Abstract:
:Chemotherapy resistance is a major contributor to poor treatment responses and tumour relapse, the development of which has been strongly linked to the action of cancer stem cells (CSCs). Mounting evidence suggests that CSCs are reliant on low oxygen conditions and hypoxia-inducible factors 1α and 2α (HIF1α and HIF2α) to maintain their stem cell features. Research in the last decade has begun to clarify the functional differences between the two HIFα subtypes (HIFαs). Here, we review and discuss these differences in relation to CSC-associated drug resistance. Both HIFαs contribute to CSC survival but play different roles -HIF1α being more responsible for survival functions and HIF2α for stemness traits such as self-renewal - and are sensitive to different degrees of hypoxia. Failure to account for physiologically relevant oxygen concentrations in many studies may influence the current understanding of the roles of HIFαs. We also discuss how hypoxia and HIFαs contribute to CSC drug resistance via promotion of ABC drug transporters Breast cancer resistance protein (BCRP), MDR1, and MRP1 and through maintenance of quiescence. Additionally, we explore the PI3K/AKT cell survival pathway that may support refractory cancer by promoting CSCs and activating both HIF1α and HIF2α. Accordingly, HIF1α and HIF2α inhibition, potentially via PI3K/AKT inhibitors, could reduce chemotherapy resistance and prevent cancer relapse.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Schöning JP,Monteiro M,Gu Wdoi
10.1111/1440-1681.12693subject
Has Abstractpub_date
2017-02-01 00:00:00pages
153-161issue
2eissn
0305-1870issn
1440-1681journal_volume
44pub_type
杂志文章,评审abstract::1. The effect of endothelin-1 on the release of adrenal catecholamines was examined in anaesthetized dogs. 2. Splanchnic nerve stimulation (SNS) at 1 and 3 Hz was applied before and after the intravenous injection of endothelin-1. 3. Endothelin-1 (0.1 and 0.3 micrograms/kg) significantly enhanced the release of adrena...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00519.x
更新日期:1992-09-01 00:00:00
abstract::1. The present study examined the effects of an aqueous extract of Anoectochilus formosanus (AFE) on both hepatic fibrosis and regeneration in rats. 2. Fibrosis was induced by intraperitoneal injection of dimethylnitrosamine (DMN) for 3 consecutive days per week for 4 weeks. 3. In DMN-treated rats, liver cirrhosis-ass...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2004.04062.x
更新日期:2004-09-01 00:00:00
abstract::Clinical studies showed that high doses of recombinant human erythropoietin (rHuEPO) used to correct anaemia in chronic kidney disease (CKD) hyporesponsive patients may lead to deleterious effects. The aim of this study was to analyze the effects of rHuEPO in doses usually used to correct CKD-anaemia (100, 200 IU/kg b...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12541
更新日期:2016-03-01 00:00:00
abstract::1. Neuropeptide Y (NPY) is colocalized with catecholamines in central regions involved in blood pressure regulation and exerts depressor responses in the nucleus tractus solitarius (NTS). Ageing is accompanied by a decline in baroreflex function and a reduction in NPY concentrations in some brain areas. The present st...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb01801.x
更新日期:1997-02-01 00:00:00
abstract::1. The present report documents evidence suggesting that endothelin (ET) is a mediator and modulator of post-ganglionic sympathetic neuronal development. 2. Endothelin is produced by post-ganglionic neurons and by cells adjacent to these neurons. 3. Post-ganglionic sympathetic neurons express functional receptors for ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.1999.03179.x
更新日期:1999-12-01 00:00:00
abstract:: NADPH oxidases (Nox) are reactive oxygen species (ROS)-generating enzymes that play important physiological roles in host defence and redox signalling. However, Nox activity is upregulated in the vascular wall during atherosclerosis and contributes to plaque formation by promoting oxidative stress and inflammation. ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05657.x
更新日期:2012-03-01 00:00:00
abstract::1. Aqueous celery extract was administered intraperitoneally to genetically hypercholesterolaemic (RICO) and normocholesterolaemic (RAIF) rats via Alzet osmotic pumps over a 13 day period. 2. The serum cholesterol concentration of the celery extract-treated RICO rats was found to be significantly lower (P < 0.05) than...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb02598.x
