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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/28342824/development-of-car-t-cells-designed-to-improve-antitumor-efficacy-and-safety
#1
REVIEW
Janneke E Jaspers, Renier J Brentjens
Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models...
March 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28336474/the-evolution-of-heart-failure-with-reduced-ejection-fraction-pharmacotherapy-what-do-we-have-and-where-are-we-going
#2
REVIEW
Ahmed Selim, Ronald Zolty, Yiannis S Chatzizisis
Cardiovascular diseases represent a leading cause of mortality and increased healthcare expenditure worldwide. Heart failure, which simply describes an inability of the heart to meet the body's needs, is the end point for many other cardiovascular conditions. The last three decades have witnessed significant efforts aiming at the discovery of treatments to improve the survival and quality of life of patients with heart failure; many were successful, while others failed. Given that most of the successes in treating heart failure were achieved in patients with reduced left ventricular ejection fraction (HFrEF), we constructed this review to look at the recent evolution of HFrEF pharmacotherapy...
March 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28336473/unravelling-the-complexities-of-vascular-smooth-muscle-ion-channels-fine-tuning-of-activity-by-ancillary-subunits
#3
REVIEW
Thomas A Jepps
Which ion channel is the most important for regulating vascular tone? Which one is responsible for controlling the resting membrane potential or repolarization? Which channels are recruited by different intracellular signalling pathways or change in certain vascular diseases? Many different ion channels have been identified in the vasculature over the years and claimed as future therapeutic targets. Unfortunately, several of these ion channels are not just found in the vasculature, with many of them also found to have prominent functional roles in different organs of the body, which then leads to off-target effects...
March 20, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322974/current-modalities-in-cancer-immunotherapy-immunomodulatory-antibodies-cars-and-vaccines
#4
REVIEW
Jason Lohmueller, Olivera J Finn
Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322973/imidazoline-i2-receptors-an-update
#5
REVIEW
Jun-Xu Li
Since first introduced more than two decades ago, the research in imidazoline I2 receptors has been steadily increasing. This review provides an update on the current status of I2 receptor pharmacology. Imidazoline I2 receptors or I2 binding sites refer to several (at least four) different proteins that bind to [(3)H]-idazoxan and [(3)H]-2-BFI with high affinity. The molecular identities of the proteins remain elusive. One of the proteins (45 kD) seems to be consistent with the identity of brain creatine kinase...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322972/potential-role-of-cyp1b1-in-the-development-and-treatment-of-metabolic-diseases
#6
REVIEW
Fei Li, Weifeng Zhu, Frank J Gonzalez
Cytochrome P450 1B1 (CYP1B1), a member of CYP450s, is expressed in liver and extrahepatic tissues carries out the metabolism of numerous xenobiotics, including the metabolic activation of polycyclic aromatic hydrocarbons. Surprisingly, CYP1B1 was also shown to be important in regulating endogenous metabolic pathways, including the metabolism of steroid hormones, fatty acids, melatonin, and vitamins. CYP1B1 and nuclear receptors including peroxisome proliferator-activated receptors (PPARs), estrogen receptor (ER), and retinoic acid receptors (RAR) contribute to the maintenance of the homeostasis of these endogenous compounds...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322971/effects-and-mechanisms-of-compound-chinese-medicine-and-major-ingredients-on-microcirculatory-dysfunction-and-organ-injury-induced-by-ischemia-reperfusion
#7
REVIEW
Jing-Yan Han, Quan Li, Zhi-Zhong Ma, Jing-Yu Fan
Microcirculation dysfunction and organ injury after ischemia and reperfusion (I/R) result from a complex pathologic process consisting of multiple links, with metabolism impairment in the ischemia phase and oxidative stress in the reperfusion phase as initiators, and any treatment targeting a single link is insufficient to cope with this. Compound Chinese medicine (CCM) has been applied in clinics in China and some Asian nations for more than 2000 years. Studies over the past decades revealed the protective and therapeutic effect of CCMs and major ingredients on I/R-induced microcirculatory dysfunction and tissue injury in the heart, brain, liver, intestine, and so on...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28322970/gold-nanoparticles-radiations-and-the-immune-system-current-insights-into-the-physical-mechanisms-and-the-biological-interactions-of-this-new-alliance-towards-cancer-therapy
#8
REVIEW
Nikolaos M Dimitriou, George Tsekenis, Evangelos C Balanikas, Athanasia Pavlopoulou, Melina Mitsiogianni, Theodora Mantso, George Pashos, Andreas G Boudouvis, Ioannis N Lykakis, Georgios Tsigaridas, Mihalis I Panayiotidis, Vassilios Yannopapas, Alexandros G Georgakilas
Considering both cancer's serious impact on public health and the side effects of cancer treatments, strategies towards targeted cancer therapy have lately gained considerable interest. Employment of gold nanoparticles (GNPs), in combination with ionizing and non-ionizing radiations, has been shown to improve the effect of radiation treatment significantly. GNPs, as high-Z particles, possess the ability to absorb ionizing radiation and enhance the deposited dose within the targeted tumors. Furthermore, they can convert non-ionizing radiation into heat, due to plasmon resonance, leading to hyperthermic damage to cancer cells...
