Abstract:
:No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) to date. Since HCC is one of the hypervascular solid tumors, blocking angiogenesis represents an intriguing approach to HCC chemoprevention. The aim of the current study was to examine the combined effect of the anti-angiogenic agents: leflunomide; a disease modifying antirheumatic drug, perindopril; an angiotensin converting enzyme inhibitor (ACEI) and curcumin; the active principle of turmeric, on diethylnitrosamine (DEN)-induced HCC in mice. Eight weeks following DEN administration, there was a significant rise in immunohistochemical staining of CD31-positive endothelial cells and consequently hepatic microvessel density (MVD) as compared to normal liver. DEN treatment was associated with elevation in hepatic vascular endothelial growth factor (VEGF) level as compared to normal controls (P<0.05, 3842±72pg/ml and 2520.8±97pg/ml, respectively). Similarly, increased hepatic expression of hypoxia inducible growth factor-1α (HIF-1α) was observed in 100% of the DEN-treated animals compared to 0% in their normal counterparts. Treatment with leflunomide, perindopril or curcumin alone abrogated the DEN-induced increased MVD as well as the elevated expression of VEGF, while only curcumin inhibited HIF-1α hepatic expression. Combination of these agents showed further inhibitory action on neovascularization and synergistic attenuation of hepatic VEGF (1954.27±115pg/ml) when compared to each single agent. Histopathological examination revealed a more beneficial chemopreventive activity in the combination group compared to each monotherapy. In conclusion, the combination treatment of leflunomide, perindopril and curcumin targeting different angiogenic pathways, resulted in synergistic inhibition of angiogenesis and consequently more effective chemoprevention of HCC.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Nasr M,Selima E,Hamed O,Kazem Adoi
10.1016/j.ejphar.2013.11.022subject
Has Abstractpub_date
2014-01-15 00:00:00pages
267-75eissn
0014-2999issn
1879-0712pii
S0014-2999(13)00894-7journal_volume
723pub_type
杂志文章abstract::The effect of resveratrol, an aryl hydrocarbon receptor antagonist, on the teratogenicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated. Pregnant C57BL/6J mice were orally administered resveratrol (50 mg/kg) for 6 consecutive days, from gestational day (GD) 8 to GD13, followed by an oral chall...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.05.033
更新日期:2008-09-04 00:00:00
abstract::The nerve growth factor (NGF) is a neurotrophic factor essential for the development and survival of neurons. It has also been identified as a mediator of inflammation and can cause airway hyperresponsiveness [Frossard et al., Eur. J. Pharmacol. 500, 453 (2004)]. Evidence in rodents suggests a link between tachykinins...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.10.068
更新日期:2007-04-10 00:00:00
abstract::Opioid antagonists, naloxone and naltrexone have long been used in clinical practice and research. In addition to their low selectivity, they easily pass through the blood-brain barrier. Quaternization of the amine group in these molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In addition, zw...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.05.024
更新日期:2017-08-15 00:00:00
abstract::Oxyntomodulin, a hormone released from jejuno-ileum and composed of the glucagon sequence extended by a C-terminal octapeptide displays original tissue specificity for the gastric mucosa. The aim of this study was to compare the effect of oxyntomodulin on histamine (0.4 mg/kg per h)-stimulated gastric acid secretion i...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90720-b
更新日期:1991-10-15 00:00:00
abstract::The effect of antiepileptic drug di-n-propylacetamide (DPM) on 5-hydroxytryptamine (5-HT) turnover in rat brain and 5-hydroxyindoleacetic acid (5-HIAA) in cat cerebrospinal fluid (CSF) was investigated. DPM (200 mg/kg) increased brain 5-HIAA without altering the 5-HT level. DPM augmented the accumulation of 5-HT induc...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90361-8
更新日期:1983-07-15 00:00:00
abstract::We have developed a model of ischaemia-reperfusion injury in C57BL/6 mice involving ischaemia for 0.5 to 2.5 h with an elastic tourniquet on one hind limb and reperfusion for 24 h, analogous to a well-established model of ischaemia-reperfusion injury in the rat. Viability was assessed in tissue homogenates of the gast...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01101-1
更新日期:1997-08-13 00:00:00