更新日期:1996-03-01 00:00:00
abstract::1. Salt intake is not only known to play an important role in determining blood pressure (BP) but has been shown to have other deleterious effects independent of BP. 2. Epidemiological and animal studies have provided evidence that salt intake may have an adverse effect on stroke mortality independent of BP. 3. Signif...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb01976.x
更新日期:1995-03-01 00:00:00
abstract::C1q/TNF-related protein 6 (CTRP6) is a member of the CTRP family that has been reported to exhibit a nephroprotective effect. However, the role of CTRP6 in renal ischaemia/reperfusion (I/R) injury (IRI) remains unclear. In the present study, we aimed to explore the protective effect of CTRP6 in renal IRI and the poten...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13274
更新日期:2020-06-01 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::1. Heterogeneity in the receptors for the neuropeptide calcitonin gene-related peptide (CGRP) has been apparent for nearly 20 years. This is most clearly manifested in the observation of CGRP(8-37)-sensitive and -insensitive populations of CGRP-activated receptors. The pA(2) values for CGRP(8-37) in excess of 7 are wi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2007.04703.x
更新日期:2007-10-01 00:00:00
abstract::1. Synthetic human endothelin was injected intravenously over the range 1.5-50 micrograms to examine its cardiovascular actions in conscious sheep. 2. Mean arterial pressure increased by 9-21 mmHg within 30-120 s over the range 5-50 micrograms endothelin. The increase in blood pressure was associated with increased ca...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01549.x
更新日期:1989-04-01 00:00:00
abstract::1. Renin is highly expressed in submandibular gland (SMG) of mouse, which has two genes, Ren-1d and Ren-2d, but not at all in rat SMG. Differences in nuclear protein binding to renin promoter DNA were, therefore, explored. 2. Rat -169 to +23 renin DNA formed complexes with both mouse and rat extract, whereas a corresp...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01684.x
更新日期:1993-05-01 00:00:00
abstract::1. We have reported previously that instant coffee contains ligands for opiate receptors with characteristics similar to those of opiate antagonists. 2. A concentrate of receptor-active ligands from instant coffee was prepared by serial treatments involving Amberlite XAD-2, flash chromatography and gel permeation chro...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1987.tb01869.x
更新日期:1987-10-01 00:00:00
abstract::1. The leucocyte-mediated inflammatory response plays a pivotal role in ischaemia-reperfusion injury. P-Selectin and CD11b are important mediators for the recruitment of leucocytes into the endothelium. However, the time-course of changes in P-selectin and CD11b expression during reperfusion is not defined. Magnesium ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04697.x
更新日期:2007-12-01 00:00:00
abstract::1. Endogenous polyamines play a key role in mediating cellular growth and differentiation. Hypertension is associated with structural modifications of the circulatory system, a process that may be facilitated by polyamines. In this study, we examined whether there are elevated polyamine concentrations in the cardiovas...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb02750.x
更新日期:1996-05-01 00:00:00
abstract::1. Total fluid and saline intakes were greater in spontaneously hypertensive rats (SHR) than in normotensive rats (NTR). 2. Total fluid and saline intake were significantly elevated in prehypertensive SHR, 5 weeks old, compared with age-matched NTR, and the intakes fell with age in both strains but remained considerab...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1983.tb00172.x
更新日期:1983-01-01 00:00:00
abstract::1. The aim of the present study was to investigate the mechanism underlying biochanin A-induced relaxation of the aorta in spontaneously hypertensive rats (SHR). 2. The tension in isolated ring preparations of thoracic aortas from normotensive (Wistar-Kyoto (WKY) rats) and SHR at 5 and 10 weeks of age was measured iso...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04443.x
更新日期:2006-09-01 00:00:00
