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Mas-related G protein-coupled receptors X (MRGPRX): Orphan GPCRs with potential as targets for future drugs Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-08-05 Ghazl Al Hamwi, Yvonne K. Riedel, Sophie Clemens, Vigneshwaran Namasivayam, Dominik T. Thimm, Christa E. Müller
Mas-related G protein-coupled receptors (GPCRs) of subfamily X, designated MRGPRX, are primate-specific orphan receptors that belong to the δ-branch of rhodopsin-like, class A GPCRs. Four distinct subtypes exist, MRGPRX1, -2, -3, and -4, MRGPRX2 having the lowest degree of similarity with the others. Due to their expression on sensory neurons and immune cells, and their roles in pain perception and
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Vitamin D as a chemopreventive agent in colorectal neoplasms. A systematic review and meta-analysis of randomized controlled trials Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-08-01 Georgia Emmanouilidou, Georgios Kalopitas, Dimitra Rafailia Bakaloudi, Evangelia Karanika, Eleni Theocharidou, Georgios Germanidis, Michail Chourdakis
Colorectal cancer (CRC) is the third most common cancer in both sexes and the second in terms of mortality. Apart from genetic predisposition, dietary and lifestyle factors have been implicated in the development of CRC. Several studies suggested that vitamin D (VitD) might be a promising strategy in CRC prevention, while other studies did not confirm this finding. The aim of our study was to examine
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Platelet lipid metabolism in vascular thrombo-inflammation Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-29 Mailin-Christin Manke, Robert Ahrends, Oliver Borst
The function of platelets – and thereby the balance between thrombosis and hemostasis – critically depends on their lipid composition. At the same time, platelets are capable of interacting with inflammatory cells by releasing lipids in a paracrine manner. Over the years, many studies have emphasized the importance of both, membrane and signaling lipids, in the signaling pathways underlying arterial
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Targeting CXCR1 and CXCR2 receptors in cardiovascular diseases Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-28 Kawthar Dhayni, Kazem Zibara, Hawra Issa, Saïd Kamel, Youssef Bennis
CXCR1 and CXCR2 chemokine receptors, mainly activated by interleukin 8 (IL-8 or CXCL8), are expressed in a variety of cells including, leukocytes, fibroblasts, endothelial cells, and smooth muscle cells. Numerous intracellular mediators are activated by these G protein-coupled receptors based on several factors, including the nature of the ligand, its concentration, and the binding sites with the receptor
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Current and emerging therapies for neuroendocrine prostate cancer Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-26 Busola Ruth Alabi, Shiqin Liu, Tanya Stoyanova
Neuroendocrine prostate cancer is a histological variant of prostate cancer that is characterized by aggressiveness, poor clinical outcomes, and expression of neuroendocrine markers. Neuroendocrine prostate cancer usually manifests in late-stage prostate cancer patients who have undergone multiple rounds of anti-androgen therapies but can, although rarely, occur in treatment naïve patients de novo
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Recent advances in metabolism and toxicity of tyrosine kinase inhibitors Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-25 Qi Zhao, Zhanxuan E. Wu, Bin Li, Fei Li
Small molecule tyrosine kinase inhibitors (TKIs) are widely used as anticancer drugs approved by U.S. FDA. However, the toxicities of TKIs to multiple organs have greatly limited their clinical applications. The metabolism of TKIs generates several potentially toxic metabolites in vivo, that can disturb the endogenous metabolism as well as cellular function, leading to organ damage. Therefore, it is
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Chloride channels in the lung: Challenges and perspectives for viral infections, pulmonary arterial hypertension, and chystic fibrosis Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-22 Madhushri Sinha, Diana Zabini, Divya Guntur, Chandran Nagaraj, Peter Enyedi, Horst Olschewski, Wolfgang M. Kuebler, Andrea Olschewski
Fine control over chloride homeostasis in the lung is required to maintain membrane excitability, transepithelial transport as well as intra- and extracellular ion and water homeostasis. Over the last decades, a growing number of chloride channels and transporters have been identified in the cells of the pulmonary vasculature and the respiratory tract. The importance of these proteins is underpinned
