WorldWideScience

Sample records for renal mdck cells

  1. Effect of methoxychlor on Ca(2+) movement and viability in MDCK renal tubular cells.

    Science.gov (United States)

    Cheng, He-Hsiung; Lu, Yi-Chau; Lu, Ti; Cheng, Jin-Shiung; Mar, Guang-Yuan; Fang, Yi-Chien; Chai, Kuo-Liang; Jan, Chung-Ren

    2012-10-01

    The effect of the insecticide methoxychlor on the physiology of renal tubular cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca(2+) concentrations ([Ca(2+) ](i) ) in MDCK renal tubular cells using the Ca(2+) -sensitive fluorescent dye fura-2. Methoxychlor at 5-20 μM increased [Ca(2+) ](i) in a concentration-dependent manner. The signal was reduced by 80% by removing extracellular Ca(2+) . Methoxychlor-induced Ca(2+) entry was not affected by nifedipine and SK&F96365 but was inhibited by econazole and protein kinase C modulators. In Ca(2+) -free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) partly inhibited methoxychlor-induced [Ca(2+) ](i) rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca(2+) ](i) rise. Inhibition of phospholipase C with U73122 nearly abolished methoxychlor-induced [Ca(2+) ](i) rise. At 5-15 μM, methoxychlor slightly increased cell viability, whereas at 20 μM, it decreased viability. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that 10 μM methoxychlor inhibited apoptosis, while 20 μM methoxychlor enhanced apoptosis. Methoxychlor (10 and 20 μM) increased the production of reactive oxygen species. Together, in renal tubular cells, methoxychlor induced [Ca(2+) ](i) rise by inducing phospholipase C-dependent Ca(2+) release from multiple stores and Ca(2+) entry via protein kinase C- and econazole-sensitive channels. Methoxychlor slightly enhanced or inhibited cell viability in a concentration-dependent, Ca(2+) -independent manner. Methoxychlor induced cell death that may involve apoptosis via mitochondrial pathways.

  2. Activated extracellular signal-regulated kinases are necessary and sufficient to initiate tubulogenesis in renal tubular MDCK strain I cell cysts.

    Science.gov (United States)

    Hellman, Nathan E; Greco, Andres J; Rogers, Katherine K; Kanchagar, Chitra; Balkovetz, Daniel F; Lipschutz, Joshua H

    2005-10-01

    A classic in vitro model of renal cyst and tubule formation utilizes the Madin-Darby canine kidney (MDCK) cell line, of which two strains exist. Most cyst and tubule formation studies that utilized MDCK cells have been performed with MDCK strain II cells. MDCK strain II cells form hollow cysts in a three-dimensional collagen matrix over 10 days and tubulate in response to hepatocyte growth factor, which increases levels of active (phosphorylated) ERK1/2. In this study, we demonstrate that MDCK strain I cells also form cysts when grown in a collagen matrix; however, MDCK strain I cell cysts spontaneously initiate the primary steps in tubulogenesis. Analysis of time-lapse microscopy of both MDCK strain I and strain II cell cysts during the initial stages of tubulogenesis demonstrates a highly dynamic process with cellular extensions and retractions occurring rapidly and continuously. MDCK strain I cell cysts can spontaneously initiate tubulogenesis mainly because of relatively higher levels of active ERK in MDCK strain I, compared with strain II, cells. The presence of either of two distinct inhibitors of ERK activation (UO126 and PD09059) prevents tubulogenesis from occurring spontaneously in MDCK strain I cell cysts and, in response to hepatocyte growth factor, in strain II cell cysts. The difference between MDCK strain I and strain II cell lines is likely explained by differing embryological origins, with strain I cells being of collecting duct, and hence ureteric bud, origin. Ureteric bud cells also have high levels of active ERK and spontaneously tubulate in our in vitro collagen gel system, with tubulogenesis inhibited by UO126 and PD09059. These results suggest that a seminal event in kidney development may be the activation of ERK in the mesonephric duct/ureteric bud cells destined to form the collecting tubules.

  3. Snail modulates cell metabolism in MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Haraguchi, Misako, E-mail: haraguci@m3.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Indo, Hiroko P. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Iwasaki, Yasumasa [Health Care Center, Kochi University, Kochi 780-8520 (Japan); Iwashita, Yoichiro [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Fukushige, Tomoko [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Majima, Hideyuki J. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Izumo, Kimiko; Horiuchi, Masahisa [Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Kanekura, Takuro [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Furukawa, Tatsuhiko [Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Ozawa, Masayuki [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan)

    2013-03-22

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of

  4. Renal-protective and ameliorating impacts of omega-3 fatty acids against aspartame damaged MDCK cells.

    Science.gov (United States)

    Pandurangan, Muthuraman; Enkhtaivan, Gansukh; Veerappan, Muthuviveganandavel; Mistry, Bhupendra; Patel, Rahul; Moon, So Hyun; Nagajyothi, Patnamsetty Chidanandha; Kim, Doo Hwan

    2017-09-07

    Aspartame is widely used artificial sweeteners as food additives. Several researchers have pointed that the controversial report on the use of aspartame over more than decades. Omega-3 fatty acids are essential and unsaturated fatty acids, and it plays a remarkable role in vision, intelligence, neural development, and metabolism of neurotransmitters. Therefore, the present study was aimed to investigate the effect of omega-3 fatty acids on aspartame treated renal cells. Experimental groups were divided into three such as sham control, aspartame treated, and aspartame with omega-3 fatty acids. Cell viability was determined by sulforhodamine-b assay and flow cytometric analysis. The experimental results showed that the aspartame induced altered cell viability were reduced following treatment of aspartame with omega-3 fatty acids. Altered cell morphology was recovered by omega-3 fatty acids. DNA damage appeared in the highest concentration of aspartame used in this study. DNA damage characteristics such as comet tail and tiny head sections did not appear in the omega-3 fatty acids treated cells. Several microvilli and vesicular structures were found in aspartame treated cells. Altered morphology such as rounding, microvilli, and formation of dome-like structures did not appear in the omega-3 fatty acids with aspartame treated cells. Caspase-3 mRNA and protein expression were increased in aspartame treated cells, and these levels were reduced following omega-3 fatty acids treatment. Taking all these data together, it is suggested that the omega-3 fatty acids may be a therapeutic agent to reduce the aspartame induced biochemical and morphological alterations in normal renal cells. © 2017 BioFactors, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  5. Maitotoxin activates a nonselective cation channel and stimulates Ca2+ entry in MDCK renal epithelial cells.

    Science.gov (United States)

    Dietl, P; Völkl, H

    1994-02-01

    We examined the mechanisms of maitotoxin (MTX), a water-soluble polyether from the marine dinoflagellate Gambierdiscus toxicus, in stimulation of Ca2+ entry into Mardin-Darby canine kidney cells. In the presence of bath Ca2+, MTX (3 nM) caused an elevation of the intracellular calcium concentration ([Ca2+]i), which was partially inhibited by SK&F 96365 (25 microM) or La3+ (100 microM). A stimulation of Ca(2+)-dependent K+ channels in cell-attached membrane patches coincided with this rise in [Ca2+]i and was also partially inhibited by SK&F 96365. Before the rise in [Ca2+]i, a nonselective cation current (Ins), studied by the whole-cell patch-clamp technique, was irreversibly activated. Ins poorly discriminated between Na+, K+, and Cs+, was unaffected by replacement of Cl- with gluconate-, and was not voltage gated. MTX-induced Ins was partially blocked by La3+ ions (100 microM) but not by SK&F 96365 (25 microM) or nifedipine (10 microM). SK&F 96365 by itself induced a small but significant stimulation of Ins and a rise in [Ca2+]i. The activation of Ins by MTX was instantaneous and depended on the presence of extracellular Ca2+ ions. In the absence of other cations, the inward current of Ins was dependent on the bath Ca2+ concentration. Cell-attached and excised single-channel measurements revealed that MTX activated a SK&F 96365-insensitive, approximately 40-pS, nonselective cation channel from the outside. We conclude that the initial action of MTX is the stimulation of a nonselective cation channel, which requires the presence of extracellular Ca2+ ions. The subsequent rise in [Ca2+]i is at least in part caused by another, SK&F 96365-sensitive, Ca2+ entry pathway, which may be activated as a result of or independently of Ins.

  6. Gene expression alterations during HGF-induced dedifferentiation of a renal tubular epithelial cell line (MDCK) using a novel canine DNA microarray.

    Science.gov (United States)

    Balkovetz, Daniel F; Gerrard, Edward R; Li, Shixiong; Johnson, David; Lee, James; Tobias, John W; Rogers, Katherine K; Snyder, Richard W; Lipschutz, Joshua H

    2004-04-01

    Hepatocyte growth factor (HGF) elicits a broad spectrum of biological activities, including epithelial cell dedifferentiation. One of the most widely used and best-studied polarized epithelial cell lines is the Madin-Darby canine kidney (MDCK) cell line. Here, we describe and validate the early response of polarized monolayers of MDCK cells stimulated with recombinant HGF using a novel canine DNA microarray designed to query 12,473 gene sequences. In our survey, eight genes previously implicated in the HGF signaling pathway were differentially regulated, demonstrating that the system was responsive to HGF. Also identified were 117 genes not previously known to be involved in the HGF pathway. The results were confirmed by real-time PCR or Western blot analysis for 38 genes. Of particular interest were the large number of differentially regulated genes encoding small GTPases, proteins involved in endoplasmic reticulum translation, proteins involved in the cytoskeleton, the extracellular matrix, and the hematopoietic and prostaglandin systems.