abstract::Age-related endothelial dysfunction is closely associated with the local production of reactive oxygen species (ROS) within and in the vicinity of the vascular endothelium. Oxidant-induced DNA damage can activate the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1), leading to endothelial dysfunction in various p...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12484
更新日期:2015-12-01 00:00:00
abstract::The aim of this study was to investigate whether enoxaparin (ENX) administration would increase seroma risk and worsen mesh tissue recovery in an experimental rat hernia repair model. Fifty-six adult male Wistar-Albino rats were included in the study. Rats were equally and randomly separated into seven groups: Group 1...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12582
更新日期:2016-07-01 00:00:00
abstract::1. Telomeres (ends of chromosomes) undergo constant remodelling during cell development, proliferation and differentiation, as well as in neoplastic cell immortalization and transformation. How the cellular microenvironment influences telomere remodelling (lengthening or shortening) remains largely unknown. 2. Recentl...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2009.05251.x
更新日期:2010-01-01 00:00:00
abstract::1. The aim of the present study was to evaluate the clinical value of colour Doppler application in encircling constriction of the superficial femoral vein in deep vein insufficiency. 2. A total of 87 patients with primary deep venous insufficiency (PDVI) using ascending venography were randomly divided into group A (...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1440-1681.2011.05620.x
更新日期:2011-12-01 00:00:00
abstract::Vancomycin is an antibiotic used in the treatment of infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus. In the last decades, vancomycin has been widely used in hospital environments due to the increasing incidence of sepsis and septic shock. Sepsis ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.13066
更新日期:2019-04-01 00:00:00
abstract::1. To facilitate investigation of diverse rodent behaviours in rodents' home cages, we have developed an integrated modular platform, the SmartCage(™) system (AfaSci, Inc. Burlingame, CA, USA), which enables automated neurobehavioural phenotypic analysis and in vivo drug screening in a relatively higher-throughput and...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2012.05719.x
更新日期:2012-07-01 00:00:00
abstract::1. The present study was undertaken to investigate the effects of aerobic physical exercise on membrane function in mild essential hypertension. 2. Hypertensive patients were divided into an exercise group (n = 8) and a non-exercise (control) group (n = 8). Physical exercise within the intensity of the anaerobic thres...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03846.x
更新日期:2003-05-01 00:00:00
abstract::Cannabinoid inverse agonists possess antidepressant-like properties, but the mechanism of this action is unknown. Numerous studies have reported the interaction between opioid and cannabinoid pathways. In this study, acute foot-shock stress was used in mice to investigate the involvement of the opioid pathway in the a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12518
更新日期:2016-02-01 00:00:00
abstract::We evaluated the role of deferasirox therapeutic drug monitoring in order to avoid toxicity or treatment failure. Plasma concentrations, measured between two consecutive liver iron determinations, were determined at the end of dosing interval. Fifty-four β-thalassemic adult patients were enrolled: 50% were males; medi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 信件
doi:10.1111/1440-1681.12879
更新日期:2018-02-01 00:00:00
abstract::1. We set out to investigate whether the administration of naloxone alone, naloxone plus vasopressin (AVP) or naloxone plus alprazolam to patients with Cushing's syndrome would result in a blunted dynamic response of the pituitary-adrenal axis compared with normal volunteers. Cushing's syndrome is often difficult to d...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1440-1681.1996.tb02785.x
更新日期:1996-06-01 00:00:00
abstract::1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb02694.x
更新日期:1997-11-01 00:00:00
abstract::1. Patients were grouped into categories of 'no airways disease', 'obstructive airways disease without response to bronchodilator' and 'obstructive airways disease with bronchodilator responsiveness'. 2. Cyclic nucleotides were assayed in specimens of lung tissue that were excised during surgery. 3. Reduced levels of ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1979.tb00013.x
更新日期:1979-01-01 00:00:00