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Triple negative breast cancer (TNBC): Non-genetic tumor heterogeneity and immune microenvironment: Emerging treatment options Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-21 Jae Young So, Joyce Ohm, Stan Lipkowitz, Li Yang
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intra-tumoral heterogeneity, and frequently develops resistance to therapies. Tumor heterogeneity and lack of biomarkers are thought to be some of the most difficult challenges driving therapeutic resistance and relapse. This review will summarize current therapy for TNBC, studies in treatment resistance and relapse
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Mutual regulation of noncoding RNAs and RNA modifications in psychopathology: Potential therapeutic targets for psychiatric disorders? Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-21 Bing Han, Wen Xi, Yiting Hong, Liyuan Gu, Yue Chao, Lu Li, ChenChen Liu, Li Yang, Jie Chao, Honghong Yao
The human brain is specifically enriched for multiple classes of noncoding RNAs (ncRNAs) and for particular RNA modifications, both of which are increasingly recognized to contribute to the etiology and pathophysiology of psychiatric disorders. Here, we summarize the rapidly developing areas of basic research in brain-specific ncRNA biology and the functional and pathological consequences of different
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Allosteric modulation of GPCRs: From structural insights to in silico drug discovery Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-18 Margherita Persechino, Janik Björn Hedderich, Peter Kolb, Daniel Hilger
G protein-coupled receptors (GPCRs) play critical roles in human physiology and are one of the prime targets for marketed drugs. While traditional drug discovery programs have focused on the development of ligands targeting the binding site of endogenous ligands (orthosteric site), allosteric modulators offer new avenues for the regulation of GPCR function with potential therapeutic benefits. Recent
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Game of clones: Battles in the field of carcinogenesis Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-15 Zahraa Rahal, Ansam Sinjab, Ignacio I. Wistuba, Humam Kadara
Recent advances in bulk sequencing approaches as well as genomic decoding at the single-cell level have revealed surprisingly high somatic mutational burdens in normal tissues, as well as increased our understanding of the landscape of “field cancerization”, that is, molecular and immune alterations in mutagen-exposed normal-appearing tissues that recapitulated those present in tumors. Charting the
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Immune-related adverse events of cancer immunotherapies targeting kinases Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-14 Manuel Ramos-Casals, Alejandra Flores-Chávez, Pilar Brito-Zerón, Olivier Lambotte, Xavier Mariette
Immunotherapies are designed to target a specific molecule of the immune system and emerged at the end of the last century as effective therapies the treatment of a widening spectrum of inflammatory diseases. Paradoxically, their use was quickly linked to the development of autoimmune disorders, whose treatment indications often include the very biological agent producing the adverse event. The scenario
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Bispecific antibodies for the treatment of neuroblastoma Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-10 Madelyn Espinosa-Cotton, Nai-Kong V. Cheung
Bispecific antibodies (BsAb) are a new generation of antibody-based therapy, conveying artificial specificity to polyclonal T cells or radiohaptens. These drugs have been successfully implemented to cure hematologic malignancies and are under clinical investigation for solid tumors including HRNB. BsAbs designed to engage T cells or increase the therapeutic index of radiotherapy hold the potential
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Inflammation in kidney repair: Mechanism and therapeutic potential Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-05 Ying Fu, Yu Xiang, Honglin Li, Anqun Chen, Zheng Dong
The kidney has a remarkable ability of repair after acute kidney injury (AKI). However, when injury is severe or persistent, the repair is incomplete or maladaptive and may lead to chronic kidney disease (CKD). Maladaptive kidney repair involves multiple cell types and multifactorial processes, of which inflammation is a key component. In the process of inflammation, there is a bidirectional interplay
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Bile acid metabolism and signaling, the microbiota, and metabolic disease Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-07-02 Jingwei Cai, Bipin Rimal, Changtao Jiang, John Y.L. Chiang, Andrew D. Patterson