  7. Alterations of proteins in MDCK cells during acute potassium deficiency.

    Science.gov (United States)

    Peerapen, Paleerath; Ausakunpipat, Nardtaya; Chanchaem, Prangwalai; Thongboonkerd, Visith

    2016-06-01

    Chronic K(+) deficiency can cause hypokalemic nephropathy associated with metabolic alkalosis, polyuria, tubular dilatation, and tubulointerstitial injury. However, effects of acute K(+) deficiency on the kidney remained unclear. This study aimed to explore such effects by evaluating changes in levels of proteins in renal tubular cells during acute K(+) deficiency. MDCK cells were cultivated in normal K(+) (NK) (K(+)=5.3 mM), low K(+) (LK) (K(+)=2.5 mM), or K(+) depleted (KD) (K(+)=0 mM) medium for 24 h and then harvested. Cellular proteins were resolved by two-dimensional gel electrophoresis (2-DE) and visualized by SYPRO Ruby staining (5 gels per group). Spot matching and quantitative intensity analysis revealed a total 48 protein spots that had significantly differential levels among the three groups. Among these, 46 and 30 protein spots had differential levels in KD group compared to NK and LK groups, respectively. Comparison between LK and NK groups revealed only 10 protein spots that were differentially expressed. All of these differentially expressed proteins were successfully identified by Q-TOF MS and/or MS/MS analyses. The altered levels of heat shock protein 90 (HSP90), ezrin, lamin A/C, tubulin, chaperonin-containing TCP1 (CCT1), and calpain 1 were confirmed by Western blot analysis. Global protein network analysis showed three main functional networks, including 1) cell growth and proliferation, 2) cell morphology, cellular assembly and organization, and 3) protein folding in which the altered proteins were involved. Further investigations on these networks may lead to better understanding of pathogenic mechanisms of low K(+)-induced renal injury.

  8. MDCK cystogenesis driven by cell stabilization within computational analogues.

    Directory of Open Access Journals (Sweden)

    Jesse A Engelberg

    2011-04-01

    Full Text Available The study of epithelial morphogenesis is fundamental to increasing our understanding of organ function and disease. Great progress has been made through study of culture systems such as Madin-Darby canine kidney (MDCK cells, but many aspects of even simple morphogenesis remain unclear. For example, are specific cell actions tightly coupled to the characteristics of the cell's environment or are they more often cell state dependent? How does the single lumen, single cell layer cyst consistently emerge from a variety of cell actions? To improve insight, we instantiated in silico analogues that used hypothesized cell behavior mechanisms to mimic MDCK cystogenesis. We tested them through in vitro experimentation and quantitative validation. We observed novel growth patterns, including a cell behavior shift that began around day five of growth. We created agent-oriented analogues that used the cellular Potts model along with an Iterative Refinement protocol. Following several refinements, we achieved a degree of validation for two separate mechanisms. Both survived falsification and achieved prespecified measures of similarity to cell culture properties. In silico components and mechanisms mapped to in vitro counterparts. In silico, the axis of cell division significantly affects lumen number without changing cell number or cyst size. Reducing the amount of in silico luminal cell death had limited effect on cystogenesis. Simulations provide an observable theory for cystogenesis based on hypothesized, cell-level operating principles.

  9. Claudin-2 knockout by TALEN-mediated gene targeting in MDCK cells: claudin-2 independently determines the leaky property of tight junctions in MDCK cells.

    Directory of Open Access Journals (Sweden)

    Shinsaku Tokuda

    Full Text Available Tight junctions (TJs regulate the movements of substances through the paracellular pathway, and claudins are major determinants of TJ permeability. Claudin-2 forms high conductive cation pores in TJs. The suppression of claudin-2 expression by RNA interference in Madin-Darby canine kidney (MDCK II cells (a low-resistance strain of MDCK cells was shown to induce a three-fold increase in transepithelial electrical resistance (TER, which, however, was still lower than in high-resistance strains of MDCK cells. Because RNA interference-mediated knockdown is not complete and only reduces gene function, we considered the possibility that the remaining claudin-2 expression in the knockdown study caused the lower TER in claudin-2 knockdown cells. Therefore, we investigated the effects of claudin-2 knockout in MDCK II cells by establishing claudin-2 knockout clones using transcription activator-like effector nucleases (TALENs, a recently developed genome editing method for gene knockout. Surprisingly, claudin-2 knockout increased TER by more than 50-fold in MDCK II cells, and TER values in these cells (3000-4000 Ω·cm2 were comparable to those in the high-resistance strains of MDCK cells. Claudin-2 re-expression restored the TER of claudin-2 knockout cells dependent upon claudin-2 protein levels. In addition, we investigated the localization of claudin-1, -2, -3, -4, and -7 at TJs between control MDCK cells and their respective knockout cells using their TALENs. Claudin-2 and -7 were less efficiently localized at TJs between control and their knockout cells. Our results indicate that claudin-2 independently determines the 'leaky' property of TJs in MDCK II cells and suggest the importance of knockout analysis in cultured cells.

  10. Stable knockdown of Kif5b in MDCK cells leads to epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ju, E-mail: juzi.cui@gmail.com [The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing (China); Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Jin, Guoxiang; Yu, Bin [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Wang, Zai [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (China); Lin, Raozhou [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen (China)

    2015-07-17

    Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. Kif5b is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of Kif5b in epithelial cells, we examined the phenotypes of Kif5b-deficient MDCK cells. Stable knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells, and their expression levels were decreased in Kif5b-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in Kif5b depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of Kif5b in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression. - Highlights: • Knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate. • Kif5b deficient MDCK cells underwent epithelial–mesenchymal transition. • E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells. • Decreased E-cadherin and NMMIIA levels mediate EMT in Kif5b deficient MDCK cells. • Overexpression of E-cadherin and NMMIIA reverse the effects of Kif5b knockdown.

  11. Sulfur X-Ray Absorption Spectroscopy of Living Mammalian Cells: An Enabling Tool for Sulfur Metabolomics. in Situ Observation of Uptake of Taurine Into MDCK Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gnida, M.; Sneeden, E.Yu; Whitin, J.C.; Prince, R.C.; Pickering, I.J.; Korbas, M.; George, G.N.

    2009-06-01

    Sulfur is essential for life, with important roles in biological structure and function. However, because of a lack of suitable biophysical techniques, in situ information about sulfur biochemistry is generally difficult to obtain. Here, we present an in situ sulfur X-ray absorption spectroscopy (S-XAS) study of living cell cultures of the mammalian renal epithelial MDCK cell line. A great deal of information is retrieved from a characteristic sulfonate feature in the X-ray absorption spectrum of the cell cultures, which can be related to the amino acid taurine. We followed the time and dose dependence of uptake of taurine into MDCK cell monolayers. The corresponding uptake curves showed a typical saturation behavior with considerable levels of taurine accumulation inside the cells (as much as 40% of total cellular sulfur). We also investigated the polarity of uptake of taurine into MDCK cells, and our results confirmed that uptake in situ is predominantly a function of the basolateral cell surface.

  12. The carcinogen safrole increases intracellular free Ca2+ levels and causes death in MDCK cells.

    Science.gov (United States)

    Chen, Wei-Chuan; Cheng, He-Hsiung; Huang, Chun-Jen; Lu, Yih-Chau; Chen, I-Shu; Liu, Shiuh-Inn; Hsu, Shu-Shong; Chang, Hong-Tai; Huang, Jong-Khing; Chen, Jin-Shyr; Jan, Chung-Ren

    2007-02-28

    The effect of the carcinogen safrole on intracellular Ca2+ movement in renal tubular cells has not been explored previously. The present study examined whether safrole could alter Ca2+ handling in Madin-Darby canine kidney (MDCK) cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at concentrations above 33 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 400 microM. The Ca2+ signal was reduced by 90% by removing extracellular Ca2+, but was not affected by nifedipine, verapamil, or diltiazem. Addition of Ca2+ after safrole had depleted intracellular Ca(2+)-induced dramatic Ca2+ influx, suggesting that safrole caused store-operated Ca2+ entry. In Ca(2+)-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to release more Ca 2+. Inhibition of phospholipase C with 2 microM U73122 did not affect safrole-induced Ca2+ release. Trypan blue exclusion assays revealed that incubation with 650 microM safrole for 30 min did not kill cells, but killed 70% of cells after incubation for 60 min. Collectively, the data suggest that in MDCK cells, safrole induced a [Ca2+] increase by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C-independent fashion, and by inducing Ca2+ influx via store-operated Ca2+ entry. Furthermore, safrole can cause acute toxicity to MDCK cells.

  13. The exocyst localizes to the primary cilium in MDCK cells.

    Science.gov (United States)

    Rogers, Katherine K; Wilson, Patricia D; Snyder, Richard W; Zhang, Xiaoyu; Guo, Wei; Burrow, Christopher R; Lipschutz, Joshua H

    2004-06-18

    Primary cilia play a role in the maintenance of tubular epithelial differentiation and ciliary dysfunction can result in abnormal cyst formation, such as occurs in autosomal dominant polycystic kidney disease (ADPKD). We previously showed that the exocyst, an eight-protein complex involved in the biogenesis of polarity from yeast to mammals, is centrally involved in cyst formation [Mol. Biol. Cell. 11 (2000) 4259]. Here we show that the exocyst complex localizes to the primary cilium in Madin-Darby canine kidney (MDCK) tubular epithelial cells. We further show that the exocyst is overexpressed in both cell lines and primary cell cultures of ADPKD origin, suggesting that the exocyst may be involved in the pathogenesis of ADPKD.

