Abstract:
:Renal cell carcinoma (RCC) is the most common kidney malignancy and has a poor prognosis owing to its resistance to chemotherapy. RCC cells overexpress the transcription factor, PAX2, normally expressed in fetal kidney but downregulated at birth. Since Pax2 suppresses apoptosis during renal development, we reasoned that PAX2 may confer resistance to cisplatin-induced apoptosis in RCC. Here, we show that PAX2 confers resistance to cisplatin-induced apoptosis in normal kidney cells and fetal kidney explants. Human embryonic kidney 293 cells transfected with a PAX2 expression vector and exposed to cisplatin (40 microM) exhibited 45 +/- 15% as much caspase-3 cleavage compared to control cells. Conversely, murine collecting duct cells stably transfected with PAX2 antisense cDNA had twofold increase in cisplatin-induced apoptosis. Murine fetal (embryonic day 15) kidney explants from PAX2(1Neu)+/- mice exposed to cisplatin (25 microM x 24 h) had 50% increased apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining). We then show that RCC cells (CAKI-1 (human, Caucasian, kidney, carcinoma) and ACHN (human, Caucasian, kidney, adenocarcinoma)) express PAX2 protein. PAX2-small interfering RNA (100 nM) reduces endogenous PAX2 protein (10% of baseline) and induces apoptosis (Annexin-V staining). Pax2 knockdown sensitized RCC cells to cisplatin-induced apoptosis, killing 50-60% of cisplatin-resistant ACHN and CAKI-1 cells. These findings suggest that PAX2 confers resistance to cisplatin-induced apoptosis in non-transformed kidney cells and fetal kidney explants. Similarly, Pax2 overexpression in RCC cells contributes to cisplatin resistance. Conceivably, a therapeutic strategy that inactivates Pax2 in vivo might enhance the efficacy of conventional cytotoxic drugs against RCC.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Hueber PA,Waters P,Clark P,Eccles M,Goodyer Pdoi
10.1038/sj.ki.5000136subject
Has Abstractpub_date
2006-04-01 00:00:00pages
1139-45issue
7eissn
0085-2538issn
1523-1755pii
S0085-2538(15)51630-Xjournal_volume
69pub_type
杂志文章abstract::An effective therapeutic means to remove relatively large polypeptide uremic toxins seems to be a hemofiltration (HF) or hemodiafiltration (HDF) employing a larger-pore membrane, that is, a protein-permeable membrane. With either method, however, a significant amount of albumin will be lost into the ultrafiltrate or d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.333
更新日期:1996-08-01 00:00:00
abstract::Defects in the primary cilium/basal body complex of renal tubular cells cause polycystic kidney disease (PKD). To uncover pathways associated with disease progression, we determined the kidney transcriptome of 10-day-old severely and mildly affected cpk mice, a model of recessive PKD. In the severe phenotype, the most...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002627
更新日期:2008-01-01 00:00:00
abstract::It has been convincingly documented that reactive oxygen species released from activated neutrophils mediate glomerular damage in experimental glomerulonephritis. Recent findings that antineutrophil cytoplasmic autoantibodies (ANCA) induce neutrophils to degranulate and produce oxygen radicals in vitro led us to explo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.233
更新日期:1993-07-01 00:00:00
abstract::Augmentation of the CD36 pathway, which involves the uptake of several endogenous ligands including free fatty acids and oxidized low-density lipoprotein, contributes to the damage of proximal tubules and podocytes, whereas ablation of CD36 attenuates renal injury. Souza et al. demonstrate that 5A peptide can inhibit ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.01.009
更新日期:2016-04-01 00:00:00
abstract::Atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have traditionally been considered separate entities. Defects in the regulation of the complement alternative pathway occur in atypical hemolytic uremic syndrome, and defects in the cleavage of von Willebrand factor (VWF)-multimers arise in thr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.03.023
更新日期:2016-07-01 00:00:00
abstract::The interaction of 15-hydroxyeicosatetraenoic acid (15-HETE) and cultured MDCK renal tubular epithelial cells was investigated to determine whether incorporation of this lipoxygenase product will affect polyphosphoinositide formation. MDCK cells were incubated with 1 microM [3H]-15-HETE for 15 to 120 minutes. Maximum ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.131
更新日期:1994-04-01 00:00:00
abstract::Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent microvascular permeability-enhancing mediator as well as a selective mitogen for vascular endothelium. In this study, in situ hybridization and immunohistochemistry co-localized VPF mRNA and protein to glomerular v...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.441
更新日期:1992-12-01 00:00:00
abstract:BACKGROUND:The clinical use of cyclosporine (CsA) is limited by its nephrotoxicity. Apoptosis, perhaps instigated by increased nitric oxide synthase (NOS) activity, may play a role in such toxicity. METHODS:Human mesangial cells, human tubular cells, human umbilical vein endothelial cells, or murine endothelial cells ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00999.x
更新日期:2000-04-01 00:00:00
abstract::Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease. The Global aHUS Registry collects real-world data on the natural history of the disease. Here we characterize end-stage renal disease (ESRD)-free survival, the rate of thrombotic microangiopathy, organ involvement and the genetic b...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2018.02.029
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:We developed an electroporation-mediated gene transfer method targeting glomerular mesangial cells. Injecting DNA solution via renal artery followed by electric pulses using tweezers-type electrodes could result in efficient transfection in mesangial cells. Therefore, this gene transfer system opened a feasi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00777.x
更新日期:2004-08-01 00:00:00
abstract::Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown. Using a two-step (1 and 5 mU x kg(-1) x min(-1)) euglycemic hyperinsulinemic clamp combined with indirect calorimetry, we ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.167
更新日期:1997-04-01 00:00:00
abstract::The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.88
更新日期:1977-08-01 00:00:00
abstract::Iron is critical for cellular, organismal, and possibly universal existence. Use of iron complexes to treat human diseases is ancient and is described in detail in Ayurveda/Siddha systems of medicine. Old aphorisms from Siddha medicine ("Alavukku Minjinal Amirdhamum Nanjagum," an elixir turns poisonous when taken in e...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.02.035