The diversity, composition, and function of the microbial community inhabiting the human gastrointestinal tract contributes to host health through its role in producing energy or signaling molecules that regulate metabolic and immunologic functions. Bile acids are potent metabolic and immune signaling molecules synthesized from cholesterol in the liver and then transported to the intestine where they
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Prognostic and predictive molecular biomarkers in advanced colorectal cancer Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-30 Valentino Martelli, Alessandro Pastorino, Alberto F. Sobrero
The revolution of precision medicine has produced unprecedented seismic shifts in the treatment paradigm of advanced cancers. Among the major killers, colorectal cancer (CRC) is far behind the others. In fact, the great successes obtained in breast, NSCLC, melanoma, and genitourinary tract tumors have been observed only in fewer than 5 % metastatic colorectal cancer (mCRC): those with the mismatch
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Clozapine’s multiple cellular mechanisms: What do we know after more than fifty years? A systematic review and critical assessment of translational mechanisms relevant for innovative strategies in treatment-resistant schizophrenia Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-25 Andrea de Bartolomeis, Licia Vellucci, Annarita Barone, Mirko Manchia, Vincenzo De Luca, Felice Iasevoli, Christoph U. Correll
Almost fifty years after its first introduction into clinical care, clozapine remains the only evidence-based pharmacological option for treatment-resistant schizophrenia (TRS), which affects approximately 30% of patients with schizophrenia. Despite the long-time experience with clozapine, the specific mechanism of action (MOA) responsible for its superior efficacy among antipsychotics is still elusive
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Cholesterol crystals and atherosclerotic plaque instability: Therapeutic potential of Eicosapentaenoic acid Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-27 M. John Chapman, R. Preston Mason
Atherosclerotic plaques associated with acute coronary syndromes (ACS), i.e. culprit lesions, frequently feature a ruptured fibrous cap with thrombotic complications. On imaging, these plaques exhibit a low attenuation, lipid-rich, necrotic core containing cholesterol crystals and are inherently unstable. Indeed, cholesterol crystals are causally associated with plaque vulnerability in vivo; their
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Progressive massive fibrosis: An overview of the recent literature Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-19 David N. Weissman
This review provides an overview of literature addressing progressive massive fibrosis (PMF) from September 2009 to the present. Advances are described in understanding its pathophysiology, epidemiology of the occurrence of PMF and related conditions, the impact of PMF on pulmonary function, advances in imaging of PMF, and factors affecting progression of pneumoconiosis in dust-exposed workers to PMF
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“RB-reactivator screening” as a novel cell-based assay for discoveries of molecular targeting agents including the first-in-class MEK inhibitor trametinib (trade name: Mekinist) Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-19 Toshiyuki Sakai
The retinoblastoma gene (RB) was discovered as the first tumor-suppressor gene. It was subsequently shown to be inactivated in most malignant tumors, particularly at the protein level. Therefore, many activated oncogenes as well as inactivated tumor-suppressor genes inactivate the function of the RB protein. I hypothesized that most of the molecular-targeting agents against activated oncogenes may
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Antibody drug conjugates: The dos and don'ts in clinical development Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-20 Anthony W. Tolcher
Antibody Drug Conjugates (ADCs) entered clinical trials in the mid 1990s to selectively deliver cytotoxic chemotherapy to cancer cells with the goal to increase the antitumor activity and decrease normal tissue toxicity. Over nearly 30 years of development the ADC platform has become established with now 11 approved agents and many more in the pipeline. This review is designed to highlight some of
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Monoclonal antibody therapeutics for infectious diseases: Beyond normal human immunoglobulin Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-20 Ryota Otsubo, Teruhito Yasui
