adaptive immune systems are activated to achieve clearance of occult cancerous cells. In this review, we discuss the preclinical and clinical immunotherapeutic (e.g., immunoadjuvants (in-situ vaccine...
Source: Pharmacology and Therapeutics - December 19, 2019 Category: Drugs & Pharmacology Source Type: research

Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony
Publication date: Available online 10 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Lingling Zhang, Wei WeiAbstractAs a Traditional Chinese Medicine, Paeonia lactiflora Pallas has been used to treat pain, inflammation and immune disorders for more than 1000 years in China. Total glycoside of paeony (TGP) is extracted from the dried root of Paeonia lactiflora Pallas. Paeoniflorin (Pae) is the major active component of TGP. Our research group has done a lot of work in the pharmacological mechanisms of Pae and found that Pae possessed extensive anti-inflammatory and immune regulatory effects. Pae could inhi...
Source: Pharmacology and Therapeutics - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Lactate/GPR81 signaling and proton motive force in cancer: Role in angiogenesis, immune escape, nutrition, and Warburg phenomenon
Publication date: Available online 10 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Timothy Brown, Vadivel GanapathyAbstractReprogramming of biochemical pathways is a hallmark of cancer cells, and generation of lactic acid from glucose/glutamine represents one of the consequences of such metabolic alterations. Cancer cells export lactic acid out to prevent intracellular acidification, not only increasing lactate levels but also creating an acidic pH in extracellular milieu. Lactate and protons in tumor microenvironment are not innocuous bystander metabolites but have special roles in promoting tumor-cell p...
Source: Pharmacology and Therapeutics - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Time-dependent enzyme inactivation: Numerical analyses of in vitro data and prediction of drug-drug interactions
Publication date: Available online 11 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Jaydeep Yadav, Erickson Paragas, Ken Korzekwa, Swati NagarAbstractCytochrome P450 (CYP) enzyme kinetics often do not conform to Michaelis-Menten assumptions, and time-dependent inactivation (TDI) of CYPs displays complexities such as multiple substrate binding, partial inactivation, quasi-irreversible inactivation, and sequential metabolism. Additionally, in vitro experimental issues such as lipid partitioning, enzyme concentrations, and inactivator depletion can further complicate the parameterization of in vitro TDI. The ...
Source: Pharmacology and Therapeutics - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Current perspectives on targeting PIM kinases to overcome mechanisms of drug resistance and immune evasion in cancer
Publication date: Available online 11 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Tom Malone, Lea Schӓfer, Nathalie Simon, Susan Heavey, Sinead Cuffe, Stephen Finn, Gillian Moore, Kathy GatelyAbstractPIM kinases are a class of serine/threonine kinases that play a role in several of the hallmarks of cancer including cell cycle progression, metabolism, inflammation and immune evasion. Their constitutively active nature and unique catalytic structure has led them to be an attractive anticancer target through the use of small molecule inhibitors. This review highlights the enhanced activity of PIM kinases i...
Source: Pharmacology and Therapeutics - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Unraveling cancer lineage drivers in squamous cell carcinomas
Publication date: Available online 11 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Yinglu Guan, Guan Wang, Danielle Fails, Priyadharsini Nagarajan, Yejing GeAbstractCancer hijacks embryonic development and adult wound repair mechanisms to fuel malignancy. Cancer frequently originates from de-regulated adult stem cells or progenitors, which are otherwise essential units for postnatal tissue remodeling and repair. Cancer genomics studies have revealed convergence of multiple cancers across organ sites, including squamous cell carcinomas (SCCs), a common group of cancers arising from the head and neck, esoph...
Source: Pharmacology and Therapeutics - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Targeting ATR as Cancer Therapy: A new era for synthetic lethality and synergistic combinations?
Publication date: Available online 11 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Alice Bradbury, Sally Hall, Nicola Curtin, Yvette DrewAbstractThe DNA damage response (DDR) machinery is responsible for detecting DNA damage, pausing the cell cycle and initiating DNA repair. Ataxia telangiectasia and Rad3-related (ATR) protein is a key kinase at the heart of the DDR, responsible for sensing replication stress (RS) and signalling it to S and G2/M checkpoints to facilitate repair. In cancer, loss of G1 checkpoint control and activation of oncogenes that drive replication, result in cancer cells more likely ...
Source: Pharmacology and Therapeutics - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Adeno-associated viral vector-mediated immune responses: Understanding barriers to gene delivery
Publication date: Available online 11 December 2019Source: Pharmacology & TherapeuticsAuthor(s): Natalie F. Nidetz, Michael C. McGee, Longping V. Tse, Chengwen Li, Le Cong, Yunxing Li, Weishan HuangAbstractAdeno-associated viral (AAV) vectors have emerged as the leading gene delivery platform for gene therapy and vaccination. Three AAV-based gene therapy drugs, Glybera, LUXTURNA, and ZOLGENSMA were approved between 2012 and 2019 by the European Medicines Agency and the United States Food and Drug Administration as treatments for genetic diseases hereditary lipoprotein lipase deficiency (LPLD), inherited retinal disease...
Source: Pharmacology and Therapeutics - December 12, 2019 Category: Drugs & Pharmacology Source Type: research