  14. Intracellular signaling via ERK/MAPK completes the pathway for tubulogenic fibronectin in MDCK cells.

    Science.gov (United States)

    Liu, Zhao; Greco, Andres J; Hellman, Nathan E; Spector, June; Robinson, Jonathan; Tang, Oliver T; Lipschutz, Joshua H

    2007-02-16

    A classic in vitro model of branching morphogenesis utilizes the Madin-Darby canine kidney (MDCK) cell line. MDCK Strain II cells form hollow monoclonal cysts in a three-dimensional collagen matrix over the course of 10 days and tubulate in response to hepatocyte growth factor (HGF). We and our colleagues previously showed that activation of the extracellular-signal regulated kinase (ERK, aka MAPK) pathway is necessary and sufficient to induce tubulogenesis in MDCK cells. We also showed in a microarray study that one of the genes upregulated by HGF was the known tubulogene fibronectin. Given that HGF activates a multitude of signaling pathways, including ERK/MAPK, to test the intracellular regulatory pathway, we used two distinct inhibitors of ERK activation (U0126 and PD098059). Following induction of MDCK Type II cells with HGF, tubulogenic fibronectin mRNA was upregulated fourfold by real-time PCR, and minimal or no change in fibronectin expression was seen when HGF was added with either U0126 or PD098059. We confirmed these results using an MDCK cell line inducible for Raf, which is upstream of ERK. Following activation of Raf, fibronectin mRNA and protein expression were increased to a similar degree as was seen following HGF induction. Furthermore, MDCK Strain I cells, which originate from collecting ducts and have constitutively active ERK, spontaneously initiate tubulogenesis. We show here that MDCK Strain I cells have high levels of fibronectin mRNA and protein compared to MDCK Strain II cells. When U0126 and PD098059 were added to MDCK Strain I cells, fibronectin mRNA, and protein levels were decreased to levels seen in MDCK Strain II cells. These data allow us to complete what we believe is the first description of a tubulogenic pathway from receptor/ligand (HGF/CMET), through an intracellular signaling pathway (ERK/MAPK), to transcription and, finally, secretion of a critical tubuloprotein (fibronectin).

  15. Shear-induced Volume Decrease in MDCK Cells

    Science.gov (United States)

    Heo, Jinseok; Sachs, Frederick; Wang, Jianbin; Hua, Susan Z.

    2013-01-01

    Using a microfluidic cell volume sensor we measured the change in the cell volume of Madin-Darby Canine Kidney (MDCK) cells induced by shear stress. An increase in shear stress from 0.2 to 2.0 dyn/cm2 resulted in a volume decrease to a steady state volume ~ 20 – 30 % smaller than the initial resting cell volume. Independent experiments based on fluorescence quenching confirmed the volume reduction. This shear-induced cell shrinkage was irreversible on the time scale of the experiment (~ 30 min). Treatment of 0.1 μM Hg2+ significantly inhibited the volume decrease, suggesting that the shear-induced cell shrinkage is associated with water efflux through aquaporins. The volume decrease cannot be inhibited by 75 mM TEA, 100 μM DIDS, or 100 μM Gd3+ suggesting that volume reduction is not directly mediated by K+ and Cl− channels that typically function during regulatory volume decrease (RVD), nor is it through cationic stretch-activated ion channels (SACs). The process also appears to be Ca2+ independent because it was insensitive to intracellular Ca2+ level. Since cell volume is determined by the intracellular water content, we postulate that the shear induced reductions in cell volume may arise from increased intracellular hydrostatic pressure as the cell is deformed under flow, which promotes the efflux of water. The increase in internal pressure in a deformable object under the flow is supported by the finite element mechanical model. PMID:22759987

  16. Influence of NaCl, urea, potassium and pH on HSP72 expression in MDCK cells.

    Science.gov (United States)

    Neuhofer, W; Müller, E; Grünbein, R; Thurau, K; Beck, F X

    1999-12-01

    The renal inner medulla is characterised by elevated extracellular concentrations of NaCl, urea, potassium and hydrogen ions, an environment that may affect cell viability negatively. High amounts of HSP72, a stress protein allowing cells to resist harmful situations, are also observed in this region. The present study examined HSP72 induction by various medullary stress factors, individually or in combination, in MDCK cells, a renal epithelial cell line expressing characteristics of the medullary collecting duct. MDCK cells were incubated for 3 days in media containing elevated concentrations of NaCl, urea, potassium and hydrogen ions individually or in combination. HSP72 mRNA and protein expression were determined by Northern and Western blot analyses, respectively. HSP72 expression was enhanced moderately by addition of 50 mM NaCl to normal medium at pH 7.4 but enhanced strongly when added at pH 6.5. The latter degree of HSP72 induction was comparable to that observed when 150 mM NaCl was added at pH 7.4. In normal medium (pH 7.4) containing 300 mM urea, MDCK HSP72 expression was not different from controls. In contrast, urea-induced HSP72 expression was clearly evident when medium pH was lowered to 6.5. Potassium at 20 or 40 mM induced HSP72 only slightly. These results indicate that expression of HSP72 in renal epithelial cells is regulated synergistically by NaCl, urea and pH. Since HSP72 is only slightly induced by increased potassium, this probably reflects the changes in medium osmolality rather than a specific effect of potassium. The high medullary HSP72 content observed even in diuresis may be due to co-operative effects of medullary solutes on HSP72 expression.

  17. Mechanisms of RON-mediated epithelial-mesenchymal transition in MDCK cells through the MAPK pathway

    Directory of Open Access Journals (Sweden)

    Xu Xiangming

    2011-07-01

    Full Text Available The epithelial-mesenchymal transition (EMT is involved in neoplastic metastasis, and the RON protein may be involved. In the present study, we determined the role and the mechanisms of action of RON in EMT in Madin-Darby canine kidney (MDCK cells by Western blot and cell migration analysis. Activation of RON by macrophage stimulating protein (MSP results in cell migration and initiates changes in the morphology of RON-cDNA-transfected MDCK cells. The absence of E-cadherin, the presence of vimentin and an increase in Snail were observed in RE7 cells, which were derived from MDCK cells transfected with wt-RON, compared with MDCK cells. Stimulation of RE7 cells with MSP resulted in increased migration (about 69% of the wounded areas were covered as well as increased activation of extracellular signal-regulated kinase 1/2 (Erk1/2 and glycogen synthase kinase-3β (GSK-3β; the percent of the activation ratio was 143.6/599.8% and 512.4%, respectively, which could be inhibited with an individual chemical inhibitor PD98059 (50 μM specific to MAPK/ERK kinase (the percent inhibition was 98.9 and 81.2%, respectively. Thus, the results indicated that RON protein could mediate EMT in MDCK cells via the Erk1/2 pathway. Furthermore, GSK-3β regulates the function of Snail in controlling EMT by this pathway.

  18. Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells.

    Science.gov (United States)

    Robben, Joris H; Fenton, Robert A; Vargas, Sarah L; Schweer, Horst; Peti-Peterdi, Janos; Deen, Peter M T; Milligan, Graeme

    2009-12-01

    When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function.

  19. Isolation of influenza viruses in MDCK 33016PF cells and clearance of contaminating respiratory viruses.

    Science.gov (United States)

    Roth, Bernhard; Mohr, Hannah; Enders, Martin; Garten, Wolfgang; Gregersen, Jens-Peter

    2012-01-11

    This paper summarizes results obtained by multiplex PCR screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in MDCK 33016PF cells. Using the ResPlexII v2.0 (Qiagen) multiplex PCR, 393 positive results were obtained in 468 clinical samples collected during an influenza season in Germany. The overall distribution of positive results was influenza A 42.0%, influenza B 38.7%, adenovirus 1.5%, bocavirus 0.5%, coronavirus 3.3%, enterovirus 5.6%, metapneumovirus 1.0%, parainfluenza virus 0.8%, rhinovirus 4.1%, and respiratory syncytial virus (RSV) 2.5%. Double infections of influenza virus together with another virus were found for adenovirus B and E, bocavirus, coronavirus, enterovirus and for rhinovirus. These other viruses were rapidly lost upon passages in MDCK 33016PF cells and under conditions as applied to influenza virus passaging. Clinical samples, in which no influenza virus but other viruses were found, were also subject to passages in MDCK 33016PF cells. Using lower inoculum dilutions than those normally applied for preparations containing influenza virus (total dilution of the original sample of ∼10(4)), the positive results for the different viruses turned negative already after 2 or 3 passages in MDCK 33016PF cells. These results demonstrate that, under practical conditions as applied to grow influenza viruses, contaminating viruses can be effectively removed by passages in MDCK cells. In combination with their superior isolation efficiency, MDCK cells appear highly suitable to be used as an alternative to embryonated eggs to isolate and propagate influenza vaccine candidate viruses.

  20. Protective essential oil attenuates influenza virus infection: An in vitro study in MDCK cells

    Directory of Open Access Journals (Sweden)

    Metcalf Jordan P

    2010-11-01

    Full Text Available Abstract Background Influenza is a significant cause of morbidity and mortality. The recent pandemic of a novel H1N1 influenza virus has stressed the importance of the search for effective treatments for this disease. Essential oils from aromatic plants have been used for a wide variety of applications, such as personal hygiene, therapeutic massage and even medical practice. In this paper, we investigate the potential role of an essential oil in antiviral activity. Methods We studied a commercial essential oil blend, On Guard™, and evaluated its ability in modulating influenza virus, A/PR8/34 (PR8, infection in Madin-Darby canine kidney (MDCK cells. Influenza virus was first incubated with the essential oil and infectivity in MDCK cells was quantified by fluorescent focus assay (FFA. In order to determine the mechanism of effects of essential oil in viral infection inhibition, we measured hemagglutination (HA activity, binding and internalization of untreated and oil-treated virus in MDCK cells by flow cytometry and immunofluorescence microscopy. In addition, the effect of oil treatment on viral transcription and translation were assayed by relative end-point RT-PCR and western blot analysis. Results Influenza virus infectivity was suppressed by essential oil treatment in a dose-dependent manner; the number of nascent viral particles released from MDCK cells was reduced by 90% and by 40% when virus was treated with 1:4,000 and 1:6,000 dilutions of the oil, respectively. Oil treatment of the virus also decreased direct infection of the cells as the number of infected MDCK cells decreased by 90% and 45% when virus was treated with 1:2,000 and 1:3,000 dilutions of the oil, respectively. This was not due to a decrease in HA activity, as HA was preserved despite oil treatment. In addition, oil treatment did not affect virus binding or internalization in MDCK cells. These effects did not appear to be due to cytotoxicity of the oil as MDCK cell

  1. Betal-integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca2+ signalling

    DEFF Research Database (Denmark)

    Prætorius, Helle; Prætorius, Jeppe; Nielsen, Søren

    2004-01-01

    of proximal tubules and thick ascending limbs. Immunogold-electron microscopy confirmed the presence of β1-integrin on primary cilia of MDCK cells and rat collecting ducts. Intracellular Ca2+ levels, monitored by fluorescence microscopy on fluo 4-loaded MDCK cells, significantly increased on addition...