Antibody therapy is effective for treating infectious diseases. Due to the coronavirus disease 2019 (COVID-19) pandemic and the rise of drug-resistant bacteria, rapid development of neutralizing monoclonal antibodies (mAbs) to treat infectious diseases is urgently needed. Using a therapeutic human mAb with the lowest immunogenicity is recommended, because chimera and humanized mAbs are occasionally
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Targeting cancer-associated fibroblasts: Challenges, opportunities and future directions Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-17 Benjamin H. Jenkins, Josephine F. Buckingham, Christopher J. Hanley, Gareth J. Thomas
Cancer-associated fibroblasts (CAFs) are a common cell in the tumour microenvironment with diverse tumour-promoting functions. Their presence in tumours is commonly associated with poor prognosis making them attractive therapeutic targets, particularly in the context of immunotherapy where CAFs have been shown to promote resistance to checkpoint blockade. Previous attempts to inhibit CAFs clinically
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Development and clinical translation of P2X7 receptor antagonists: A potential therapeutic target in coronary artery disease? Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-16 Elijah Genetzakis, Jayson Gilchrist, Michael Kassiou, Gemma A. Figtree
The purinoceptor 7 receptor (P2X7R) plays an important role in promoting inflammation in response to accumulating damage-associated molecular patterns (DAMPs) released from stressed or apoptotic cells and has been connected to various pathological conditions. The initial investment by large pharmaceutical companies such as AstraZeneca and Pfizer led to the development of several classes of P2X7R antagonists
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Targeting CDK7 in oncology: The avenue forward Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-11 Zhi-Mei Li, Guan Liu, Ya Gao, Ming-Gao Zhao
Cyclin-dependent kinase (CDK) 7 is best characterized for the ability to regulate biological processes, including the cell cycle and gene transcription. Abnormal CDK7 activity is observed in various tumours and represents a driving force for tumourigenesis. Therefore, CDK7 may be an appealing target for cancer treatment. Whereas, the enthusiasm for CDK7-targeted therapeutic strategy is mitigated due
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Pharmacological treatment of cardiogenic shock – A state of the art review Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-10 Raphael Romano Bruno, Georg Wolff, Malte Kelm, Christian Jung
Cardiogenic shock is a clinical syndrome of impaired tissue perfusion caused by primary cardiac dysfunction and inadequate cardiac output. It represents one of the most lethal clinical conditions in intensive care medicine with mortality >40%. Management of different clinical presentations of cardiogenic shock includes guidance of cardiac preload, afterload, heart rate and contractility by differential
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CNS border-associated macrophages in the homeostatic and ischaemic brain Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-06-03 Gabriela Gerganova, Alexandra Riddell, Alyson A. Miller
CNS border-associated macrophages (BAMs) are a small population of specialised macrophages localised in the choroid plexus, meningeal and perivascular spaces. Until recently, the function of this elusive cell type was poorly understood and largely overlooked, especially in comparison to microglia, the primary brain resident immune cell. However, the recent single cell immunophenotyping or transcriptomic
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The role of drug-metabolizing enzymes in synthetic lethality of cancer Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-27 Zekun Zeng, Wenfang Zheng, Peng Hou
Drug-metabolizing enzymes (DMEs) have shown increasing importance in anticancer therapy. It is not only due to their effect on activation or deactivation of anticancer drugs, but also because of their extensive connections with pathological and biochemistry changes during tumorigenesis. Meanwhile, it has become more accessible to discovery anticancer drugs that selectively targeted cancer cells with
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Superconserved receptors expressed in the brain: Expression, function, motifs and evolution of an orphan receptor family Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-26 Claudia Stäubert, Monika Wozniak, Nadine Dupuis, Céline Laschet, Thanigaimalai Pillaiyar, Julien Hanson
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MicroRNAs in drug addiction: Current status and future perspectives Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-21 Yue Zhao, Feng Qin, Shuang Han, Shu Li, Ying Zhao, Hongbo Wang, Jingwei Tian, Xiaobo Cen