Delving into PARP inhibition from bench to bedside and back
Publication date: Available online 19 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Giovanni Grignani, Alessandra Merlini, Dario Sangiolo, Lorenzo D'Ambrosio, Ymera PignochinoAbstractWith the ever-expanding therapeutic indications and ongoing clinical trials with Poly(adenosine diphosphate-ribose) Polymerase (PARP) inhibitors, it is of outmost importance to stop and rethink what we know and still do not know concerning one of the major revolutions in target therapies in the last decades. Indeed, many PARP inhibitors (PARPi) are able to bind multiple targets, with a plethora of potential interactions with c...
Source: Pharmacology and Therapeutics - December 10, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: December 2019Source: Pharmacology & Therapeutics, Volume 204Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - November 24, 2019 Category: Drugs & Pharmacology Source Type: research

5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future
Publication date: Available online 19 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Sona Vodenkova, Tomas Buchler, Klara Cervena, Veronika Veskrnova, Pavel Vodicka, Veronika VymetalkovaAbstract5-Fluorouracil (5-FU) is an essential component of systemic chemotherapy for colorectal cancer (CRC) in the palliative and adjuvant settings. Over the past four decades, several modulation strategies including the implementation of 5-FU-based combination regimens and 5-FU pro-drugs have been developed and tested to increase the anti-tumor activity of 5-FU and to overcome the clinical resistance.Despite the encouragin...
Source: Pharmacology and Therapeutics - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

Look before you leap: Looking into PARP inhibition from bench to bedside and back
Publication date: Available online 19 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Giovanni Grignani, Alessandra Merlini, Dario Sangiolo, Lorenzo D'Ambrosio, Ymera PignochinoAbstractWith the ever-expanding therapeutic indications and ongoing clinical trials with Poly(adenosine diphosphate-ribose) Polymerase (PARP) inhibitors, it is of outmost importance to stop and rethink what we know and still do not know concerning one of the major revolutions in target therapies in the last decades. Indeed, many PARP inhibitors (PARPi) are able to bind multiple targets, with a plethora of potential interactions with c...
Source: Pharmacology and Therapeutics - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

Targeting miRNAs by histone deacetylase inhibitors (HDACi): Rationalizing epigenetics-based therapies for breast cancer
Publication date: Available online 9 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Meran Keshawa Ediriweera, Somi Kim ChoAbstractMicroRNAs (miRNAs) belong to a group of short RNA molecules of ~22 nucleotides that play a significant role in the regulation of gene expression through post-transcriptional regulatory mechanisms. They can directly interact with their target mRNA molecules and induce target gene silencing. Many investigations over the past decade have revealed the involvement of different miRNAs in essential biological events. The expression of a considerable number of miRNAs is tightly regulated...
Source: Pharmacology and Therapeutics - November 10, 2019 Category: Drugs & Pharmacology Source Type: research

Therapeutic strategy for atherosclerosis based on bone-vascular axis hypothesis
Publication date: Available online 9 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Jeong-Min Kim, Wang-Soo Lee, Jaetaek KimAbstractAs the world's older population grows, the disease burden of atherosclerosis is rapidly increasing, causing significant morbidity and mortality worldwide. Despite recent improvements in the control of vascular risk factors, a significant number of patients still suffer from vascular events and the progression of atherosclerosis. Aging also results in decreased bone mineral density. Since bones are a home for hematopoietic stem cells as well as reservoirs of the minerals require...
Source: Pharmacology and Therapeutics - November 10, 2019 Category: Drugs & Pharmacology Source Type: research