abstract::The effect of intracutaneous adrenaline and noradrenaline (5 X 10(-12) and 5 X 10(-11) mol) was examined on the oedema (Evans blue dye leakage) response of rats to several inflammatory agents. The catecholamines reduced the oedema response to all agents tested except prostaglandin E1 (PGE1) which was significantly pot...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(79)90500-4
更新日期:1979-08-15 00:00:00
abstract::Using 3H-ligands and radioactive microspheres we studied the binding characteristics and the effects on the distribution of carotid arterial blood flow of n-(3-acetylaminophenyl)piperazine hydrochloride (BEA 1654). The compound had a Ki value of 32 nM (5-HT: 8 nM) on 5-HT1 but no or very weak affinity for 5-HT2, alpha...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90259-6
更新日期:1985-01-08 00:00:00
abstract::We have reported previously that the dipeptidyl peptidase IV inhibitor Ile-Pro-Ile had an antihyperalgesic action in rats when given intrathecally in the carrageenan-induced hyperalgesia, as detected by the Randall-Selitto test. Vildagliptin, a non-peptide inhibitor of the same enzyme, which is already on the market a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.09.060
更新日期:2011-01-10 00:00:00
abstract::It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.03.006
更新日期:2016-04-15 00:00:00
abstract::A series of potent bombesin antagonists based on the reduced C-terminal peptide bond modification which in the past resulted in the first really potent antagonists are compared for effects on bombesin-stimulated amylase release from and binding to rat and guinea pig pancreatic acini. It was found that the original mem...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)94109-b
更新日期:1990-11-06 00:00:00
abstract::The present study was undertaken to investigate the involvement of chemical mediators in nasal allergic responses using histidine decarboxylase knockout (HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and pertuss...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.01.082
更新日期:2007-07-19 00:00:00
abstract::Levetiracetam ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide, ucb L059) is a novel potential antiepileptic agent presently in clinical development with unknown mechanism of action. The finding that its anticonvulsant activity is highly stereoselective (Gower et al., 1992) led us to investigate the presence of specific b...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00436-o
更新日期:1995-11-14 00:00:00
abstract::Food intake is regulated by various factors such as neuropeptide Y. Neuropeptide Y potently induces an increase in food intake, and simultaneously stimulates arginine-vasopressin (AVP) secretion in the brain. Recently, we reported that V(1A) vasopressin receptor-deficient (V(1A)R(-/-)) mice exhibited altered daily foo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.09.017
更新日期:2009-11-10 00:00:00
abstract::Acid sensing ion channels (ASICs) are implicated in various brain functions including learning and memory and are involved in a number of neurological disorders such as pain, ischemic stroke, depression, and multiple sclerosis. We have recently defined ASICs as one of receptor targets of aromatic diamidines in neurons...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2010.09.005
更新日期:2010-12-01 00:00:00
abstract::Recombinant human tumor necrosis factor alpha (TNF alpha) decreases social exploration and induces weight loss in mice in a dose- and time-dependent manner (2.5-40 micrograms/mouse). To assess the role of interleukin-1 (IL-1) in these effects, mice pretreated with IL-1 receptor antagonist (IL-1ra, 500 micrograms/mouse...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90184-r
更新日期:1991-12-17 00:00:00
abstract::Cholangiocarcinoma (CCA) is one of the most serious of all cancers and a major public health problem. CCA is an extremely invasive cancer, and the survival rate for CCA patients is only 24 months after diagnosis. Although surgery and chemotherapy can extend the survival rate to 5 years, < 20-40% of CCA patients will s...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.09.023
更新日期:2018-11-15 00:00:00
abstract::Previous studies with both intact cells and ram seminal vesicles microsomes have shown that the specific PGHS-2 inhibitors NS-398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulfonamide) and DuP-697 (5-bromo-2[4-fluorophenyl]-3-[4-methylsulfonylphenyl]-thiophene) attenuate the inhibition of PGHS-1 caused by aspirin and...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02450-0
更新日期:2002-10-25 00:00:00
abstract::Administration of methyl-beta-carboline-3-carboxamide (FG 7142, 15 mg/kg i.p.) to rats has previously been shown to cause a selective increase in the levels of 3,4-dihydroxy-phenylacetic acid (DOPAC) in the prefrontal cortex and ventral tegmental area (VTA) via an interaction with benzodiazepine receptors. On withdraw...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90221-4