Drug addiction is a chronic and relapsing brain disorder characterized by compulsive drug seeking and continued drug use despite adverse consequences. The high prevalence and social burden of addiction is indisputable; however, the available intervention is insufficient. Abnormal gene expression is observed in reward-related brain regions in animal models of addiction. The modulation of gene expression
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Cannabinoids and the endocannabinoid system in fibromyalgia: A review of preclinical and clinical research Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-21 Stephanie L. Bourke, Anne Katrin Schlag, Saoirse Elizabeth O'Sullivan, David J. Nutt, David P. Finn
Characterised by chronic widespread musculoskeletal pain, generalised hyperalgesia, and psychological distress, fibromyalgia (FM) is a significant unmet clinical need. The endogenous cannabinoid system plays an important role in modulating both pain and the stress response. Here, we appraise the evidence, from preclinical and clinical studies, for a role of the endocannabinoid system in FM and the
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Crosstalk between adenosine receptors and CYP450-derived oxylipins in the modulation of cardiovascular, including coronary reactive hyperemic response Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-18 Mohammed A. Nayeem, Ahmad Hanif, Werner J. Geldenhuys, Stephanie Agba
Adenosine is a ubiquitous endogenous nucleoside or autacoid that affects the cardiovascular system through the activation of four G-protein coupled receptors: adenosine A1 receptor (A1AR), adenosine A2A receptor (A2AAR), adenosine A2B receptor (A2BAR), and adenosine A3 receptor (A3AR). With the rapid generation of this nucleoside from cellular metabolism and the widespread distribution of its four
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Stress- and drug-induced neuroimmune signaling as a therapeutic target for comorbid anxiety and substance use disorders Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-14 Cora E. Smiley, Susan K. Wood
Stress and substance use disorders remain two of the most highly prevalent psychiatric conditions and are often comorbid. While individually these conditions have a debilitating impact on the patient and a high cost to society, the symptomology and treatment outcomes are further exacerbated when they occur together. As such, there are few effective treatment options for these patients, and recent investigation
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The roles of TGF-β and VEGF pathways in the suppression of antitumor immunity in melanoma and other solid tumors Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-14 Melissa T. Bu, Pallavi Chandrasekhar, Lizhong Ding, Willy Hugo
Immune checkpoint blockade (ICB) has become well-known in cancer therapy, strengthening the body's antitumor immune response rather than directly targeting cancer cells. Therapies targeting immune inhibitory checkpoints, such as PD-1, PD-L1, and CTLA-4, have resulted in impressive clinical responses across different types of solid tumors. However, as with other types of cancer treatments, ICB-based
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Mitochondrial metabolism mediated macrophage polarization in chronic lung diseases Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-13 Ting Dong, Xinyi Chen, Haochuan Xu, Yaxin Song, Huirui Wang, Yinghui Gao, Jingcheng Wang, Ruiqing Du, Hongxiang Lou, Ting Dong
As the first line of defence in the lung, alveolar macrophage contributes to maintaining lung immune homoeostasis. Characterized by the heterogeneity and plasticity, macrophages polarize into two pro-inflammatory and anti-inflammatory phenotypes regarding the biological and pathological environment. In the past decade, numerous studies have revolutionized the relationship between cellular metabolism
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Clinical implications of tristetraprolin (TTP) modulation in the treatment of inflammatory diseases Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-05 Brittany L. Snyder, Perry J. Blackshear
Abnormal regulation of pro-inflammatory cytokine and chemokine mediators can contribute to the excess inflammation characteristic of many autoimmune diseases, such as rheumatoid arthritis, psoriasis, Crohn's disease, type 1 diabetes, and many others. The tristetraprolin (TTP) family consists of a small group of related RNA-binding proteins that bind to preferred AU-rich binding sites within the 3′-untranslated
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The future of targeted kinase inhibitors in melanoma Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-05-02 Signe Caksa, Usman Baqai, Andrew E. Aplin
Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mutant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes
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Advances in understanding cancer-associated neurogenesis and its implications on the neuroimmune axis in cancer Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-29 Ismail Yaman, Didem Ağaç Çobanoğlu, Tongxin Xie, Yi Ye, Moran Amit
Nerves and immunologic mediators play pivotal roles in body homeostasis by interacting with each other through diverse mechanisms. The spread of nerves in the tumor microenvironment increases tumor cell proliferation and disease progression, and this correlates with poor patient outcomes. The effects of sympathetic and parasympathetic nerves on cancer regulation are being investigated. Recent findings
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Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-27 Sanket B. Raut, Padmaja A. Marathe, Liza van Eijk, Rajaraman Eri, Manoj Ravindran, David M. Benedek, Robert J. Ursano, Juan J. Canales, Luke R. Johnson
Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy
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Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-27 Jian Yang, John E. Hall, Pedro A. Jose, Ken Chen, Chunyu Zeng
G protein-coupled receptors (GPCRs) mediate cellular responses to diverse extracellular stimuli that play vital roles in the regulation of biology, including behavior. Abnormal G protein-coupled receptor kinase (GRK)-mediated regulation of GPCR function is involved in the pathogenesis of hypertension. Among the seven GRK subtypes, GRK4 has attracted attention because of its constitutive activity and
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Clinical advances in oncolytic virotherapy for pediatric brain tumors Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-26 Gelare Ghajar-Rahimi, Kyung-Don Kang, Stacie K. Totsch, Sam Gary, Abbey Rocco, Sarah Blitz, Kara Kachurak, M.R. Chambers, Rong Li, Elizabeth A. Beierle, Asim Bag, James M. Johnston, James M. Markert, Joshua D. Bernstock, Gregory K. Friedman
Malignant brain tumors constitute nearly one-third of cancer diagnoses in children and have recently surpassed hematologic malignancies as the most lethal neoplasm in the pediatric population. Outcomes for children with brain tumors are unacceptably poor and current standards of care—surgical resection, chemotherapy, and radiation—are associated with significant long-term morbidity. Oncolytic virotherapy
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The IL-18/IL-18R1 signalling axis: Diagnostic and therapeutic potential in hypertension and chronic kidney disease Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-21 Jordyn M. Thomas, Brooke M. Huuskes, Christopher G. Sobey, Grant R. Drummond, Antony Vinh
Chronic kidney disease (CKD) is inherently an inflammatory condition, which ultimately results in the development of end stage renal disease or cardiovascular events. Low-grade inflammatory diseases such as hypertension and diabetes are leading causes of CKD. Declines in renal function correlate with elevated circulating pro-inflammatory cytokines in patients with these conditions. The inflammasome
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The treatment strategy of connective tissue disease associated pulmonary arterial hypertension: Evolving into the future Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-21 Jiuliang Zhao, Qian Wang, Xiaoyue Deng, Junyan Qian, Zhuang Tian, Yongtai Liu, Mengtao Li, Xiaofeng Zeng
Pulmonary arterial hypertension (PAH) is a frequent but severe vascular complication of patients with connective tissue diseases (CTDs) and a major cause of significant morbidity and mortality in these patients. Over the past few decades, effective therapies that targeting key signaling pathways involved in PAH have significantly improved patients symptoms and quality of life, and CTD-PAH patients
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Corrigendum to "Apical sodium-dependent bile acid transporter, drug target for bile acid related diseases and delivery target for prodrugs: Current and future challenges" [Pharmacology & Therapeutics 212 (2020) 107539]. Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-15 Ming Li,Qian Wang,Yong Li,Shengtian Cao,Yingjun Zhang,Zhongqing Wang,Guozhu Liu,Jing Li,Baohua Gu
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HDACs and the epigenetic plasticity of cancer cells: Target the complexity Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-14 Claudio Brancolini, Teresa Gagliano, Martina Minisini
