Abstract：
BACKGROUND AND PURPOSE:Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis. EXPERIMENTAL APPROACH:To elucidate the role of caspase-8 in lung carcinoma, we used human samples of non-small cell lung cancer (NSCLC) and a mouse model of carcinogen-induced lung cancer. KEY RESULTS:Healthy and cancerous NSCLC samples had similar levels of the active form of caspase-8. Similarly, lung tumour-bearing mice had high levels of the active form of caspase-8. Pharmacological inhibition of caspase-8 by z-IETD-FMK robustly reduced tumour outgrowth and this was closely associated with a reduction in the release of pro-inflammatory cytokines, IL-6, TNF-α, IL-18, IL-1α, IL-33, but not IL-1β. Furthermore, inhibition of caspase-8 reduced the recruitment of innate suppressive cells, such as myeloid-derived suppressor cells, but not of regulatory T cells to lungs of tumour-bearing mice. However, despite the well-known role of caspase-8 in cell death, the apoptotic cascade (caspase-3, caspase-9 and Bcl-2 dependent) was not active in lungs of z-IETD-treated tumour-bearing mice, but instead higher levels of the short segment of c-FLIP (c-FLIPs) were detected. Similarly, human healthy lung samples had higher levels of c-FLIPs than cancerous samples. CONCLUSIONS AND IMPLICATIONS:Our data suggest that caspase-8 is an important orchestrator of cancer-associated inflammation and the presence of short segment of c-FLIP determines whether caspase-8 induces tumour proliferation or tumour arrest/regression in the lung.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Terlizzi M,Di Crescenzo VG,Perillo G,Galderisi A,Pinto A,Sorrentino Rdoi
10.1111/bph.13176subject
Has Abstractpub_date
2015-08-01 00:00:00pages
3917-28issue
15eissn
0007-1188issn
1476-5381journal_volume
172pub_type
杂志文章abstract：:Strips of human pulmonary arteries from patients undergoing surgery for lung tumour were incubated with [3H]-noradrenaline. Subsequently, they were superfused with physiological salt solution containing cocaine and corticosterone. Tritium overflow from the strips was stimulated by transmural electrical impulses (2 Hz)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb11094.x
更新日期：1985-08-01 00:00:00
abstract：:1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb06985.x
更新日期：1977-01-01 00:00:00
abstract：:1. Nine non-steroidal anti-inflammatory drugs were tested for antagonism of bradykinin-induced bronchoconstriction in guinea-pig lungs in vivo. Only one, benzydamine, was inactive.2. The descending order of potency of the active anti-inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1968.tb07952.x
更新日期：1968-09-01 00:00:00
abstract：:The antioestrogen, tamoxifen, blocks volume-regulated chloride channels and reduces transparency in bovine lenses maintained in vitro. In contrast to tamoxifen, the steroidal antioestrogen, ICI 182780, did not block volume-regulated chloride currents in three cultured cell lines and required 10 fold higher concentrati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16622.x
更新日期：1995-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The age-related decline in vasorelaxation is largely due to ceramide-induced induction of phosphatase 2A (PP2A), which limits nitric oxide synthase (eNOS) phosphorylation at stimulatory sites. We hypothesized that ceramide accumulation was from an age-related loss of endothelial glutathione (GSH)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.28
更新日期：2008-04-01 00:00:00
abstract：:1. The role played by endogenous lipocortin 1 in the anti-migratory action exerted by dexamethasone (Dex) on monocyte recruitment in an in vivo model of acute inflammation was investigated by use of several neutralizing polyclonal antibodies raised against lipocortin 1 or a lipocortin 1-derived N-terminus peptide (pep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701029
更新日期：1997-03-01 00:00:00
abstract：:1. We examined the effect of the sulphonylurea glimepiride on three types of recombinant ATP-sensitive potassium (K(ATP)) channels. 2. K(ATP) channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart and SUR2B in smooth mus...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704062
更新日期：2001-05-01 00:00:00
abstract：:1 The rectum isolated from the fowl was perfused with Tyrode solution via the caudal mesenteric artery. Noradrenaline and adrenaline were biologically or fluorimetrically assayed in perfusates collected before and during stimulation of Remak's nerve or of the periarterial nerves.2 Perfusates collected during nerve sti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb07827.x
更新日期：1979-02-01 00:00:00
abstract：:1. Previous patch clamp studies of oesophageal circular muscle cells showed that nitric oxide (NO) modulated the opening of Ca2(+)-activated K+ channels involved in mediating the inhibitory junction potentials (i.j.ps). This study clarified the role of Ca2+ release from the superficial sarcoplasmic reticulum (SR) in t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15661.x
更新日期：1996-08-01 00:00:00
abstract：:1. The present study was designed to test the hypothesis that beneficial effects of angiotensin converting enzyme (ACE)inhibitors are independent of a fall in blood pressure in rat experimental heart failure following coronary ligation. 2. The animals were assigned randomly to six groups; sham operation, controls subj...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13155.x
更新日期：1994-07-01 00:00:00
abstract：:1. Sabcomeline (SB-202026, 0.03 mg kg(-1), p.o.), a potent and functionally selective M1 receptor partial agonist, caused a statistically significant improvement in the performance of a visual object discrimination task by marmosets. No such improvement was seen after RS86 (0.1 mg kg(-1), p.o.). 2. Initial learning, w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701844
更新日期：1998-05-01 00:00:00
abstract：:1. The fall in arterial blood pressure with bradycardia that occurs on injection of clonidine into the cerebral ventricles and into the cisterna magna is attributed to an action on ;chemosensitive zones' situated at the ventral surface of the brain stem. This conclusion is based on the following results obtained in ca...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08532.x
更新日期：1973-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1476-5381.2011.01620.x
