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Current Opinion in Pharmacology

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https://www.readbyqxmd.com/read/28623714/can-the-co-dependence-of-the-immune-system-and-angiogenesis-facilitate-pharmacological-targeting-of-tumours
#1
REVIEW
Lorenzo Mortara, Andrew V Benest, David O Bates, Douglas M Noonan
Tumours elicit a number of mechanisms to induce a reprogramming of innate and adaptive immune cells to their advantage, inducing a pro-angiogenic phenotype. Investigation of these events is now leading to the identification of specific myeloid and lymphoid cell-targeted therapies, as well as of unexplored off-target activities of clinically relevant chemotherapeutic and metabolic drugs. It is also leading to an enhanced understanding of the interplay between angiogenesis and the immune system, and the value of novel co-targeting approaches using both immunotherapy and anti-angiogenic therapy...
June 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28618326/inflammation-as-target-in-cancer-therapy
#2
REVIEW
Giulia Marelli, Antonio Sica, Luca Vannucci, Paola Allavena
Cells of the innate immunity infiltrating tumour tissues promote, rather than halt, cancer cell proliferation and distant spreading. Tumour-Associated Macrophages (TAMs) are abundantly present in the tumour milieu and here trigger and perpetrate a state of chronic inflammation which ultimately supports disease development and contributes to an immune-suppressive environment. Therapeutic strategies to limit inflammatory cells and their products have been successful in pre-clinical tumour models. Early clinical trials with specific cytokine and chemokine inhibitors, or with strategies designed to target TAMs, are on their way in different solid malignancies...
June 12, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28609681/epigenetic-modulation-in-cancer-immunotherapy
#3
REVIEW
Stuart J Gallagher, Elena Shklovskaya, Peter Hersey
The success of immune checkpoint inhibitors in cancer immunotherapy has been widely heralded. However many cancer patients do not respond to immune checkpoint therapy and some relapse due to acquired tumor resistance. Epigenetic targeting may be beneficial in cancer immunotherapy by reversing immune avoidance and escape mechanisms employed by cancer cells, as well as by modulating immune cell differentiation and function. In this manuscript we review recent findings suggesting how epigenetics may be used to improve cancer immunotherapy...
June 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28605657/muscle-as-a-paracrine-and-endocrine-organ
#4
REVIEW
Jimena Giudice, Joan M Taylor
Skeletal muscle cells are highly abundant and metabolically active and are known to 'communicate' their energy demands to other organs through active secretion. Muscle-derived secretory proteins include a variety of cytokines and peptides collectively referred to as 'myokines' that exert autocrine, paracrine or endocrine effects. Analyses of the skeletal muscle secretome revealed that numerous myokines are secreted in response to contraction or strength training, and that these factors not only regulate energy demand but also contribute to the broad beneficial effects of exercise on cardiovascular, metabolic, and mental health...
June 9, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28587973/role-of-centrally-active-cardiovascular-agents-in-cognitive-disorders
#5
REVIEW
Robert J Theobald
Cardiovascular drugs are used to treat patients with cardiac function and hemodynamic problems. Because of the relationship between the cardiovascular (CVS), and central nervous (CNS) systems, alteration of CVS activity can potentially alter CNS function. Of particular concern is regulation of lipids, because of the link between neural functionality, lipids, and cognitive disorders, and perfusion, because of the link between hypo-perfusion and vascular dementia. Positive and negative evidence of the effect of CVS drugs in cognitive disorders is available...
June 3, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28577499/leukocyte-trafficking-in-tumor-microenvironment
#6
REVIEW
Annalisa Del Prete, Tiziana Schioppa, Laura Tiberio, Helena Stabile, Silvano Sozzani
The tumor microenvironment consists of both malignant and non-malignant cells and a plethora of soluble mediators. Different types of tumors have specific tumor microenvironments characterized by distinct chemokines and chemotactic factors that influence leukocyte recruitment. The immune cell infiltrate continuously interacts with stroma cells and influence tumor growth. Emerging evidence suggests that the regulation of the composition and the metabolic state of tumor-associated leukocytes may represent a new promising intervention strategy...