  2. Electrochemical impedance spectroscopic measurements of FCCP-induced change in membrane permeability of MDCK cells.

    Science.gov (United States)

    Zhao, Lingzhi; Li, Xianchan; Lin, Yuqing; Yang, Lifen; Yu, Ping; Mao, Lanqun

    2012-05-07

    This study demonstrates a new electrochemical impedance spectroscopic (EIS) method for measurements of the changes in membrane permeability during the process of cell anoxia. Madin-Darby canine kidney (MDCK) cells were employed as the model cells and were cultured onto gelatin-modified glassy carbon (GC) electrodes. EIS measurements were conducted at the MDCK/gelatin-modified GC electrodes with Fe(CN)(6)(3-/4-) as the redox probe. The anoxia of the cells grown onto electrode surface was induced by the addition of carbonycyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) into the cell culture, in which the MDCK/gelatin-modified GC electrodes were immersed for different times. The EIS results show that the presence of FCCP in the cell culture clearly decreases the charge-transfer resistance of the Fe(CN)(6)(3-/4-) redox probe at the MDCK/gelatin-modified GC electrodes, and the charge-transfer resistance decreases with increasing time employed for immersing the MDCK/gelatin-modified GC electrodes into the cell culture containing FCCP. These results demonstrate that the EIS method could be used to monitor the changes in the cell membrane permeability during the FCCP-induced cell anoxia. To simulate the EIS system, a rational equivalent circuit was proposed and the values of ohmic resistance of the electrolyte, charge-transfer resistance and constant phase elements for both the gelatin and the cell layers are given with the fitting error in an acceptable value. This study actually offers a new and simple approach to measuring the dynamic process of cell death induced by anoxia through monitoring the changes in the cell membrane permeability.

  3. Receptor ganglioside content of three hosts for Sendai virus. MDBK, HeLa, and MDCK cells.

    Science.gov (United States)

    Markwell, M A; Fredman, P; Svennerholm, L

    1984-08-01

    Specific gangliosides GD1a, GT1b and GQ1b isolated from brain have been shown to function as receptors for Sendai virus by conferring susceptibility to infection when they are incorporated into receptor-deficient cells (Markwell, M.A.K., Svennerholm, L. and Paulson, J.C. (1981) Proc. Natl. Acad. Sci. USA 78, 5406-5410). The endogenous gangliosides of three commonly used hosts for Sendai virus: MDBK, HeLa, and MDCK cells were analyzed to determine the amount and type of receptor gangliosides present. In all three cell lines, GM3 was the major ganglioside component. The presence of GM1, GD1a and the more complex homologs of the gangliotetraose series was also established. In cell lines derived from normal tissue, MDBK and MDCK cells, gangliosides contributed 47-65% of the total sialic acid. In HeLa cells, gangliosides contributed substantially less (17% of the total sialic acid). The ganglioside content of each cell line was shown not to be immutable but instead to depend on the state of differentiation, passage number, and surface the cells were grown on. Thus, the ganglioside concentration of undifferentiated MDCK cells was found to be substantially greater than that of MDBK or HeLa cells, but decreased as the MDCK cells underwent differentiation. Changes in culture conditions that were shown to decrease the receptor ganglioside content of the cells resulted in a corresponding decrease in susceptibility to infection. The endogenous oligosialogangliosides present in susceptible host cells were shown to function as receptors for Sendai virus.

  4. Experimental Researches on Carcinogenesis or Tumorigenicity of MDCK Canine Kidney Cell(CKC) Lines and Analysis of Their Chromosome Karyotypes

    Institute of Scientific and Technical Information of China (English)

    ZHANG De-li; FANG Fu-de; LI Liu-jin; XIA Geng-tian; HE Xu-yu; GAO Bu-xian; BAI Xiao-hong; HUANG Gao-sheng; LIU Shang-gao; YAN Long-fei

    2002-01-01

    The chromosomal number variations & structural aberrations of the MDCK cell line, primary feline or canine kidney cell(FKC or CKC) and Hela cell line were investigated and their karyotypes of conventional chromosome bands were analyzed. The carcinogenesis or tumorigenicity testing of these cell lines in about 232 nude mice and for colony formation in soft agarose and for haemagglutination under different concentration of plant lectins of these cells were carried out. Under the prerequisite that the incidence of cancer or tumor in negative-control nude mice inoculated subcutaneously with primary feline or canine kidney cell cultures purified in vitro at passage 3 was 0 (0/22) and 0 (0/10), respectively. The incidence of the progressively-growing malignant tumor(MT) in positive-control nude mice inoculated subcutaneously with Hela cell cultures of KB, X, or NM20/X strain was 10/10, 25/25 and 5/51, respectively. The results showed that the incidence of tumor in nude mice with tetrapioid YA strain of MDCK cell during 20 - 45 passages, with hypodiploid JB strain of MDCK cell on passage 25, with di-and hypoploid JC strain of MDCK cell during 2 - 15passages or with hypoploid M strain of MDCK cell during 9 - 27 passages was 28/58, 1/5, 4/18 and 0/31,respectively. The chromosomal analysis results showed that the ratio of difference in the rate of modal chromosome number between high (mcs + n) and lowest (mcs)passages was not more than 5 % - 15 % and the structure aberrations was generally 0 - 3%. These results proved that the genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species-specific. MDCK line has tumorigenicity no matter what its chromosome karyotype is, at least it has very low tumorigenicity even when its modal chromosome number is hypoploid. The repeatedly frozen, thawed and split controls of tumorigenicity-positive cell lines(X strain of Hela, M strain of BHK-21, JA strain of Vero, YA strain of MDCK) have

  5. Disruption of MDCK cell tight junctions by the free-living amoeba Naegleria fowleri.

    Science.gov (United States)

    Shibayama, Mineko; Martínez-Castillo, Moisés; Silva-Olivares, Angélica; Galindo-Gómez, Silvia; Navarro-García, Fernando; Escobar-Herrera, Jaime; Sabanero, Myrna; Tsutsumi, Víctor; Serrano-Luna, Jesús

    2013-02-01

    Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis. This parasite invades its host by penetrating the olfactory mucosa. However, the mechanism of epithelium penetration is not well understood. In the present study, we evaluated the effect of N. fowleri trophozoites and the non-pathogenic Naegleria gruberi on Madin-Darby canine kidney (MDCK) tight junction proteins, including claudin-1, occludin and ZO-1, as well as on the actin cytoskeleton. Trophozoites from each of the free-living amoeba species were co-cultured with MDCK cells in a 1 : 1 ratio for 1, 3, 6 or 10 h. Light microscopy revealed that N. fowleri caused morphological changes as early as 3 h post-infection in an epithelial MDCK monolayer. Confocal microscopy analysis revealed that after 10 h of co-culture, N. fowleri trophozoites induced epithelial cell damage, which was characterized by changes in the actin apical ring and disruption of the ZO-1 and claudin-1 proteins but not occludin. Western blot assays revealed gradual degradation of ZO-1 and claudin-1 as early as 3 h post-infection. Likewise, there was a drop in transepithelial electrical resistance that resulted in increased epithelial permeability and facilitated the invasion of N. fowleri trophozoites by a paracellular route. In contrast, N. gruberi did not induce alterations in MDCK cells even at 10 h post-infection. Based on these results, we suggest that N. fowleri trophozoites disrupt epithelial monolayers, which could enable their penetration of the olfactory epithelium and subsequent invasion of the central nervous system.

  6. Influvac: a safe Madin Darby Canine Kidney (MDCK) cell culture-based influenza vaccine.

    Science.gov (United States)

    Brands, R; Visser, J; Medema, J; Palache, A M; van Scharrenburg, G J

    1999-01-01

    Influenza vaccine production technology based on large scale cell culture technology has been developed. From the characterization of the continuous cell line MDCK as well as drug safety studies we conclude that this cell line and the cell culture system are suitable for biological production. The Down Stream Process (DSP) of the virus-containing harvest fluids guarantees sufficient inactivation of influenza viruses and adequate removal or inactivation of putative adventitious or endogenous viruses, mycoplasma or bacteria. Our data indicate that the tissue culture-based production technology is feasible.

  7. High yield production of influenza virus in Madin Darby canine kidney (MDCK cells with stable knockdown of IRF7.

    Directory of Open Access Journals (Sweden)

    Itsuki Hamamoto

    Full Text Available Influenza is a serious public health problem that causes a contagious respiratory disease. Vaccination is the most effective strategy to reduce transmission and prevent influenza. In recent years, cell-based vaccines have been developed with continuous cell lines such as Madin-Darby canine kidney (MDCK and Vero. However, wild-type influenza and egg-based vaccine seed viruses will not grow efficiently in these cell lines. Therefore, improvement of virus growth is strongly required for development of vaccine seed viruses and cell-based influenza vaccine production. The aim of our research is to develop novel MDCK cells supporting highly efficient propagation of influenza virus in order to expand the capacity of vaccine production. In this study, we screened a human siRNA library that involves 78 target molecules relating to three major type I interferon (IFN pathways to identify genes that when knocked down by siRNA lead to enhanced production of influenza virus A/Puerto Rico/8/1934 in A549 cells. The siRNAs targeting 23 candidate genes were selected to undergo a second screening pass in MDCK cells. We examined the effects of knockdown of target genes on the viral production using newly designed siRNAs based on sequence analyses. Knockdown of the expression of a canine gene corresponding to human IRF7 by siRNA increased the efficiency of viral production in MDCK cells through an unknown process that includes the mechanisms other than inhibition of IFN-α/β induction. Furthermore, the viral yield greatly increased in MDCK cells stably transduced with the lentiviral vector for expression of short hairpin RNA against IRF7 compared with that in control MDCK cells. Therefore, we propose that modified MDCK cells with lower expression level of IRF7 could be useful not only for increasing the capacity of vaccine production but also facilitating the process of seed virus isolation from clinical specimens for manufacturing of vaccines.