更新日期：2012-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) metabolizes compounds containing catechol structures and has two forms: soluble (S-COMT) and membrane-bound (MB-COMT). Here we report the generation of a mouse line that expresses MB-COMT but not S-COMT. We compared the effects of deleting S-COMT only or both C...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00494.x
更新日期：2009-12-01 00:00:00
abstract：:The releases of [3H]5-hydroxytryptamine ([3H]5-HT) and of endogenous glutamic acid and their modulation through presynaptic h5-HT1B autoreceptors and h5-HT1D heteroreceptors have been investigated in synaptosomal preparations from fresh neocortical samples obtained from patients undergoing neurosurgery. The inhibition...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702336
更新日期：1999-02-01 00:00:00
abstract：:1 Prolonged exposure (6-12 h) of rat aorta to alpha1-adrenergic receptor (alpha(1)AR) agonist phenylephrine (Phe) leads to a decrease in alpha(1)AR-mediated vasoconstriction. This reduced responsiveness to alpha(1)AR stimulation was strongly dependent on the intactness of the endothelium. 2 We examined the effect of P...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706177
更新日期：2005-05-01 00:00:00
abstract：:1 A 3 min intracoronary infusion of adenosine (50 mug/min) produced a significant decrease in coronary artery perfusion pressure, left ventricular systolic pressure and myocardial O2 consumption in the isolated supported heart preparation of the dog perfused at a constant coronary blood flow. Heart rate was controlled...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1976.tb07681.x
更新日期：1976-07-01 00:00:00
abstract：:1. We have shown earlier that pilocarpine strongly inhibits mouse and human liver coumarin 7-hydroxylase activity of CYP 2A and pentoxyresorufin O-deethylase activity of CYP 2B in vitro. Since pilocarpine, like coumarin, contains a lactone structure we have studied in more detail its inhibitory potency on mouse and hu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb17217.x
更新日期：1995-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The human prostacyclin receptor (hIP), a G-protein coupled receptor (GPCR) expressed mainly on platelets and vascular smooth muscle cells, plays important protective roles in the cardiovascular system. We hypothesized that significant insights could be gained into the structure and function of th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707413
更新日期：2007-10-01 00:00:00
abstract：:1. Experiments were designed to determine whether endothelium-dependent relaxing factor(s) released by acetylcholine from the canine femoral artery influences the membrane potential of coronary arterial smooth muscle. 2. The membrane potential was recorded in small canine coronary arteries (internal diameter less than...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb10306.x
更新日期：1988-03-01 00:00:00
abstract：:1. The responses of bladder strips from control, streptozotocin-diabetic, and sucrose-drinking rats to electrical field stimulation were investigated. Sucrose-drinking rats were included as additional controls because they have enlarged bladders as a result of non-diabetic diuresis. 2. Bladder strips from diabetic rat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb16193.x
更新日期：1994-09-01 00:00:00
abstract：:Little is known about the intracellular actions of imipramine (IMI) in the regulation of ion channels. We tested the action of IMI on the intracellular cascade that regulates M current (I(M)) in superior cervical ganglion neurones (SCGs). Dialysis of the cells with GDPbetaS, a G protein signaling blocker, did not disr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706239
更新日期：2005-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II . As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascula...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13172
更新日期：2015-08-01 00:00:00
abstract：:1. Contraction of the rabbit isolated saphenous vein is mediated by a heterogeneous endothelin (ET) receptor population. This study has characterized these receptor subtypes by use of several pharmacologically distinct ET receptor agonists and antagonists. 2. ET-1, ET-3, sarafotoxin S6c (STXc) and [Ala3,11]ET-1 produc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb14936.x
更新日期：1995-04-01 00:00:00
abstract：:1. The effects of 1,3-di(2-tolyl)guanidine (DTG) were examined on the responses of cultured hippocampal neurones to the excitatory amino acid analogues N-methyl-D-aspartate (NMDA), kainate, quisqualate and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). 2. In rat hippocampal neurones loaded with the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13749.x
更新日期：1993-08-01 00:00:00
abstract：:1. Although extensively investigated, the extent of differences between receptors mediating negative inotropic and chronotropic responses is still unclear. In the present study atrial and intestinal muscarinic receptors were identified by [3H]-N-methyl-scopolamine ([3H]-NMS) binding and the affinities of some presumab...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11987.x
更新日期：1989-06-01 00:00:00
abstract：:1 The effect of intrarenal histamine, dimaprit (H2-agonist) and 2-(2-pyridyl) ethylamine (H1-agonist) on renin release was examined in anaesthetized dogs. 2 In dogs with intact kidneys, histamine and dimaprit administration resulted in renal vasodilatation, a two fold increase in urinary sodium excretion, and no chang...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10495.x
更新日期：1983-05-01 00:00:00
abstract：:1. Chronic administration of the benzodiazepine inverse agonist FG 7142 has previously been shown to induce seizure activity in mice. In the present study we have investigated the effects of acute and chronic treatment with FG 7142 in mice on the levels of acetylcholinesterase activity in cortex, hippocampus, midbrain...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14127.x
更新日期：1990-11-01 00:00:00
abstract：:1. Regulation of the increase in inositol-1,4,5-trisphosphate (IP3) production and intracellular Ca2+ concentration ([Ca2+]i by protein kinase C (PKC) was investigated in canine cultured tracheal smooth muscle cells (TSMCs). Stimulation of TSMCs by 5-hydroxytryptamine (5-HT) caused an initial transient [Ca2+]i peak fo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701195
更新日期：1997-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01391.x
更新日期：2011-09-01 00:00:00