Cancer cells must adapt to the hostile conditions of the microenvironment in terms of nutrition, space, and immune system attack. Mutations of DNA are the drivers of the tumorigenic process, but mutations must be able to hijack cellular functions to sustain the spread of mutant genomes. Transcriptional control is a key function in this context and is controlled by the rearrangement of the epigenome
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Regulation of feeding and therapeutic application of bioactive peptides Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-14 Hiroaki Ueno, Weidong Zhang, Masamitsu Nakazato
Obesity and obesity-related diseases, such as diabetes mellitus and dyslipidemia, are worldwide pandemics; therefore, studies have been conducted energetically to elucidate the mechanism of obesity and develop anti-obesity drugs. Robust progress in the peptide chemistry and molecular biology has identified many peptides that regulate appetite and energy metabolism over the past dozen years. Several
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Novel strategies exploiting interleukin-12 in cancer immunotherapy Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-14 Assunta Cirella, Carlos Luri-Rey, Claudia Augusta Di Trani, Alvaro Teijeira, Irene Olivera, Elixabet Bolaños, Eduardo Castañón, Belen Palencia, Davide Brocco, Myriam Fernández-Sendin, Fernando Aranda, Pedro Berraondo, Ignacio Melero
Interleukin-12 is considered a potent agent to enhance antitumor immune responses. It belongs to a family of heterodimeric cytokines with key roles in the up-regulation and down-regulation of cellular immunity. Since its discovery, recombinant IL-12 was found to exert potent antitumor effects in rodent tumor models and was rapidly tested in the clinic with an unfavorable benefit/toxicity profile. Localized
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Unraveling diverse roles of noncoding RNAs in various human papillomavirus negative cancers Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-11 Xin Chen, Yi Liu, Hejing Liu, Zhi-wei Wang, Xueqiong Zhu
Human papillomavirus (HPV)-negative tumors distinguish from cancers associated with HPV infection. Due to its high rate of lymph node metastasis and difficulty in inchoate discover and diagnosis, the treatment efficacy of HPV-negative cancers is unsatisfactory. Epidemiological evidence suggests that HPV-negative tumor patients have a poor prognosis, and the mortality is higher than that of cancer patients
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The role of hypoxia-inducible factors in cardiovascular diseases Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-09 Baoqi Yu, Xia Wang, Yanting Song, Guomin Xie, Shiyu Jiao, Li Shi, Xuejie Cao, Xinyao Han, Aijuan Qu
Cardiovascular diseases are the leading cause of death worldwide. During the development of cardiovascular diseases, hypoxia plays a crucial role. Hypoxia-inducible factors (HIFs) are the key transcription factors for adaptive hypoxic responses, which orchestrate the transcription of numerous genes involved in angiogenesis, erythropoiesis, glycolytic metabolism, inflammation, and so on. Recent studies
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Recent advances in the pharmacological therapy of chronic heart failure: Evidence and guidelines Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-09 Hiroyuki Tsutsui
Heart failure (HF) is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and associated with elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. It is classified according to left ventricular ejection fraction (LVEF): HF with reduced EF (HFrEF) with an LVEF of ≤40%, HF with mildly reduced EF (HFmrEF)
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Triggering receptor expressed on myeloid cells-1 (TREM-1) inhibition in atherosclerosis Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-04 Anastasios Panagopoulos, Saurabhi Samant, Jules Joel Bakhos, Martin Liu, Behram Khan, Janaki Makadia, Fayaz Muhammad, Forrest M. Kievit, Devendra K. Agrawal, Yiannis S. Chatzizisis
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a transmembrane protein expressed on endothelial cells, white blood cells, smooth muscle cells and platelets. TREM-1 plays an important role in innate immunity. TREM-1 activation pathways are implicated both in sepsis and in non-infectious inflammatory conditions, including atherosclerosis. TREM-1 enhances the subendothelial lipid accumulation
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Inflammation and oxidative stress as mediators of the impacts of environmental exposures on human pregnancy: Evidence from oxylipins Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-04-01 Barrett M. Welch, Erin E. McNell, Matthew L. Edin, Kelly K. Ferguson