  8. The large GTPase Mx1 is involved in apical transport in MDCK cells.

    Science.gov (United States)

    Hoff, Florian; Greb, Christoph; Hollmann, Christina; Hönig, Ellena; Jacob, Ralf

    2014-09-01

    In epithelial cells apical proteins are transported by specific transport carriers to the correct membrane domain. The composition of these carriers is heterogeneous and comprises components such as motor proteins, annexins, lectins, Rab GTPases and cargo molecules. Here, we provide biochemical and fluorescence microscopic data to show that the dynamin-related large GTPase Mx1 is a component of post-Golgi vesicles carrying the neurotrophin receptor p75(NTR) . Moreover, siRNA-mediated depletion of Mx1 significantly decreased the transport efficiency of apical proteins in MDCK cells. In conclusion, Mx1 plays a crucial role in the delivery of cargo molecules to the apical membrane of epithelial cells.

  9. αV-integrins are required for mechanotransduction in MDCK epithelial cells.

    Directory of Open Access Journals (Sweden)

    Terhi P Teräväinen

    Full Text Available The properties of epithelial cells within tissues are regulated by their immediate microenvironment, which consists of neighboring cells and the extracellular matrix (ECM. Integrin heterodimers orchestrate dynamic assembly and disassembly of cell-ECM connections and thereby convey biochemical and mechanical information from the ECM into cells. However, the specific contributions and functional hierarchy between different integrin heterodimers in the regulation of focal adhesion dynamics in epithelial cells are incompletely understood. Here, we have studied the functions of RGD-binding αV-integrins in a Madin Darby Canine Kidney (MDCK cell model and found that αV-integrins regulate the maturation of focal adhesions (FAs and cell spreading. αV-integrin-deficient MDCK cells bound collagen I (Col I substrate via α2β1-integrins but failed to efficiently recruit FA components such as talin, focal adhesion kinase (FAK, vinculin and integrin-linked kinase (ILK. The apparent inability to mature α2β1-integrin-mediated FAs and link them to cellular actin cytoskeleton led to disrupted mechanotransduction in αV-integrin deficient cells seeded onto Col I substrate.

  10. αV-integrins are required for mechanotransduction in MDCK epithelial cells.

    Science.gov (United States)

    Teräväinen, Terhi P; Myllymäki, Satu M; Friedrichs, Jens; Strohmeyer, Nico; Moyano, Jose V; Wu, Chuanyue; Matlin, Karl S; Muller, Daniel J; Manninen, Aki

    2013-01-01

    The properties of epithelial cells within tissues are regulated by their immediate microenvironment, which consists of neighboring cells and the extracellular matrix (ECM). Integrin heterodimers orchestrate dynamic assembly and disassembly of cell-ECM connections and thereby convey biochemical and mechanical information from the ECM into cells. However, the specific contributions and functional hierarchy between different integrin heterodimers in the regulation of focal adhesion dynamics in epithelial cells are incompletely understood. Here, we have studied the functions of RGD-binding αV-integrins in a Madin Darby Canine Kidney (MDCK) cell model and found that αV-integrins regulate the maturation of focal adhesions (FAs) and cell spreading. αV-integrin-deficient MDCK cells bound collagen I (Col I) substrate via α2β1-integrins but failed to efficiently recruit FA components such as talin, focal adhesion kinase (FAK), vinculin and integrin-linked kinase (ILK). The apparent inability to mature α2β1-integrin-mediated FAs and link them to cellular actin cytoskeleton led to disrupted mechanotransduction in αV-integrin deficient cells seeded onto Col I substrate.

  11. Trafficking of the IKs -Complex in MDCK Cells

    DEFF Research Database (Denmark)

    David, Jens-Peter; Andersen, Martin N; Olesen, Søren-Peter

    2013-01-01

    has not been unequivocally resolved yet. We employed trafficking-deficient K 7.1 and KCNE1 mutants to investigate I trafficking using the polarized Madin-Darby Canine Kidney cell line. We find that the assembly happens early in the secretory pathway but provide three lines of evidence that it takes......The voltage-gated potassium channel K 7.1 is regulated by non-pore forming regulatory KCNE ß-subunits. Together with KCNE1, it forms the slowly activating delayed rectifier potassium current I . However, where the subunits assemble and which of the subunits determines localization of the I -complex...

  12. Transepithelial transport of aliphatic carboxylic acids studied in Madin Darby canine kidney (MDCK) cell monolayers.

    Science.gov (United States)

    Cho, M J; Adson, A; Kezdy, F J

    1990-04-01

    Transport of 14C-labeled acetic, propionic (PA), butyric, valeric, heptanoic (HA), and octanoic (OA) acids across the Madin Darby canine kidney (MDCK) epithelial cell monolayer grown on a porous polycarbonate membrane was studied in Hanks' balanced salt solution (HBSS) at 37 degrees C in both apical-to-basolateral and basolateral-to-apical directions. At micromolar concentrations of solutes, metabolic decomposition was significant as evidenced by [14C]CO2 production during the OA transport. The apparent permeability (Pe) indicates that as lipophilicity increases, diffusion across the "unstirred" boundary layer becomes rate limiting. In support of this notion, transport of OA and HA was enhanced by agitation, showed an activation energy of 3.7 kcal/mol for OA, and resulted in identical Pe values for both transport directions. Analysis of Pe changes with varying alkyl chain length resulted in a delta G of -0.68 +/- 0.09 kcal/mol for -CH2-group transfer from an aqueous phase to the MDCK cells. When the intercellular tight junctions were opened by the divalent chelator EGTA in Ca2+/Mg2(+)-free HBSS, transport of the fluid-phase marker Lucifer yellow greatly increased because of paracellular leakage. PA transport also showed a significant increase, but OA transport was independent of EGTA. Although albumin also undergoes paracellular transport in the presence of EGTA and OA binds strongly to albumin, OA transport in EGTA solution was unchanged by albumin. These observations indicate that transmembrane transport is the major mechanism for lipophilic substances. The present study, together with earlier work on the transport of polar substances, shows that the MDCK cell monolayer is an excellent model of the transepithelial transport barrier.

  13. Forskolin stimulation promotes urea transporter UT-A1 ubiquitination, endocytosis, and degradation in MDCK cells.

    Science.gov (United States)

    Su, Hua; Carter, Conner B; Laur, Oskar; Sands, Jeff M; Chen, Guangping

    2012-11-01

    The adenylyl cyclase stimulator forskolin (FSK) stimulates UT-A1 phosphorylation, membrane trafficking, and urea transport activity. Here, we found that FSK stimulation induces UT-A1 ubiquitination in UT-A1 Madin-Darby canine kidney (MDCK) cells. This suggests that phosphorylation by FSK also triggers the protein degradation machinery for UT-A1. UT-A1-MDCK cells were treated with 100 μg/ml cycloheximide to inhibit protein synthesis, with or without 10 μM FSK. Total UT-A1 protein abundance was significantly reduced after FSK treatment, concomitantly ubiquitinated UT-A1 was increased. We then specifically investigated the effect of FSK on UT-A1 expressed on the cell plasma membrane. FSK treatment accelerated UT-A1 removal from the cell plasma membrane by increasing UT-A1 endocytosis as judged by biotinylation/MesNa treatment and confocal microscopy. We further found that inhibition of the clathrin-mediated endocytic pathway, but not the caveolin-mediated endocytic pathway, significantly blocks FSK-stimulated UT-A1 endocytosis. The PKA inhibitor H89 and the proteasome inhibitors MG132 and lactacystin reduced FSK-induced membrane UT-A1 reduction. Our study shows that FSK activates the UT-A1 urea transporter and the activation/phosphorylation subsequently triggers the downregulation of UT-A1, which represents an important mechanism for the cell to return to the basal conditions after vasopressin stimulation.

  14. Transport of lipid nano-droplets through MDCK epithelial cell monolayer.

    Science.gov (United States)

    Khatri, Pulkit; Shao, Jun

    2017-05-01

    This study aims to investigate the transport of lipid nano-droplets through MDCK epithelial cell monolayer. Nanoemulsions of self-nano-emulsifying drug delivery systems (SNEDDS) labeled with radioactive C18 triglyceride were developed. The effect of droplet size and lipid composition on the transport was investigated. The results showed that the lipid nano-droplet transport through MDCK cell monolayer was as high as 2.5%. The transport of lipid nano-droplets was higher for nanoemulsions of medium chain glycerides than the long chain glycerides. The transport was reduced by more than half when the average lipid nano-droplet size increased from 38nm to 261nm. The droplet size measurement verified the existence of lipid nano-droplets in the receiver chamber only when the nanoemulsions were added to the donor chamber but not when the surfactant or saline solution was added. Cryo-TEM images confirmed the presence of lipid nano-droplets in both donor and receiver chamber at the end of transport study. In conclusion, lipid nano-droplets can be transported through the cell monolayer. This finding may help to further explore the oral and other non-invasive delivery of macromolecules loaded inside SNEDDS.

