Abstract：
:Cancer immunotherapies are dramatically reshaping the clinical management of oncologic patients. For many of these therapies, the guidelines for administration, monitoring, and management of associated toxicities are still being established. This is especially relevant for adoptively transferred, genetically-modified T cells, which have unique pharmacokinetic properties, due to their ability to replicate and persist long-term, following a single administration. Furthermore, in the case of CAR-T cells, the use of synthetic immune receptors may impact signaling pathways involved in T cell function and survival in unexpected ways. We, herein, comment on the most salient aspects of CAR-T cell design and clinical experience in the treatment of solid tumors. In addition, we discuss different possible scenarios for combinations of CAR-T cells and other treatment modalities, with a special emphasis on kinase inhibitors, elaborating on the strategies to maximize synergism. Finally, we discuss some of the technologies that are available to explore the molecular events governing the success of these therapies. The young fields of synthetic and systems biology are likely to be major players in the advancement of CAR-T cell therapies, providing the tools and the knowledge to engineer patients' T lymphocytes into intelligent cancer-fighting micromachines.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Ramello MC,Haura EB,Abate-Daga Ddoi
10.1016/j.phrs.2017.11.035subject
Has Abstractpub_date
2018-03-01 00:00:00pages
194-203eissn
1043-6618issn
1096-1186pii
S1043-6618(17)30600-Xjournal_volume
129pub_type
杂志文章abstract：:The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibite...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1998.0398
更新日期：1998-12-01 00:00:00
abstract：:The cytokine thymic stromal lymphopoietin (TSLP) is involved in the development and the progression of allergic diseases. It is mainly released by epithelial cells at barriers such as skin and gut in response to danger signals. Overexpression of TSLP in keratinocytes (KC) can provoke the development of a type 2 inflam...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.08.001
更新日期：2016-11-01 00:00:00
abstract：:The effects of trans-resveratrol (RSV) combined with ethanol (EtOH) were evaluated by (31)P NMR on total ATP and sn-glycerol-3-phosphate (sn-G3P) contents measured in real time in isolated and perfused whole liver of the rat. Mitochondrial ATP turnover was assessed by using specific inhibitors of glycolytic and mitoch...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2011.12.003
更新日期：2012-03-01 00:00:00
abstract：:This paper describes a new sensitive gas chromatographic method with electron capture detector to assay estazolam in human plasma, which has been developed and validated for pharmacokinetic purposes. The drug and the internal standard (triazolam) were extracted from plasma buffered at pH 9.0 into toluene and analysed ...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1006/phrs.1997.0144
更新日期：1997-04-01 00:00:00
abstract：:Pre-eclampsia (PE) is a complication of pregnancy that is associated with mortality and morbidity in mothers and fetuses worldwide. Oxygen dysregulation in the placenta, abnormal remodeling of the spiral artery, defective placentation, oxidative stress at the fetal-maternal border, inflammation and angiogenic impairme...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104692
更新日期：2020-05-01 00:00:00
abstract：:We investigated the anti-platelet effect of a newly synthesized guanidine derivative KR-32560, a sodium/hydrogen exchanger-1 (NHE-1) inhibitor, together with the elucidation of the possible mode of action. KR-32560 concentration dependently inhibited the aggregation of washed rabbit platelets induced by collagen (10 m...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2005.12.003
更新日期：2006-03-01 00:00:00
abstract：:Dyslipidemia and hyperglycemia are associated with an increased risk of ischemic cardiovascular disease. Positive effects of a nutraceutical combination comprising red yeast rice, berberine, policosanol, astaxanthin, coenzyme Q10 and folic acid (NComb) on plasma lipid and glucose levels have been reported in some but ...
journal_title：Pharmacological research
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.phrs.2016.04.021
更新日期：2016-08-01 00:00:00
abstract：:In the last few years, exciting properties have emerged regarding the activation, signaling, mechanisms of action, and therapeutic targeting of the two types of neurotrophin receptors: the p75NTR with its intracellular and extracellular peptides, the Trks, their precursors and their complexes. This review summarizes t...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.04.024
更新日期：2017-07-01 00:00:00
abstract：:Mitochondria are best known for their role in ATP generation. However, studies over the past two decades have shown that mitochondria do much more than that. Mitochondria regulate both necrotic and apoptotic cell death pathways, they store and therefore coordinate cellular Ca2+ signaling, they generate and metabolize ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.08.010
更新日期：2018-12-01 00:00:00
abstract：:Stem cell mediated cardiac repair is an exciting and controversial area of cardiovascular research that holds the potential to produce novel, revolutionary therapies for the treatment of heart disease. Extensive investigation to define cell types contributing to cardiac formation, homeostasis and regeneration has prod...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.06.007
更新日期：2018-01-01 00:00:00
abstract：:Kidney injury is one of the main complications of obstructive jaundice (OJ) and its pathogenesis has not been clarified. As an independent risk factor for OJ associated with significant morbidity and mortality, it can be mainly divided into two types of morphological injury and functional injury. We called these dysfu...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.105311
更新日期：2021-01-01 00:00:00
abstract：:Treatment of MC3T3E-1 osteoblast cultures with combined interferon- gamma(IFN- gamma), lipopolysaccharide (LPS) and tumor necrosis factor- alpha(TNF- alpha) induces expressions of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), resulting in sustained releases of large amounts of nitric oxide and IL-6....