May 31, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28554057/the-immune-regulation-in-cancer-by-the-amino-acid-metabolizing-enzymes-arg-and-ido
#7
REVIEW
Giada Mondanelli, Stefano Ugel, Ursula Grohmann, Vincenzo Bronte
Some enzymes degrading amino acids have evolved in mammals to dampen immune responses and maintain peripheral tolerance. The enzymes metabolizing l-arginine and l-tryptophan are particularly powerful, contributing to restrain immunity towards fetal tissues and establish neonatal tolerance. Solid tumors can hijack these formidable pathways to construct a microenvironment highly unfavorable to anti-tumor T lymphocytes able to recognize them, one of mechanisms for their immune evasion. In this review, we analyze emerging concepts in the cross-talk between cells expressing these enzymes, their immune regulatory functions and pharmacological approaches that can target them to enhance cancer immunotherapy...
May 26, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28551408/epigenetic-mechanisms-of-myeloid-differentiation-in-the-tumor-microenvironment
#8
REVIEW
Javier Rodríguez-Ubreva, Antonio Garcia-Gomez, Esteban Ballestar
Myeloid cells are extremely plastic as they respond and terminally differentiate into a plethora of functional types, in the blood or tissues, in response to a variety of growth factors, cytokines and pathogenic molecules. This plasticity is also manifested by the subversion of normal differentiation into the aberrant generation of a variety of tolerogenic myeloid cells in the tumoral microenvironment, where a variety of factors are released. Epigenetic mechanisms are in great part responsible for the plasticity of myeloid cells both under physiological and tumoral conditions...
May 25, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28551360/immunotherapeutic-properties-of-chemotherapy
#9
REVIEW
Carole Fournier, Thaiz Rivera Vargas, Tiffany Martin, Andréa Melis, Lionel Apetoh
Impressive remissions driven by immunological checkpoint blockade in cancer patients have prompted the scientific community to investigate afresh the crosstalk between cancer cells and the patient's immune system. Preclinical and clinical studies have highlighted that the anticancer efficacy of some conventional chemotherapeutics is based on their ability to restore anticancer immune responses. The current challenge is to understand and circumvent immune resistance mechanisms to chemo- and immunotherapies to design relevant immunotherapy and chemotherapy combinations...
May 24, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28538141/cancer-cell-and-macrophage-cross-talk-in-the-tumor-microenvironment
#10
REVIEW
Nathalie Dehne, Javier Mora, Dmitry Namgaladze, Andreas Weigert, Bernhard Brüne
Tumors are composed of tumor cells, nonmalignant cells, and the vascular system. Among them is intense communication via cell-cell contact-dependent mechanisms and/or soluble messengers. In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming...
May 21, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28528298/emerging-role-of-monoamine-oxidase-as-a-therapeutic-target-for-cardiovascular-disease
#11
REVIEW
Soni Deshwal, Moises Di Sante, Fabio Di Lisa, Nina Kaludercic
In the past decade, accumulating evidence highlighted the role of monoamine oxidases (MAOs) in cardiovascular disease (CVD). MAOs are flavoenzymes located in the outer mitochondrial membrane, responsible for the degradation of neurotransmitters and biogenic amines. During this process they generate hydrogen peroxide, aldehydes and ammonia, species that can target mitochondria and induce mitochondrial dysfunction and cardiomyocyte death. Indeed, MAO inhibition affords cardioprotection in several models of CVD, such as ischemia/reperfusion, heart failure and diabetes...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28528297/biogenic-aldehydes-as-therapeutic-targets-for-cardiovascular-disease
#12
REVIEW
Margaret-Ann M Nelson, Shahid P Baba, Ethan J Andersonc
Aldehydes are continuously formed in biological systems through enzyme-dependent and spontaneous oxidation of lipids, glucose, and primary amines. These highly reactive, biogenic electrophiles can become toxic via covalent modification of proteins, lipids and DNA. Thus, agents that scavenge aldehydes through conjugation have therapeutic value for a number of major cardiovascular diseases. Several commonly-prescribed drugs (e.g., hydralazine) have been shown to have potent aldehyde-conjugating properties which may contribute to their beneficial effects...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28527911/cancer-stem-cells-at-the-forefront-of-personalized-medicine-and-immunotherapy
#13
REVIEW
Micol E Fiori, Lidia Villanova, Ruggero De Maria
Cancer stem cells (CSCs) represent the main target of the current efforts to eradicate cancer, because of their ability to promote metastatic dissemination and survive cytotoxic therapies. Here, we highlight the potential of patient-derived CSCs as an in vitro and in vivo pre-clinical model and of liquid biopsy as a diagnostic, prognostic and predictive tool. We discuss recently developed therapeutic strategies aiming at specifically targeting the cancer stem cell population, particularly focusing on the latest advances in cancer immunotherapy...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28486179/pharmacological-advances-for-treatment-in-duchenne-muscular-dystrophy
#14
REVIEW
Simon Guiraud, Kay E Davies
Duchenne muscular dystrophy (DMD) is a lethal, X-linked muscle-wasting disease caused by lack of dystrophin, essential for muscle fibre integrity. Despite extensive pre-clinical studies, development of an effective treatment has proved challenging. More recently, significant progress has been made with the first drug approval using a genetic approach and the application of pharmacological agents which slow the progression of the disease. Drug development for DMD has mainly used two strategies: (1) the restoration of dystrophin expression or the expression of the compensatory utrophin protein as an efficient surrogate, and (2) the mitigation of secondary downstream pathological mechanisms...