March 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315359/antibodies-and-associates-partners-in-targeted-drug-delivery
#9
REVIEW
Patrick J Kennedy, Carla Oliveira, Pedro L Granja, Bruno Sarmento
Monoclonal antibodies (mAbs) are well established in the clinic due to their specificity and affinity to a diverse array of biochemical targets. More recently, mAbs are being exploited as targeting agents in modern drug delivery systems, aiming to bypass normal host tissue and to accumulate a therapeutic agent to a specific tissue or cell for enhanced pharmacology. At sizes ranging from ~10-100nm, antibody-based bioconjugates have opened up a whole new realm of clinical possibilities with several platforms emerging on the market...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315358/isocitrate-dehydrogenase-idh-inhibition-as-treatment-of-myeloid-malignancies-progress-and-future-directions
#10
REVIEW
Vivek A Upadhyay, Andrew M Brunner, Amir T Fathi
Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme. Over the last two decades, there has been a growing focus on the metabolic derangements that occur with IDH1 and IDH2 mutations. The altered IDH protein leads to accumulation of 2-hydroxyglutarate (2-HG), a metabolite with oncogenic activity via epigenetic mechanisms. The advent of IDH inhibitors has engendered hope in novel and targeted therapies in IDH1/2 mutant myeloid malignancies. We here summarize the basic physiology of IDH, the metabolic and oncogenic consequences of mutant IDH1/2, and the clinical significance of IDH inhibition in hematologic malignancies...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28279785/epigenetic-interventions-for-epileptogenesis-a-new-frontier-for-curing-epilepsy
#11
REVIEW
Iyan Younus, Doodipala Samba Reddy
This article highlights the emerging therapeutic potential of specific epigenetic modulators as promising antiepileptogenic or disease-modifying agents for curing epilepsy. Currently, there is an unmet need for antiepileptogenic agents that truly prevent the development of epilepsy in people at risk. There is strong evidence that epigenetic signaling, which exerts high fidelity regulation of gene expression, plays a crucial role in the pathophysiology of epileptogenesis and chronic epilepsy. These modifications are not hard-wired into the genome and are constantly reprogrammed by environmental influences...
March 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28279784/emerging-role-of-dubs-in-tumor-metastasis-and-apoptosis-therapeutic-implication
#12
REVIEW
Mingjing He, Zhuan Zhou, George Wu, Qianming Chen, Yong Wan
Malfunction of ubiquitin-proteasome system is tightly linked to tumor formation and tumor metastasis. Targeting the ubiquitin-pathway provides a new strategy for anti-cancer therapy. Despite the parts played by ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in governing the multiple steps of the metastatic cascade, including local invasion, dissemination, and eventual colonization of the tumor to distant organs. Both deregulated ubiquitination and deubiquitination could lead to dysregulation of various critical events and pathways such as apoptosis and epithelial-mesenchymal transition (EMT)...
March 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28245991/trem-1-and-its-potential-ligands-in-non-infectious-diseases-from-biology-to-clinical-perspectives
#13
REVIEW
Alessandra Tammaro, Marc Derive, Sebastien Gibot, Jaklien C Leemans, Sandrine Florquin, Mark C Dessing
Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on the majority of innate immune cells and to a lesser extent on parenchymal cells. Upon activation, TREM-1 can directly amplify an inflammatory response. Although it was initially demonstrated that TREM-1 was predominantly associated with infectious diseases, recent evidences shed new light into its role in sterile inflammatory diseases. Indeed, TREM-1 receptor and its signaling pathways contribute to the pathology of several non-infectious acute and chronic inflammatory diseases, including atherosclerosis, ischemia reperfusion-induced tissue injury, colitis, fibrosis and cancer...
February 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28249706/preincubation-dependent-and-long-lasting-inhibition-of-organic-anion-transporting-polypeptide-oatp-and-its-impact-on-drug-drug-interactions
#14
REVIEW
Yoshihisa Shitara, Yuichi Sugiyama
Preincubation with cyclosporin A (CsA), a potent inhibitor of organic anion transporting polypeptide 1B1 (OATP1B1) and OATP1B3, enhanced its inhibitory effects on these transporters in vitro. A similar effect was observed upon preincubation with some other inhibitors. Removing these from the incubation media did not readily reverse the inhibition on OATP1B1 and OATP1B3. This preincubation-dependent long-lasting inhibition appeared to be related to CsA concentration in the cells, in addition to that in the incubation media...
