Abstract:
:1. Erlotinib, a small-molecule epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, has been approved for the management of advanced non-small cell lung cancer. The aim of the present study was to investigate whether erlotinib exerts potent antitumour activities through the reactive oxygen species (ROS)-c-Jun N-terminal kinase (JNK) pathway in the human non-small cell lung cancer cell line A549. 2. The 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and Hoechst 33342 staining showed that erlotinib produced a decline in cell viability of A549 cells and induced cell apoptosis, coupled with quick accumulation of ROS. In addition, erlotinib increased the respiratory control ratio, NADPH oxidase catalytic subunit gp91(phox) expression and superoxide anion (O2(-)) generation, suggesting that erlotinib induced ROS production in A549 cells from both mitochondrial and NADPH oxidase sources. 3. Fluorescence microscopy with the JC-1 probe and western blot analysis indicated that erlotinib induced loss of mitochondrial membrane potential, the release of cytochrome c and apoptosis-inducing factor (AIF) and activation of JNK. 4. The results of the present study suggest that erlotinib has potent antitumour activity in A549 cells by activating ROS-dependent, JNK-driven cell apoptosis. These findings provide a novel insight into the mechanism of action of erlotinib in the treatment of human non-small cell lung cancer in addition to its effects in inhibiting EGFR-TK.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Qian X,Li J,Ding J,Wang Z,Zhang W,Hu Gdoi
10.1111/j.1440-1681.2008.05091.xsubject
Has Abstractpub_date
2009-05-01 00:00:00pages
487-94issue
5-6eissn
0305-1870issn
1440-1681pii
CEP5091journal_volume
36pub_type
杂志文章abstract::The currently available chemotherapeutic regimens against gastric cancer are not very effective, leading to high recurrence and poor survival. Resveratrol is a naturally occurring polyphenol with potent apoptosis-inducing activity. However, the mechanism underlying its actions remains unknown. In the present study, hu...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05660.x
更新日期:2012-03-01 00:00:00
abstract::Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes that catalyse the conversion between cis and trans conformations of proline imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms of cellular function and pathophysiology of disease. There are three different cla...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12335
更新日期:2015-02-01 00:00:00
abstract::1. Oxidative stress (OS) is a biological entity indicated as being responsible for several pathologies, including diabetes. Diabetes can also be associated with human cirrhosis. Portal hypertension (PH), a major syndrome in cirrhosis, produces hyperdynamic splanchnic circulation and hyperaemia. The present study was d...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.03963.x
更新日期:2004-03-01 00:00:00
abstract::1. Emotional stress is one of the aetiologies of cardiac accidents, but the precise mechanisms remain to be elucidated. In the present study we used the immobilization stress model in rats to investigate electrocardiographic (ECG) changes. 2. A rapid elevation of the ST segment at the II, III, aVF and precordial leads...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2000.03249.x
更新日期:2000-05-01 00:00:00
abstract::1. Patients with chronic kidney disease (CKD) demonstrate a high burden of vascular disease. This vascular disease is unusual by way of a preponderance of medial calcification. Further, traditional cardiovascular risk factors fail to fully explain the high cardiovascular event rate in this population. 2. The present r...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2007.04660.x
更新日期:2007-07-01 00:00:00
abstract::1. In the present study we have examined the effects of angiotensin I converting enzyme (ACE) inhibition and nitric oxide (NO) synthesis inhibition on bradykinin (BK) depressor responses in pregnancy in both Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Ramipril (10 mg/kg, i.v.) significantly reduce...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1995.tb02051.x
更新日期:1995-06-01 00:00:00
abstract::Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 μg once monthly for 2 mo...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/1440-1681.12618
更新日期:2016-10-01 00:00:00
abstract::Transthyretin (TTR) is a binding protein for the thyroid hormone thyroxine (T4 ), retinol and β-amyloid peptide. TTR aids the transfer of T4 from the blood to the cerebrospinal fluid (CSF), but also prevents T4 loss from the blood-CSF barrier. It is, however, unclear whether TTR affects the clearance of β-amyloid from...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12598
更新日期:2016-09-01 00:00:00
abstract::1. The use of non-linear dynamic analysis for the measurement of control processes in low-dimensional signals, for example, blood pressure and heart rate variability, are well established and accepted. However, the application of these analytical techniques to a high-dimensional signal, such as renal sympathetic nerve...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02340.x
更新日期:1998-11-01 00:00:00
abstract::1. Phytoncides are volatile substances released mainly from trees. We studied whether phytoncides can reduce stress responses in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Under the restraint stress, SHRSP exposed to phytoncides showed lower blood pressure than those without the exposure (186.8 +/- 3.9 v...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04102.x
更新日期:2004-12-01 00:00:00
abstract::Heart rate recovery (HRR) describes the rapid deceleration of heart rate after strenuous exercise and is an indicator of parasympathetic tone. A reduction in parasympathetic tone occurs in patients with congestive heart failure, resulting in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can e...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12773
更新日期:2017-08-01 00:00:00
abstract::1. Several selective antagonists are available to differentiate between muscarinic receptors. 2. Further subdivision of M1 and M2 muscarinic receptors appears possible and is supported by studies with cloned receptors. 3. Reasons for differences between affinity constants determined in functional and binding studies a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1989.tb01599.x
更新日期:1989-06-01 00:00:00
abstract::1. Endothelial dysfunction is seen in patients with essential hypertension or congestive heart failure (CHF). The present study aimed to evaluate the direct effect on endothelium- dependent vasodilation (EDV) of different pharmacological drugs commonly used in the treatment of these conditions. 2. Forearm blood flow (...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1440-1681.2001.03465.x