更新日期:1987-06-04 00:00:00
abstract::The aim of our review is to summarize common genetic variations of some receptors associated with clinical consequences, which were not outlined in the previous special issue of this journal. Because of the multiple pathomechanisms of diseases, a set of genetic variation can play a role in the development of pathologi...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0014-2999(01)00755-5
更新日期:2001-02-23 00:00:00
abstract::Free radicals may cause part of the irreversible injury which occurs during myocardial infarction and reperfusion. In the present study MDL 73404, an alpha-tocopherol analogue which is a free radical scavenger has been evaluated for its effects on infarct size in an anaesthetised rat model of coronary artery ligation ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90655-n
更新日期:1992-01-07 00:00:00
abstract::The areas S of the ventral surface of the brain stem and the immediately surrounding zone were superficially destroyed by the means of electro-coagulation, in 14 cats. This destruction produced a drop in blood pressure, which was transient in 9 and definitive in 4 animals; in one cat only the arterial pressure did not...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(75)90235-6
更新日期:1975-11-01 00:00:00
abstract::We have reported previously that ugonin K, a flavonoid isolated from Helminthostachys zeylanica (L.) Hook, potently induces cell differentiation and mineralization of MC3T3-E1 mouse osteoblast-like cells. Here we aimed to elucidate whether ugonin K evoked osteogenesis required interaction with estrogen receptor. Resul...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.12.001
更新日期:2012-02-15 00:00:00
abstract::It has been shown that inflammation of rat paws elicits accumulation of opioid peptide beta-endorphin-containing immune cells in the inflamed subcutaneous tissue, contributing to immunocyte-produced pain suppression. However, the possible mechanisms involved in the pharmacological application of beta-endorphin in rat ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.08.012
更新日期:2006-11-07 00:00:00
abstract::The effect of KC 2450 (racemic 3,5-cis-3-methylamino-2,3,4,5-tetrahydro-1-benzoxepine-5-ol hydrochloride) on lower esophageal sphincter pressure in pentobarbital-anesthetized dogs was determined and compared to the effect of metoclopramide. The ED20 value (i.e. the dose that increased lower esophageal sphincter pressu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(87)90111-7
更新日期:1987-10-13 00:00:00
abstract::Lung cancer is a disease with increasing morbidity worldwide in recent years. Approaches such as chemotherapy and biological targeting for its treatment are urgently needed. Epithelial-mesenchymal transition (EMT) is an important initiation stage for tumor cells to acquire invasive and metastatic abilities. Increasing...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172630
更新日期:2019-11-05 00:00:00
abstract::Rats were treated with 10 mg/kg tetrahydroaminoacridine (THA) twice daily for 14 days. THA (10 mg/kg) induced a significant decrease in the number of muscarinic receptors (both M1 and M2) in the cortex and striatum, whereas the number of nicotinic receptors in the cortex and hippocampus increased. Rats treated with ph...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90448-f
更新日期:1990-09-21 00:00:00
abstract::Many central stimulating drugs have a pronounced stimulatory effect on striatal and cortical activity which is associated to enhanced function of mesencephalic dopaminergic neurons. Mesencephalic KCNQ (also termed K(v)7) potassium channels suppress the basal activity of dopaminergic neurons in the substantia nigra and...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.05.029
更新日期:2007-09-10 00:00:00
abstract::Increasing evidence displays that microRNAs (miRNAs) participate in the development of various human malignancies, including esophageal squamous cell carcinoma (ESCC). MicroRNA-33a-5p (miR-33a-5p) has recently been reported to function as a tumor suppressor in many human cancers. However, the expression and role of mi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172590
更新日期:2019-10-15 00:00:00
abstract::Itching is known as a commonly side effect of opioid administration. However, the relationship of opioid receptors to itching is unclear. In this study, we examined the effect of intradermal injection of morphine and fentanyl on the itching sensation. When injected intradermally into the rostral back of mice, morphine...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.10.066
更新日期:2010-02-10 00:00:00