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0778
更新日期：2001-03-01 00:00:00
abstract：:DB-67 and its lactone homolog DB-91 are derivatives of topoisomerase I inhibitor camptothecin (CPT) with silyl moiety, which may exhibit a slower inactivation process by changed kinetics of protein binding and/or hydrolysis of its lactone ring and result in increased antitumor activity and decreased toxicity. Pharmaco...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2009.07.005
更新日期：2010-02-01 00:00:00
abstract：:Psoriasis is a lifelong, chronic and immune-mediated skin disease affecting approximately 1-3% of the Caucasian population. Pathogenesis of psoriasis is associated with an increased expression of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a pro-inflammatory cytokine and important mediator of cachexia. Anti-...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2008.02.006
更新日期：2008-04-01 00:00:00
abstract：:Male weanling Wistar rats were fed a 4% cholestyramine diet and used as a model to demonstrate that a reduction in serum low density lipoproteins stimulates de novo cholesterogenesis leading to DNA synthesis and cell proliferation. Feeding this diet resulted in a decrease in serum very low density lipoproteins and low...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(89)90195-3
更新日期：1989-09-01 00:00:00
abstract：:Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion (I/R) injury of various organs. Sulforaphane is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. In this study, we investigated whether sulforaphane protects heart against I/R ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2009.11.009
更新日期：2010-04-01 00:00:00
abstract：:Protein kinase C (PKC) is a family of kinases that are critical in many cellular events. These enzymes are activated by lipid-derived second messengers, are dependent on binding to negatively charged phospholipids and some members also require calcium to attain full activation. The interaction with lipids and calcium ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2007.04.014
更新日期：2007-06-01 00:00:00
abstract：:The anti-inflammatory effect of glucocorticoids depends, at least in part, on the induction of two regulatory proteins, lipocortin and vasocortin, both preventing the release of inflammatory mediators. Lipocortin inhibits phospholipase A2 (PLA2) and therefore reduces arachidonic acid metabolites formation. Vasocortin ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/s1043-6618(05)80058-1
更新日期：1992-01-01 00:00:00
abstract：:Folic acid-conjugated albumin nanospheres (FA-AN) have been developed to provide an actively targetable drug delivery system for improved drug targeting of cancer cells with reduced side effects. The nanospheres were prepared by conjugating folic acid onto the surface of albumin nanospheres using 1-ethyl-3-(3-dimethyl...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2010.10.012
更新日期：2011-01-01 00:00:00
abstract：:Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2006.09.009
更新日期：2007-01-01 00:00:00
abstract：:We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological condi...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章
doi：10.1006/phrs.2000.0709
更新日期：2000-10-01 00:00:00
abstract：:The natural resin collected from the trunk wood of Protium heptaphyllum is used in folk medicine to treat inflammatory conditions and to hasten wound repair. In the search of new potential anti-inflammatory agents with gastroprotective property, the present study evaluated its effects in experimental models of gastric...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2003.09.001
更新日期：2004-02-01 00:00:00
abstract：:Recent studies have shown that a higher consumption of green tea leads to a lower prevalence of depressive symptoms in elderly individuals. However, no studies have explored the antidepressant-like effect of green tea in preclinical models of depression. The aim of this study was to investigate the antidepressant-like...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2011.09.007
更新日期：2012-01-01 00:00:00
abstract：:Extrasynaptically located γ-aminobutyric acid (GABA) receptors type A are often characterized by the presence of a δ subunit in the receptor complex. δ-Containing receptors respond to low ambient concentrations of GABA, or respond to spillover of GABA from the synapse, and give rise to tonic inhibitory currents. In ce...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.05.014
更新日期：2016-09-01 00:00:00
abstract：:Cardiac intracellular Na+and Ca2+homeostasis is regulated by the concerted action of ion channels, pumps and exchangers. The Na+, K+-ATPase produces the electrochemical concentration gradient for Na+, which is the driving force for Ca2+removal from the cytosol via the Na+/Ca2+exchange. Reduction of this gradient by in...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1998.0416
更新日期：1999-03-01 00:00:00
abstract：:Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. inc...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2013.09.008
更新日期：2013-12-01 00:00:00
abstract：:CHF5074 is a non-steroidal anti-inflammatory derivative holding disease-modifying potential for the treatment of Alzheimer's disease. The aim of the present study was to characterize the electrophysiological and metabolic profile of CHF5074 in the hippocampus. Electrophysiological recordings show that CHF5074 inhibits...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2014.02.010
更新日期：2014-03-01 00:00:00
abstract：:Cancer immunotherapy has come of age with the advent of immune checkpoint inhibitors. In this article we review how agonists for receptors of the innate immune system, the Toll-like receptors and the RIG-I-like receptors, impact anticancer immune responses. Treatment with these agonists enhances the activity of antica...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.03.001
更新日期：2020-04-01 00:00:00
abstract：:Several studies on disease and treatment effects on neurohormones have been conducted with small numbers of patients, using one blood sample as representative of their states. The aim of this study was to assess the within-patient variability of plasma concentrations of several hormones and cytokines of recent interes...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章
doi：10.1006/phrs.1998.0288
更新日期：1998-03-01 00:00:00
abstract：:As the body's first line of defense, the skin is the organ most frequently exposed to chemicals present in personal hygiene products, household products, or materials used in the work environment. In this context, skin disorders account for more than 40 % of all occupational and work-related diseases, constituting a s...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105282
更新日期：2020-12-01 00:00:00