  15. Thiamine uptake into primary proximal tubule cells and MDCK distal tubule cells; Differential effect of ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Pochal, M.A.; Taub, M.; Acara, M. (State Univ. of New York, Buffalo (United States))

    1991-03-11

    Rabbit primary proximal tubule cells (PT) and distal cells from a MDCK cell line (DT) were studied for their ability to accumulate and metabolize {sup 14}C-thiamine and to assess the effect of ethanol on the accumulation. Incubation with 10uM {sup 14}C-thiamine, resulted in a four fold greater accumulation of {sup 14}C in PT compared to DT. Ethanol significantly decreased PT thiamine accumulation to 0.92 {plus minus} 0.09 nmole/mg but had little effect on DT accumulation. Initial thiamine uptake rates were greater in PT than in DT. Ethanol did not produce a significant effect on either initial uptake rate. Ethanol, however, decreased the maximum rate of uptake in PR from 3.20 to 1.75 nmole/mg/min. Although both cell types metabolize {sup 14}C to thiamine phosphates, total amount of metabolite was greater in PT. These data are consistent with cortical slice uptake studies in which thiamine accumulation was associated with its phosphorylation. In these slices both maximal accumulation and metabolism were inhibited by ethanol.

  16. Infection of Polarized MDCK Cells with Herpes Simplex Virus 1: Two Asymmetrically Distributed Cell Receptors Interact with Different Viral Proteins

    Science.gov (United States)

    Sears, Amy E.; McGwire, Bradford S.; Roizman, Bernard

    1991-06-01

    Herpes simplex virus 1 attaches to at least two cell surface receptors. In polarized epithelial (Madin-Darby canine kidney; MDCK) cells one receptor is located in the apical surface and attachment to the cells requires the presence of glycoprotein C in the virus. The second receptor is located in the basal surface and does not require the presence of glycoprotein C. Exposure of MDCK cells at either the apical or basal surface to wild-type virus yields plaques and viral products whereas infection by a glycoprotein C-negative mutant yields identical results only after exposure of MDCK cells to virus at the basal surface. Multiple receptors for viral entry into cells expand the host range of the virus. The observation that glycoprotein C-negative mutants are infectious in many nonpolarized cell lines suggests that cells in culture may express more than one receptor and explains why genes that specify the viral proteins that recognize redundant receptors, like glycoprotein C, are expendable.

  17. Further Report on Carcinogenesis or Tumorigenicity of MDCK Canine Kidney Cell(CKC) Lines and Analysis of Their Chromosome Karyotypes

    Institute of Scientific and Technical Information of China (English)

    ZHANG De-li; FANG Fu-de; XIA Geng-tian; HE Xu-yu; GAO Bu-xian; BAI Xiao-hong; LI Liu-jin; HUANG Gao-sheng; LIU Shang-gao; YEN Lung-fei

    2002-01-01

    Using Hela cell cultures as positive control and primary canine kidney cell (CKC) or feline kidney cell (FKC) cultures purified in vitro on passage 3 as negative control, the tumorigenicity of Madin-Darby canine kidney (MDCK) cells was tested in >273 nude mice, and colony formation in soft agarose and haemagglutination under different concentration of plant lectins of these cells were carried out at the same time. Subsequently, very low tumorigenicity strains of MDCK line were successfully selected; these were evaluated for the production of canine or feline combination viral vaccines, free of infectious agents, and of known cytogenetic and tumorigenic. It is thus evident that MDCK cell of M, JB, JC, WB or H strain can be approved as substrate for the preparation of attenuated viral vaccines, but MDCK cell of YA, YB and KA strains can not be approved as substrate for the preparation of attenuated viral vaccines. The heritable character of these cell sub-lines is comparatively stable, and shows little significant difference between passages.

  18. Segregated mathematical model for growth of anchorage-dependent MDCK cells in microcarrier culture.

    Science.gov (United States)

    Möhler, Lars; Bock, Andreas; Reichl, Udo

    2008-01-01

    To describe the growth behavior of anchorage-dependent mammalian cells in microcarrier systems, various approaches comprising deterministic and stochastic single cell models as well as automaton-based models have been presented in the past. The growth restriction of these often contact-inhibited cells by spatial effects is described at levels with different complexity but for the most part not taking into account their metabolic background. Compared to suspension cell lines these cells have a comparatively long lag phase required for attachment and start of proliferation on the microcarrier. After an initial phase of exponential growth only a moderate specific growth rate is achieved due to restrictions in space available for cell growth, limiting medium components, and accumulation of growth inhibitors. Here, a basic deterministic unstructured segregated cell model for growth of Madin Darby Canine Kidney (MDCK) cells used in influenza vaccine production is described. Four classes of cells are considered: cells on microcarriers, cells in suspension, dead cells, and lysed cells. Based on experimental data, cell attachment and detachment is taken explicitly into account. The model allows simulation of the overall growth behavior in microcarrier culture, including the lag phase. In addition, it describes the time course of uptake and release of key metabolites and the identification of parameters relevant for the design and optimization of vaccine manufacturing processes.

  19. Heterogeneity of the MDCK cell line and its applicability for influenza virus research.

    Directory of Open Access Journals (Sweden)

    Vladimir Y Lugovtsev

    Full Text Available Single-cell clones have been established from the MDCK cell line, characterized for their morphology and evaluated for their suitability for influenza virus research. Three discrete cell morphotypes were identified using light microscopy. Besides morphological features, the cell types can be distinguished by the level of expression of surface glycans recognized by peanut agglutinin (PNA. All clones were susceptible to infection by influenza viruses of different subtypes of influenza A virus (H1N1, H1N1pdm09, H3N2, H5N1 and influenza B virus, and all possessed on their surface terminally sialylated glycans with both types of glycosidic linkage (α2-3 and α2-6. The Type-1 cell lines were able to support a multicycle replication of influenza A and B viruses without help of an exogenous trypsin. In contrast, cell lines exhibiting Type-2 morphology were unable to support multicycle replication of influenza A viruses without trypsin supplementation. Western blot analysis of the hemagglutinin of H1N1 strains demonstrated that Type-2 cells were deficient in production of proteolytically activated hemagglutinin (no cleavage between HA1/HA2 was observed. HA1/HA2 cleavage of influenza B viruses in the Type-2 cells was also significantly impaired, but not completely abrogated, producing sufficient amount of activated HA to support efficient virus replication without trypsin. In contrast, all clones of Type-1 cells were able to produce proteolytically activated hemagglutinin of influenza A and B viruses. However, the growth kinetics and plaque size of influenza A viruses varied significantly in different clones. Influenza B virus also showed different plaque size, with the biggest plaque formation in the Type-2 cells, although the growth kinetics and peak infectivity titers were similar in all clones. Taken together, the study demonstrates that the population of original MDCK cells is represented by various types of cells that differ in their capacities to

  20. Glycolysis is governed by growth regime and simple enzyme regulation in adherent MDCK cells.

    Directory of Open Access Journals (Sweden)

    Markus Rehberg

    2014-10-01

    Full Text Available Due to its vital importance in the supply of cellular pathways with energy and precursors, glycolysis has been studied for several decades regarding its capacity and regulation. For a systems-level understanding of the Madin-Darby canine kidney (MDCK cell metabolism, we couple a segregated cell growth model published earlier with a structured model of glycolysis, which is based on relatively simple kinetics for enzymatic reactions of glycolysis, to explain the pathway dynamics under various cultivation conditions. The structured model takes into account in vitro enzyme activities, and links glycolysis with pentose phosphate pathway and glycogenesis. Using a single parameterization, metabolite pool dynamics during cell cultivation, glucose limitation and glucose pulse experiments can be consistently reproduced by considering the cultivation history of the cells. Growth phase-dependent glucose uptake together with cell-specific volume changes generate high intracellular metabolite pools and flux rates to satisfy the cellular demand during growth. Under glucose limitation, the coordinated control of glycolytic enzymes re-adjusts the glycolytic flux to prevent the depletion of glycolytic intermediates. Finally, the model's predictive power supports the design of more efficient bioprocesses.

  1. A highly calcium-selective cation current activated by intracellular calcium release in MDCK cells.

    Science.gov (United States)

    Delles, C; Haller, T; Dietl, P

    1995-08-01

    1. The whole-cell patch clamp technique and fluorescence microscopy with the Ca2+ indicators fura-2 and fluo-3 were used to measure the whole-cell current and the free intracellular Ca2+ concentration ([Ca2+]i) in Madin-Darby canine kidney (MDCK) cells. 2. In a Ca(2+)-free bath solution, thapsigargin (TG) caused a transient increase of [Ca2+]i. Subsequent addition of Ca2+ caused a long lasting elevation of [Ca2+]i. 3. In a Ca(2+)-free bath solution, extracellular application of TG, ATP or ionomycin, or intracellular application of inositol 1,4,5-trisphosphate (IP3), caused a small but significant inward current (Iin) and a transient outward Ca(2+)-dependent K+ current (IK(Ca)), consistent with intracellular Ca2+ release. Subsequent addition of Ca2+ induced a prominent Iin with a current density of -4.2 +/- 0.7 pA pF-1. This Iin was unaffected by inositol 1,3,4,5-tetrakisphosphate (IP4). 4. Na+ replacement by mannitol, N-methyl-D-glucamine+ (NMG+), aminomethylidin-trimethanol+ (Tris+) or choline+ reduced Iin by 54, 65, 52 and 56%, respectively. This indicates an apparent Ca2+ selectivity over Na+ of 26:1. Iin was, however, unaffected by replacing Cl- with gluconate- or by the K+ channel blocker charybdotoxin (CTX). 5. Iin was completely blocked by La3+ (IC50 = 0.77 microM). Consistently, La3+ completely reversed the TG-induced elevation of [Ca2+]i. SK&F 96365 (1-[3-(4-methoxyphenyl)-propoxyl]-1-(4-methoxy-phenyl)-ethyl-1H-im idazole) HCl did not inhibit the TG-induced Iin. It did, however, exhibit a biphasic effect on [Ca2+]i, consisting of an initial Ca2+ decay and a subsequent Ca2+ elevation. La3+ completely reversed the SK&F 96365-induced elevation of [Ca2+]i. 6. In the absence of Na+, Iin was dependent on the bath Ca2+ concentration (EC50 = 1.02 mM). Ca2+ replacement by Ba2+ or Mn2+ resulted in a reduction of Iin by 95 and 94%, respectively. 7. From these experiments we conclude that Ca2+ release from intracellular Ca2+ stores, induced by different independent