Drug resistance to targeted therapeutic strategies in non-small cell lung cancer
Publication date: Available online 9 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Wen-juan Liu, Yue Du, Ru Wen, Ming Yang, Jian XuAbstractRapidly developing molecular biology techniques have been employed to identify cancer driver genes in specimens from patients with non-small cell lung cancer (NSCLC). Inhibitors and antibodies that specifically target driver gene-mediated signaling pathways to suppress tumor growth and progression are expected to extend the survival time and further improve the quality of life of patients. However, the health of patients with advanced and metastatic NSCLC presents signi...
Source: Pharmacology and Therapeutics - November 10, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: November 2019Source: Pharmacology & Therapeutics, Volume 203Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - November 8, 2019 Category: Drugs & Pharmacology Source Type: research

Pub Note
Publication date: November 2019Source: Pharmacology & Therapeutics, Volume 203Author(s): (Source: Pharmacology and Therapeutics)
Source: Pharmacology and Therapeutics - November 8, 2019 Category: Drugs & Pharmacology Source Type: research

Adolescent Neurodevelopment and Substance Use: Receptor Expression and Behavioral Consequences
Publication date: Available online 7 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Hayley H.A. Thorpe, Shahnaza Hamidullah, Bryan W. Jenkins, Jibran Y. KhokharAbstractAdolescence is the transitional period between childhood and adulthood, during which extensive brain development occurs. Since this period also overlaps with the initiation of drug use, it is important to consider how substance use during this time might produce long-term neurobiological alterations, especially against the backdrop of developmental changes in neurotransmission. Alcohol, cannabis, nicotine, and opioids all produce marked chang...
Source: Pharmacology and Therapeutics - November 8, 2019 Category: Drugs & Pharmacology Source Type: research

Intravital multiphoton microscopy as a novel tool in the field of immunopharmacology
Publication date: Available online 2 November 2019Source: Pharmacology & TherapeuticsAuthor(s): Akito Morimoto, Junichi Kikuta, Masaru IshiiAbstractIntravital microscopy with multiphoton excitation is a recently developed optical imaging technique for deep tissue imaging without fixation or sectioning, which permits examination of fundamental concepts regarding the dynamic nature of cells under physiological and pathological conditions in living animals. This novel technique also offers exciting opportunities for pharmacological research by providing new platforms for the study of cellular dynamics in response to drugs...
Source: Pharmacology and Therapeutics - November 4, 2019 Category: Drugs & Pharmacology Source Type: research

Research and development of κ opioid receptor agonists and δ opioid receptor agonists
Publication date: Available online 22 October 2019Source: Pharmacology & TherapeuticsAuthor(s): Hiroshi Nagase, Akiyoshi SaitohAbstractDelta opioid delta receptor (DOP) agonists were expected to be analgesics and many researchers tried to develop the SNC80 derivatives. However, the derivatives were dropped at the stage of early clinical trials because of undesirable side effects and weak analgesia. On the other hand, DOP agonists have been proposed as attractive candidates for the novel psychotropic drugs. We recently succeeded in synthesizing a novel selective DOP agonist KNT-127. KNT-127 produced neither catalepsy no...
Source: Pharmacology and Therapeutics - October 24, 2019 Category: Drugs & Pharmacology Source Type: research

Autophagy as a novel therapeutic target in vascular calcification
Publication date: Available online 21 October 2019Source: Pharmacology & TherapeuticsAuthor(s): Kanchan Phadwal, Du Feng, Dongxing Zhu, Vicky E MacRaeAbstractThe autophagy pathway is a key regulator of cellular metabolism and homeostasis, and plays a critical role in maintaining normal vascular cell function. It is well recognized that autophagy can regulate endothelial cell homeostasis, vascular smooth muscle cell (VSMC) phenotype transition, and calcium (Ca2+) homeostasis in VSMCs. Emerging evidence has demonstrated that autophagy directly protects against vascular calcification (VC). Crosstalk between endosomes, dys...
Source: Pharmacology and Therapeutics - October 23, 2019 Category: Drugs & Pharmacology Source Type: research