更新日期:2001-05-01 00:00:00
abstract::1. Over the past 50 years considerable evidence has been reported suggesting that endogenous opioids participate in the control of renal function. 2. Exogenous administration of opioids produces profound changes in the renal excretion of water and sodium. 3. Opioids produce changes in urine output and urine sodium exc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb02324.x
更新日期:1995-12-01 00:00:00
abstract::1. The aim of this study was to assess the vagal and sympathetic nerve contribution to the relationship between mean arterial pressure (MAP) and heart rate (HR) at 6, 9, 14 and 20 weeks of age in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with methoxamine- and nitroprusside-induced steady-s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01075.x
更新日期:1988-04-01 00:00:00
abstract::1. Oxidative stress plays a role in senescence-associated organ deterioration. This is supported by the beneficial effects of anti-oxidants against ageing-related organ damage, although their role in cardiac ageing has not been elucidated. 2. The aim of the present study was to examine the impact of cardiac-specific o...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04540.x
更新日期:2007-01-01 00:00:00
abstract::1. The aim of the present study was to perform an in vivo estimation of the Michaelis-Menten constants of the major metabolic pathways of paracetamol (APAP). 2. A two-occasion, single-dose cross-over trial was performed using 60 and 90 mg/kg doses of APAP in healthy patients undergoing third molar dental extraction. P...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05029.x
更新日期:2009-01-01 00:00:00
abstract::1. We investigated the effect of exercise on plasma adrenomedullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. T...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb01194.x
更新日期:1997-05-01 00:00:00
abstract::1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01538.x
更新日期:1989-03-01 00:00:00
abstract::This study aimed to evaluate the changes in left and right ventricular functions of children with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) and to determine the efficacy of surgical treatment for OSAHS in children. The subjects included 20 normal controls and 55 children of OSAHS with adenoid and/or tonsil h...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12408
更新日期:2015-06-01 00:00:00
abstract::1. The effects of ATP and some of its more stable analogues have been examined upon preparations of epididymal and prostatic halves of vasa deferentia and of cauda epididymides from rats that had undergone vasectomy by medial transection of the vas deferens. 2. After unilateral vasectomy, the potencies of ATP, beta, g...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1990.tb01358.x
更新日期:1990-08-01 00:00:00
abstract::Cardiac output and rhythm depend on the release and the take-up of calcium from the sarcoplasmic reticulum (SR). Excessive diastolic calcium leak from the SR due to dysfunctional calcium release channels (RyR2) contributes to the formation of delayed after-depolarizations, which underlie the fatal arrhythmias that occ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12669
更新日期:2017-01-01 00:00:00
abstract::1. It has previously been shown that perfusion with high O2-affinity-erythrocytes decreases venous PO2 (PVO2) and decreases O2 uptake (VO2) in contracting muscle at the same O2 delivery (arterial O2 concentration x flow). A linear VO2-PVO2 relationship has been obtained with a VO2-axis intercept, suggesting that, duri...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03100.x
更新日期:1999-08-01 00:00:00
abstract::1. The antinociceptive effect of prostaglandins E1, E2 and F2alpha was studied in albino rats. Though all three prostaglandins produced similar degrees of sedation, only prostaglandin E1 (PGE1) produced a dose-related antinociceptive activity. 2. The antinociceptive activities of equi-analgesic doses of morphine (7.5....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1977.tb02621.x
更新日期:1977-05-01 00:00:00
abstract::1. The ulcerogenesis of gastric haemorrhagic damage during sepsis is unclear. The present study first proposes that gastric haemorrhagic ulcer is modulated by mucosal glutathione, histamine and oxyradicals in lipopolysaccharide (LPS)-induced sepsis in rats. The protective effects of several drugs on the ulcerogenic pa...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2000.03241.x
更新日期:2000-04-01 00:00:00
abstract::1. Arterial baroreceptor denervation produces acute hypertension, but chronically denervated animals have an average arterial pressure that is similar to that of baroreceptor intact animals. 2. Although cardiopulmonary baroreceptors and renal compensations have been suggested to mediate the restoration of a normal ave...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1997.tb01787.x
更新日期:1997-01-01 00:00:00
abstract::1. Insulin-liposomes of four different lipid combinations were given intragastrically to normal rats on twenty occasions and to diabetic rats on 164 occasions. 2. Normal rats showed no hypoglycaemic response to either sonicated or unsonicated liposomes. 3. Diabetic rats failed to respond to sonicated liposomes but six...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1982.tb00819.x
更新日期:1982-07-01 00:00:00
abstract::1. The effects of the alpha-beta-adrenergic antagonist labetalol on the activation of human platelets by adrenaline and other aggregating stimuli have been investigated. 2. Labetalol inhibited platelet aggregation and secretion induced by collagen and the second phase of aggregation caused by ADP, platelet activating ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01099.x
更新日期:1988-06-01 00:00:00
abstract::Urinary levels of glycosaminoglycans (GAG) and hydroxyproline from normal and fluoride treated rabbits were estimated. The hydroxylysine content of serum and urine of rabbits after excessive ingestion of fluoride was also investigated. There was a progressive decrease in GAG content, reduction in hydroxylysine, wherea...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1983.tb00231.x
更新日期:1983-09-01 00:00:00
abstract::1. The effects of left ventricular repair (LVR) surgery for ischaemic or dilated cardiomyopathy are not fully understood. The development of a proper animal model will help to resolve this issue. 2. The ischaemic cardiomyopathy (ICM) model used was as follows. Twenty-six rats developed ICM with a large akinetic left v...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03708.x
更新日期:2002-08-01 00:00:00