Inflammation and oxidative stress play major roles in healthy and pathological pregnancy. Environmental exposure to chemical pollutants may adversely affect maternal and fetal health in pregnancy by dysregulating these critical underlying processes of inflammation and oxidative stress. Oxylipins are bioactive lipids that play a major role in regulating inflammation and increasing lines of evidence
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Distinct mechanisms underlying therapeutic potentials of CD20 in neurological and neuromuscular disease Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-31 Tao-Xiang Chen, Yuan-Teng Fan, Bi-Wen Peng
Cluster of differentiation 20 (CD20) is an integral membrane protein expressed mainly on different developmental stages of B lymphocytes and rarely on T lymphocytes, and it functions as a link to B cell antigen receptor (BCR) and immune microenvironment via regulating calcium ion influx, cell cycle progression and interaction between isotypic BCRs and their co-receptors. Diverse therapeutic monoclonal
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Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-28 Dustin J. Flanagan, Simon A. Woodcock, Caroline Phillips, Catherine Eagle, Owen J. Sansom
Gastrointestinal cancers are responsible for more cancer deaths than any other system of the body. This review summarises how Wnt pathway dysregulation contributes to the development of the most common gastrointestinal cancers, with a particular focus on the nature and frequency of upstream pathway aberrations. Tumors with upstream aberrations maintain a dependency on the presence of functional Wnt
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Why medicines work Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-26 David C. Swinney
The interactions of candidate medicines with physiology that have yielded therapeutics are a small subset of the total interactions investigated. To be useful the interactions must initiate molecular actions that fix a disease phenotype. While much is known about the targets for successful interactions and the disease phenotypes, much less is understood of the molecular actions that connect the initial
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The contribution of altered neuronal autophagy to neurodegeneration Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-26 Alessia Filippone, Emanuela Esposito, Deborah Mannino, Nicholas Lyssenko, Domenico Praticò
Defects in cellular functions related to altered protein homeostasis and associated progressive accumulation of pathological intracellular material is a critical process involved in the pathogenesis of many neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Autophagy is an essential mechanism that ensures neuronal health by removing long-lived proteins or defective
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Anti-cancer activity of sustained release capsaicin formulations Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-26 Justin C. Merritt, Stephen D. Richbart, Emily G. Moles, Ashley J. Cox, Kathleen C. Brown, Sarah L. Miles, Paul T. Finch, Joshua A. Hess, Maria T. Tirona, Monica A. Valentovic, Piyali Dasgupta
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Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-26 Xiaohua Pan, Qing Zhu, Li-Long Pan, Jia Sun
Inflammatory bowel disease (IBD), comprised of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory disease of the gastrointestinal tract that closely related to immune dysfunction. Macrophages are the key gatekeeper of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages have been recognized as attractive targets to develop new therapeutic approaches
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The roles of N6-methyladenosine methylation in the regulation of bone development, bone remodeling and osteoporosis Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-25 Yuan Li, Li Meng, Baobing Zhao
N6-methyladenosine (m6A), a novel epitranscriptomic RNA modification, plays crucial roles in a variety of biological processes and diseases. Recently, there are growing evidence supporting that m6A methylation is essential for bone development and homeostasis through the regulation of key genes by regulating RNA stability, localization, turnover and translation efficiency. In this review, we summarized
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The emerging potential of Aptamers as therapeutic agents in infection and inflammation Pharmacol. Therapeut. (IF 13.4) Pub Date : 2022-03-18 Matthew Stephens
Refined from pools of random sequence oligonucleotides, nucleic acid aptamers have been found to bind an almost limitless array of targets, including clinically-relevant proteins. Comparable to their antibody counterparts, aptamers display significant advantages over protein-based therapeutics in part due to their flexibility in chemical modifications, small size, and scalability. Despite the perceived