  2. Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Min [Department of Biological Sciences, University of Columbia, NY (United States); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Attieh, Zouhair K. [Department of Laboratory Science and Technology, American University of Science and Technology, Ashrafieh (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Son, Hee Sook [Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University (Korea, Republic of); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Chen, Huijun [Medical School, Nanjing University, Nanjing 210008, Jiangsu Province (China); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Bacouri-Haidar, Mhenia [Department of Biology, Faculty of Sciences (I), Lebanese University, Hadath (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Vulpe, Chris D., E-mail: vulpe@berkeley.edu [Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in non-polarized cells. Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in iron deficient and polarized cells. Black-Right-Pointing-Pointer Hephaestin with apical iron moves near to basolateral membrane of polarized cells. Black-Right-Pointing-Pointer Peri-basolateral location of hephaestin is accessible to the extracellular space. Black-Right-Pointing-Pointer Hephaestin is involved in iron mobilization from the intestine to circulation. -- Abstract: While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO{sub 4}) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a

  3. Factors affecting ammonium uptake by C11 clone of MDCK cells.

    Science.gov (United States)

    Tararthuch, A L; Fernandez, R; Ramirez, M A; Malnic, G

    2002-11-01

    In several tissues ammonium ions are able to use the transport pathways of other ions, particularly of K+. We investigated this possibility in the C11 clone of MDCK cells, thought to represent intercalated cells, in control and 0 Cl- conditions. Cell pH was measured by ratiometric fluorescence microscopy using the pH indicator BCECF. After preincubating the cells for 10 min in control or 0 Cl- (substituted by gluconate) Ringer, an ammonium pulse was applied to induce cell acidification. The magnitude of the initial alkalinization (DeltapH) was 0.24+/-0.03 ( n=28) pH units in controls, which fell to 0.023+/-0.01 ( n=12) in 0 Cl-, suggesting uptake of NH4+ balancing the alkalinization by NH3. Addition of 10(-3) M bumetanide or furosemide to the 0 Cl- medium, or 10(-4 )M hexamethylene amiloride, did not alter DeltapH. However, with 5 mM Ba+, DeltapH increased to 38% of control. When 2.5x10(-4) M ouabain, an inhibitor of Na+-K+ ATPase, was used, DeltapH increased to 46% of control. Inhibition of H+-K+ ATPase by SCH28080 or by omeprazol caused significant increase in DeltapH. In 0 Cl- solution, these cells underwent a mean volume reduction (-d V) of -10.24+/-1.96% per 10 min as measured by confocal microscopy. To investigate if NH4+ influx was regulated by cell volume or by cell Cl-, volume reduction was avoided by two procedures. When preincubating with NPPB, a Cl- channel blocker, in 0 Cl-, volume reduction was inhibited (d V=-2.12% per 10 min), and DeltapH was 0.24+/-0.04 ( n=5). When the cells were preincubated in hypotonic 0 Cl- (260 mosmol/l), cell volume reduction was abolished (d V=+2.6% per 10 min) and DeltapH was 0.52+/-0.07 ( n=7). Thus, activation of NH4+ influx by several transporters was due to volume reduction rather than to [Cl-] alteration.

  4. Predicting MDCK cell permeation coefficients of organic molecules using membrane-interaction QSAR analysis

    Institute of Scientific and Technical Information of China (English)

    Li-li CHEN; Jia YAO; Jian-bo YANG; Jie YANG

    2005-01-01

    Aim: To use membrane-interaction quantitative structure-activity relationship analysis (MI-QSAR) to develop predictive models of partitioning of organic compounds in gastrointestinal cells. Methods: A training set of 22 structurally diverse compounds, whose apparent permeability accross cellular membranes of MadinDarby canine kidney (MDCK) cells were measured, were used to construct MIQSAR models. Molecular dynamic simulations were used to determine the explicit interaction of each test compound (solute) with a dimyristoyl-phosphatidyl-choline monolayer membrane model. An additional set of intramolecular solute descriptors were computed and considered in the trial pool of descriptors for building MI-QSAR models. The QSAR models were optimized using multidimensional linear regression fitting and the stepwise method. A test set of 8 compounds were evaluated using the MI-QSAR models as part of a validation process. Results:MI-QSAR models of the gastrointestinal absorption process were constructed.The descriptors found in the best MI-QSAR models are as follows: 1) ClogP (the logarithm of the 1-octanol/water partition coefficient); 2) EHOMO (the highest occupied molecular orbital energy); 3) Es (stretch energy); 4) PMY (the principal moment of inertia Y, the inertia along the y axis in the rectangular coordinates; 5) Ct(total connectivity); and 6) Enb (the energy of interactions between all of the nonbonded atoms). The most important descriptor in the models is ClogP. Conclusion:Permeability is not only determined by the properties of drug molecules, but is also very much influenced by the molecule-membrane interaction process.

  5. The effect of hydrophilic and hydrophobic structure of amphiphilic polymeric micelles on their transport in epithelial MDCK cells.

    Science.gov (United States)

    Yu, Chao; He, Bing; Xiong, Meng-Hua; Zhang, Hua; Yuan, Lan; Ma, Ling; Dai, Wen-Bing; Wang, Jun; Wang, Xing-Lin; Wang, Xue-Qing; Zhang, Qiang

    2013-08-01

    The interaction of nanocarriers with cells including their transcellular behavior is vital not only for a drug delivery system, but also for the safety of nanomaterials. In an attempt to clarify how the structures of polymers impact the transport mechanisms of their nanocarriers in epithelial cells, three amphiphilic polymers (PEEP-PCL, PEG-PCL and PEG-DSPE) with different hydrophilic or hydrophobic blocks were synthesized or chosen to form different micelle systems here. The endocytosis, exocytosis, intracellular colocalization, paracellular permeability and transcytosis of these micelle systems were compared using Förster resonance energy transfer analysis, real-time confocal images, colocalization assay, transepithelial electrical resistance study, and so on. All micelle systems were found intact during the studies with cells. The endocytosis and exocytosis studies with undifferentiated MDCK cells and the transcytosis study with differentiated MDCK monolayers all indicated the fact that PEG-DSPE micelles achieved the most and fastest transport, followed by PEG-PCL and PEEP-PCL in order. These might be because DSPE has higher hydrophobicity than PCL while PEG has lower hydrophilicity than PEEP. Different in hydrophilic or hydrophobic structures, all kinds of micelles demonstrated similar pathways during endocytosis and exocytosis, both caveolae- and clathrin-mediated but with difference in degree. The colocalization studies revealed different behaviors in intracellular trafficking among the three polymer micelles, suggesting the decisive role of hydrophilic shells on this process. Finally, all micelle systems did not impact the paracellular permeability of test cell monolayer. In conclusion, the hydrophilic and hydrophobic structures of test micelles could influence their transport ability, intracellular trafficking and the transport level under each pathway in MDCK cells.

  6. Effect of human activated NRAS on replication of delNS1 H5N1 influenza virus in MDCK cells

    Directory of Open Access Journals (Sweden)

    Zou Wei

    2011-05-01

    Full Text Available Abstract Background RAS, coded by ras proto-oncogenes, played an important role in signal transmission to regulate cell growth and differentiation. Host activation of RAS was significant for IFN-sensitive vaccinia virus (delE3L or attenuate influenza virus in unallowable cells. Results Huamn NRAS gene was activated by mutating in codon 61. Then the activation of NRAS was detected by western blot in MDCK cells. The delNS1 H5N1 influenza virus with deletion of NS1 eIF4GI binding domain was weak multiplication in MDCK cells. And the replication of delNS1 virus and expression of IFN-beta and IRF-3 were detected by Real-time PCR in MDCK cells infected with delNS1 virus. It was found that the delNS1 virus had a significant increase in MDCK cells when the NRAS was activated, and yet, expression of IRF-3 and IFN-beta were restrained. Conclusions The study demonstrated that activated NRAS played an important part for delNS1 virus replication in MDCK cells. Activated NRAS might be down-regulating the expression of antiviral cellular factors in delNS1 virus infected cells.

  7. Spatio-temporal PLC activation in parallel with intracellular Ca2+ wave propagation in mechanically stimulated single MDCK cells.

    Science.gov (United States)

    Tsukamoto, Akira; Hayashida, Yasunori; Furukawa, Katsuko S; Ushida, Takashi

    2010-03-01

    Intracellular Ca2+ transients are evoked either by the opening of Ca2+ channels on the plasma membrane or by phospholipase C (PLC) activation resulting in IP3 production. Ca2+ wave propagation is known to occur in mechanically stimulated cells; however, it remains uncertain whether and how PLC activation is involved in intracellular Ca2+ wave propagation in mechanically stimulated cells. To answer these questions, it is indispensable to clarify the spatio-temporal relations between intracellular Ca2+ wave propagation and PLC activation. Thus, we visualized both cytosolic Ca2+ and PLC activation using a real-time dual-imaging system in individual Mardin-Darby Canine Kidney (MDCK) cells. This system allowed us to simultaneously observe intracellular Ca2+ wave propagation and PLC activation in a spatio-temporal manner in a single mechanically stimulated MDCK cell. The results showed that PLC was activated not only in the mechanically stimulated region but also in other subcellular regions in parallel with intracellular Ca2+ wave propagation. These results support a model in which PLC is involved in Ca2+ signaling amplification in mechanically stimulated cells.