更新日期:2016-07-01 00:00:00
abstract::Unilateral ureteral obstruction results in marked changes in renal function throughout the nephron, including impaired acid and potassium secretion and salt wastage. The nephron site believed responsible for the acidification defect is the collecting duct. It has been presumed, although not demonstrated, that the cell...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.11
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:Macrophage (Mphi) infiltration may contribute to chronic renal injury. We therefore sought to examine the expression of genes associated with Mphi recruitment in the rat remnant kidney model. METHODS:Male Munich Wistar rats underwent 5/6 nephrectomy or sham operation (SHM, N = 18) and received no treatment ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00327.x
更新日期:2000-10-01 00:00:00
abstract::The biological action of calcitriol is mediated through a hormone-receptor complex interacting with nuclear chromatin. Interaction of the calcitriol receptor (VDR) with VDR response elements produces bioactive proteins which carry out the physiological actions of calcitriol. Since biological response to calcitriol app...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.252
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND:The interaction between tubular epithelial cells and calcium oxalate crystals or oxalate ions is a very precarious event in the lithogenesis. Urine contains ions, glycoproteins and glycosaminoglycans that inhibit the crystallization process and may protect the kidney against lithogenesis. We examined the eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00577.x
更新日期:2005-10-01 00:00:00
abstract::The Institute of Medicine's recent report, Organ Donation: Opportunities for Action, studies the current problems facing organ donation in the USA, making suggestions for quality improvement and analyzing various proposals of incentivized donation and presumed consent (PC). Although the report deals with the donation ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002143
更新日期:2007-04-01 00:00:00
abstract::Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that also have pleiotropic actions. They have been report...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000300
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Hypercholesterolemia may affect both endothelial function and arterial distensibility (DC). Renal transplant recipients (NTX) exhibit advanced structural and functional alterations of arterial vessel walls. The aim of this double-blind, randomized trial was to evaluate the effects of fluvastatin (FLU) on bra...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.0590041473.x
更新日期:2001-04-01 00:00:00
abstract::We have previously shown that the activity of the Na-HCO3 cotransporter is stimulated by protein kinase C (PKC) activation, but the mechanism responsible for this effect is not clear. We have shown that cultured proximal tubule cells of the rabbit have DIDS-sensitive Na-HCO3 cotransporter activity as assessed by HCO3-...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.98
更新日期:1996-03-01 00:00:00
abstract::Higher diet-dependent nonvolatile acid load is associated with faster chronic kidney disease (CKD) progression, but most studies have used estimated acid load or measured only components of the gold standard, net acid excretion (NAE). Here we measured NAE as the sum of urine ammonium and titratable acidity in 24-hour ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.09.012
更新日期:2017-01-01 00:00:00
abstract::This study was done to investigate the mechanisms that underly the changes of renal renin gene expression upon hypoperfusion of one kidney. To this end the left renal arteries of male Sprague-Dawley rats were clipped with 0.2 mm silver clips and renal renin mRNA levels were assayed by RNase protection during the first...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.440
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND:The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjec...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2000.00224.x
更新日期:2000-08-01 00:00:00
abstract::Acute elevations in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentrations are known to increase ionic chloride permeability in diverse tissues. To determine if chronic endogenous increases in cAMP are associated with sustained alterations in membrane ionic permeabilities, renal cortical brush border...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.290
更新日期:1992-08-01 00:00:00
abstract::Dual renin-angiotensin aldosterone (RAAS) blockade is associated with higher risk of hyperkalemia and has not been shown, in any outcome trial of validated renal end points, that is, doubling of creatinine, time to dialysis, or death, to be superior over other approaches. It shows promise in advanced proteinuric nephr...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2010.226
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:Arteriovenous (AV) fistulas used for hemodialysis access may affect cardiac load by increasing the preload while decreasing the afterload. In dogs, AV fistulas have also been shown to affect coronary perfusion negatively. We investigated the net effect of AV fistulas on cardiac oxygen supply and demand. MET...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00433.x
更新日期:1999-05-01 00:00:00
abstract::The selective vasopressin V2-receptor antagonist tolvaptan is eliminated almost exclusively by non-renal mechanisms. As renal impairment can influence the pharmacokinetics of drugs even when eliminated by non-renal mechanisms, we evaluated the effect of renal insufficiency on the pharmacokinetics/pharmacodynamics of t...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.2013.350
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Glucocorticoids (GC) represent the mainstay of treatment of idiopathic nephrotic syndrome (INS) and might be involved in the pathogenesis of the disease. We evaluated basal secretion of cortisol, number and affinity of glucocorticoid receptors, dexamethasone (Dex)-mediated inhibition of concanavalin-A (Con-A...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00392.x
更新日期:2004-02-01 00:00:00
abstract::We sought to study glomerular pathophysiology in a model of IgA nephropathy (IgAN). Preliminary experiments with oral immunization indicated that Lewis rats had higher IgA levels and IgA/IgG ratios than Wistar, Fischer or Sprague-Dawley rats. Six groups of Lewis rats were studied: four continuously orally immunized fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.268
更新日期:1992-07-01 00:00:00