February 26, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28232275/recent-advances-in-the-pathophysiology-and-molecular-basis-of-sepsis-associated-organ-dysfunction-novel-therapeutic-implications-and-challenges
#15
REVIEW
Yuichi Hattori, Kohshi Hattori, Tokiko Suzuki, Naoyuki Matsuda
Sepsis is one of the most common reasons for critically ill patients to be admitted to an intensive care unit and, despite advances in overall medical care, it represents a major clinical problem and remains the leading cause of death in the critically ill patient population. Although sepsis has been defined as a systemic inflammatory syndrome, in which there is an identifiable focus of infection, clinical trials aimed at anti-inflammatory therapeutic approaches have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis...
February 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28232276/cannabidiol-state-of-the-art-and-new-challenges-for-therapeutic-applications
#16
REVIEW
Simona Pisanti, Anna Maria Malfitano, Elena Ciaglia, Anna Lamberti, Roberta Ranieri, Gaia Cuomo, Mario Abate, Giorgio Faggiana, Maria Chiara Proto, Donatella Fiore, Chiara Laezza, Maurizio Bifulco
Over the past years, several lines of evidence support a therapeutic potential of Cannabis derivatives and in particular phytocannabinoids. Δ(9)-THC and cannabidiol (CBD) are the most abundant phytocannabinoids in Cannabis plants and therapeutic application for both compounds have been suggested. However, CBD is recently emerging as a therapeutic agent in numerous pathological conditions since devoid of the psychoactive side effects exhibited instead by Δ(9)-THC. In this review, we highlight the pharmacological activities of CBD, its cannabinoid receptor-dependent and -independent action, its biological effects focusing on immunomodulation, angiogenetic properties, and modulation of neuronal and cardiovascular function...
February 20, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28232023/peptide-regulation-of-cofilin-activity-in-the-cns-a-novel-therapeutic-approach-for-treatment-of-multiple-neurological-disorders
#17
REVIEW
Alisa E Shaw, James R Bamburg
Cofilin is a ubiquitous protein which cooperates with many other actin-binding proteins in regulating actin dynamics. Cofilin has essential functions in nervous system development including neuritogenesis, neurite elongation, growth cone pathfinding, dendritic spine formation, and the regulation of neurotransmission and spine function, components of synaptic plasticity essential for learning and memory. Cofilin's phosphoregulation is a downstream target of many transmembrane signaling processes, and its misregulation in neurons has been linked in rodent models to many different neurodegenerative and neurological disorders including Alzheimer disease (AD), aggression due to neonatal isolation, autism, manic/bipolar disorder, and sleep deprivation...
February 20, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28223162/the-roles-of-histamine-and-its-receptor-ligands-in-central-nervous-system-disorders-an-update
#18
REVIEW
Weiwei Hu, Zhong Chen
The neurotransmitter histamine receives less attention compared with other biogenic amines, because of its moderate action in the central nervous system (CNS). However, recent evidence suggests that histamine plays an important role in multiple CNS disorders including insomnia, narcolepsy, Parkinson's diseases, schizophrenia, Alzheimer's disease, and cerebral ischemia. New insights are emerging into the potential roles of histamine receptors as targets for the treatment of these diseases. Although some histamine related agents have failed in clinical trials, current preclinical studies suggest that this neurotransmitter may still have extensive applications in treating CNS disorders, however, advanced studies are warranted...
February 20, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28216026/cyclic-nucleotide-imaging-and-cardiovascular-disease
#19
REVIEW
Filip Berisha, Viacheslav O Nikolaev
The universal second messengers cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) play central roles in cardiovascular function and disease. They act in discrete, functionally relevant subcellular microdomains which regulate, for example, calcium cycling and excitation-contraction coupling. Such localized cAMP and cGMP signals have been difficult to measure using conventional biochemical techniques. Recent years have witnessed the advent of live cell imaging techniques which allow visualization of these functionally relevant second messengers with unprecedented spatial and temporal resolution at cellular, subcellular and tissue levels...
February 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28216025/pi3k-akt-mtor-inhibitors-in-breast-cancers-from-tumor-cell-signaling-to-clinical-trials
#20
REVIEW
Dey Nandini, De Pradip, Leyland-Jones Brian
Breast cancer (BC) is the most common women cancer and second most common cause of cancer death in women. A woman living in the United States has 12.3% lifetime risk of being diagnosed with BC. From the genomics point of view, the most common three subtypes of BC encountered in clinics are HR+, HER2+, and TNBC or basal-like BC. Estrogen receptor (ER) status or HER2 amplification or chemotherapy is not sufficient to understand the underlying mechanisms of disease progression and resistance (de novo or acquire)...
February 16, 2017: Pharmacology & Therapeutics
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