May 6, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28482281/ace-and-sglt2-inhibitors-the-future-for-non-diabetic-and-diabetic-proteinuric-renal-disease
#15
REVIEW
Norberto Perico, Piero Ruggenenti, Giuseppe Remuzzi
Most chronic nephropathies progress relentlessly to end-stage kidney disease. Research in animals and humans has helped our understanding of the mechanisms of chronic kidney disease progression. Current therapeutic strategies to prevent or revert renal disease progression focus on reduction of urinary protein excretion and blood pressure control. Blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors and/or angiotensin II type 1 receptor blockers is the most effective treatment to achieve these purposes in non-diabetic and diabetic proteinuric renal diseases...
May 5, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28472742/cell-cell-communication-in-bone-development-and-whole-body-homeostasis-and-pharmacological-avenues-for-bone-disorders
#16
REVIEW
Young-Eun Park, David S Musson, Dorit Naot, Jillian Cornish
Cell-cell communication plays a crucial role in bone development and maintenance, in health and disease. Our knowledge of the signalling pathways that regulate the communication of osteoblasts, osteoclasts and osteocytes is improving with time, giving us a better understanding of the regulation of the bone remodelling process. Bone cell communication has wider significance than the local tissue environment, however, with bone derived factors playing a role in whole-body homeostasis, including energy metabolism and kidney function...
May 1, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28456094/new-biologics-in-the-treatment-of-rare-glomerular-diseases-of-childhood
#17
REVIEW
Paolo Cravedi, Andrea Angeletti, Giuseppe Remuzzi
Minimal change disease and focal segmental glomerulosclerosis are rare but important causes of end-stage kidney disease in children. Though their pathogenesis is still unclear, evidence of immune abnormalities provided the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant portion of patients and are burdened by significant toxicities...
April 26, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28441626/myobolites-muscle-derived-metabolites-with-paracrine-and-systemic-effects
#18
REVIEW
Ayon Ibrahim, Michael Neinast, Zoltan P Arany
Intracellular metabolism in skeletal muscle has been studied for more than a century and is the stuff of textbooks. In contrast, the extracellular secretion of metabolites by muscle cells, and their effects on non-muscle cells near or far, has been investigated much less extensively. Here, we describe a number of cases in which striated muscle secretes a metabolite that elicits complex responses in other cells or tissues, with involvements in normal physiology as well as obesity, type II diabetes, and cardiac remodeling...
April 22, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28437711/cardiomyocyte-ca-2-homeostasis-as-a-therapeutic-target-in-heart-failure-with-reduced-and-preserved-ejection-fraction
#19
REVIEW
Deborah Peana, Timothy L Domeier
Heart failure is a highly prevalent syndrome of multiple etiologies and associated comorbidities, and aberrant intracellular Ca(2+) homeostasis is a hallmark finding in heart failure patients. The cyclical changes in Ca(2+) concentration within cardiomyocytes control cycles of cardiac contraction and relaxation, and dysregulation of Ca(2+) handling processes leads to systolic dysfunction, diastolic dysfunction, and adverse remodeling. For this reason, greater understanding of Ca(2+) handling mechanisms in heart failure is critical for selection of appropriate treatment strategies...
April 22, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28419894/muscle-cell-communication-in-development-and-repair
#20
REVIEW
Alexis R Demonbreun, Elizabeth M McNally
Under basal conditions, postnatal skeletal muscle displays little cell turnover. With injury, muscle initiates a rapid repair response to reseal damaged membrane, reactivating many developmental pathways to facilitate muscle regeneration and prevent tissue loss. Muscle precursor cells become activated accompanied by differentiation and fusion during both muscle growth and regeneration; inter-cellular communication is required for successful completion of these processes. Cellular communication is mediated by lipids, fusogenic membrane proteins, and exosomes...
April 15, 2017: Current Opinion in Pharmacology
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