  8. Expression Profile of Drug and Nutrient Absorption Related Genes in Madin-Darby Canine Kidney (MDCK Cells Grown under Differentiation Conditions

    Directory of Open Access Journals (Sweden)

    Balvinder S. Vig

    2012-06-01

    Full Text Available The expression levels of genes involved in drug and nutrient absorption were evaluated in the Madin-Darby Canine Kidney (MDCK in vitro drug absorption model. MDCK cells were grown on plastic surfaces (for 3 days or on Transwell® membranes (for 3, 5, 7, and 9 days. The expression profile of genes including ABC transporters, SLC transporters, and cytochrome P450 (CYP enzymes was determined using the Affymetrix® Canine GeneChip®. Expression of genes whose probe sets passed a stringent confirmation process was examined. Expression of a few transporter (MDR1, PEPT1 and PEPT2 genes in MDCK cells was confirmed by RT-PCR. The overall gene expression profile was strongly influenced by the type of support the cells were grown on. After 3 days of growth, expression of 28% of the genes was statistically different (1.5-fold cutoff, p < 0.05 between the cells grown on plastic and Transwell® membranes. When cells were differentiated on Transwell® membranes, large changes in gene expression profile were observed during the early stages, which then stabilized after 5–7 days. Only a small number of genes encoding drug absorption related SLC, ABC, and CYP were detected in MDCK cells, and most of them exhibited low hybridization signals. Results from this study provide valuable reference information on endogenous gene expression in MDCK cells that could assist in design of drug-transporter and/or drug-enzyme interaction studies, and help interpret the contributions of various transporters and metabolic enzymes in studies with MDCK cells.

  9. Cloning of the canine RNA polymerase I promoter and establishment of reverse genetics for influenza A and B in MDCK cells

    Directory of Open Access Journals (Sweden)

    Duke Gregory M

    2007-10-01

    Full Text Available Abstract Background Recent incidents where highly pathogenic influenza A H5N1 viruses have spread from avian species into humans have prompted the development of cell-based production of influenza vaccines as an alternative to or replacement of current egg-based production. Madin-Darby canine kidney (MDCK cells are the primary cell-substrate candidate for influenza virus production but an efficient system for the direct rescue of influenza virus from cloned influenza cDNAs in MDCK cells did not exist. The objective of this study was to develop a highly efficient method for direct rescue of influenza virus in MDCK cells. Results The eight-plasmid DNA transfection system for the rescue of influenza virus from cloned influenza cDNAs was adapted such that virus can be generated directly from MDCK cells. This was accomplished by cloning the canine RNA polymerase I (pol I promoter from MDCK cells and exchanging it for the human RNA pol I promoter in the eight plasmid rescue system. The adapted system retains bi-directional transcription of the viral cDNA template into both RNA pol I transcribed negative-sense viral RNA and RNA pol II transcribed positive-sense viral mRNA. The utility of this system was demonstrated by rescue in MDCK cells of 6:2 genetic reassortants composed of the six internal gene segments (PB1, PB2, PA, NP, M and NS from either the cold-adapted (ca influenza A vaccine strain (ca A/Ann Arbor/1/60 or the ca influenza B vaccine strain (ca B/Ann Arbor/1/66 and HA and NA gene segments from wild type influenza A and B strains. Representative 6:2 reassortants were generated for influenza A (H1N1, H3N2, H5N1, H6N1, H7N3 and H9N2 and for both the Victoria and Yamagata lineages of influenza B. The yield of infectious virus in the supernatant of transfected MDCK cells was 106 to 107 plaque forming units per ml by 5 to 7 days post-transfection. Conclusion This rescue system will enable efficient production of both influenza A and influenza B

  10. Monitoring changes in proteome during stepwise adaptation of a MDCK cell line from adherence to growth in suspension.

    Science.gov (United States)

    Kluge, Sabine; Benndorf, Dirk; Genzel, Yvonne; Scharfenberg, Klaus; Rapp, Erdmann; Reichl, Udo

    2015-08-20

    Adaptation of continuous cell lines to growth in suspension in a chemically defined medium has significant advantages for design and optimization in manufacturing of biologicals. In this work, changes in the protein expression level during a step-wise adaptation of an adherent Madin Darby canine kidney (MDCK) cell line to suspension growth were analyzed. Therefore, three cell line adaptations were performed independently. Two adaptations were monitored closely to characterize short term changes in protein expression levels after serum deprivation. In addition, initial stages of suspension growth were analyzed for both adaptations. The third adaptation involved MDCK suspension cells (MDCKSUS2) grown over an extended time period to achieve robust growth characteristics. Here, cells of the final stage of adaptation were compared with their parental cell line (MDCKADH). A combination of two dimensional differential gel electrophoresis for relative protein quantification and tandem mass spectrometry for protein identification enabled insights into cellular physiology. The two closely monitored cell line adaptations followed different routes regarding specific changes in protein expression but resulted in similar proteome profiles at the initial stages of suspension growth analyzed. Compared to the MDCKADH cells more than 90% of all changes in the protein expression level were identified after serum deprivation and were related to cytoskeletal structure, genetic information processing and cellular metabolism. Myosin proteins, involved in cellular detachment by actin-myosin contractile mechanisms were also differentially expressed. Interestingly, for both of the two adaptations, proteins linked for tumorigenicity, like lactoylglutathione lyase and sulfotransferase 1A1 were differentially expressed. In contrast, none of these proteins were differentially expressed for the MDCKSUS2 cell line. Overall, proteomic monitoring allowed identification of key proteins involved in

  11. The characteristics and antigenic properties of recently emerged subclade 3C.3a and 3C.2a human influenza A(H3N2) viruses passaged in MDCK cells.

    Science.gov (United States)

    Lin, Yipu; Wharton, Stephen A; Whittaker, Lynne; Dai, Mian; Ermetal, Burcu; Lo, Janice; Pontoriero, Andrea; Baumeister, Elsa; Daniels, Rodney S; McCauley, John W

    2017-05-01

    Two new subclades of influenza A(H3N2) viruses became prominent during the 2014-2015 Northern Hemisphere influenza season. The HA glycoproteins of these viruses showed sequence changes previously associated with alterations in receptor-binding properties. To address how these changes influence virus propagation, viruses were isolated and propagated in conventional MDCK cells and MDCK-SIAT1 cells, cells with enhanced expression of the human receptor for the virus, and analysed at each passage. Gene sequence analysis was undertaken as virus was passaged in conventional MDCK cells and MDCK-SIAT1 cells. Alterations in receptor recognition associated with passage of virus were examined by haemagglutination assays using red blood cells from guinea pigs, turkeys and humans. Microneutralisation assays were performed to determine how passage-acquired amino acid substitutions and polymorphisms affected virus antigenicity. Viruses were able to infect MDCK-SIAT1 cells more efficiently than conventional MDCK cells. Viruses of both the 3C.2a and 3C.3a subclades showed greater sequence change on passage in conventional MDCK cells than in MDCK-SIAT1 cells, with amino acid substitutions being seen in both HA and NA glycoproteins. However, virus passage in MDCK-SIAT1 cells at low inoculum dilutions showed reducing infectivity on continued passage. Current H3N2 viruses should be cultured in the MDCK-SIAT1 cell line to maintain faithful replication of the virus, and at an appropriate multiplicity of infection to retain infectivity. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  12. The transcription factor LEF-1 induces an epithelial–mesenchymal transition in MDCK cells independent of β-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Wakako; Ozawa, Masayuki, E-mail: mozawa@m.kufm.kagoshima-u.ac.jp

    2013-12-06

    Highlights: •The transcription factor LEF-1 induces an EMT in MDCK cells. •A mutant LEF-1 that cannot interact with β-catenin retained the ability. •The nuclear function of β-catenin was not necessary for the LEF-1-induced EMT. •The mRNA levels of Slug, ZEB1, and ZEB2 increased significantly in these cells. -- Abstract: The epithelial–mesenchymal transition (EMT), a key process in the tumor metastatic cascade, is characterized by the loss of cell–cell junctions and cell polarity, as well as the acquisition of migratory and invasive properties. LEF-1 is a member of the lymphoid enhancer-binding factor/T-cell factor (LEF/TCF) family of DNA-binding transcription factors, which interact with nuclear β-catenin and act as central transcriptional mediators of Wnt signaling. To investigate the role of LEF-1 in EMT, we generated stable LEF-1 transfectants using MDCK cells. The transfectants had a spindle-shaped mesenchymal morphology, and enhanced migration and invasiveness relative to control cells. These EMT changes were accompanied by the downregulation of an epithelial marker protein, E-cadherin, and the upregulation of mesenchymal marker proteins, vimentin and N-cadherin. Consistent with these observations, the mRNA levels of Slug, ZEB1, and ZEB2—EMT-related transcription factors—increased significantly. Although the N-terminally deleted mutant LEF-1 cannot interact with β-catenin, it retained the ability to induce EMT. Consistent with these observations, neither the expression of a dominant negative β-catenin/engrailed chimera, nor the expression of a cytoplasmic domain of E-cadherin that sequesters β-catenin from binding to LEF/TCF, reversed LEF-1-induced EMT. Together, these data indicated that the nuclear function of β-catenin was not necessary for the induction of Slug, ZEB1, and ZEB2 expression leading to EMT.

  13. Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition*

    Science.gov (United States)

    Tauro, Bow J.; Mathias, Rommel A.; Greening, David W.; Gopal, Shashi K.; Ji, Hong; Kapp, Eugene A.; Coleman, Bradley M.; Hill, Andrew F.; Kusebauch, Ulrike; Hallows, Janice L.; Shteynberg, David; Moritz, Robert L.; Zhu, Hong-Jian; Simpson, Richard J.

    2013-01-01

    Epithelial-mesenchymal transition (EMT) is a highly conserved morphogenic process defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. EMT is associated with increased aggressiveness, invasiveness, and metastatic potential in carcinoma cells. To assess the contribution of extracellular vesicles following EMT, we conducted a proteomic analysis of exosomes released from Madin-Darby canine kidney (MDCK) cells, and MDCK cells transformed with oncogenic H-Ras (21D1 cells). Exosomes are 40–100 nm membranous vesicles originating from the inward budding of late endosomes and multivesicular bodies and are released from cells on fusion of multivesicular bodies with the plasma membrane. Exosomes from MDCK cells (MDCK-Exos) and 21D1 cells (21D1-Exos) were purified from cell culture media using density gradient centrifugation (OptiPrep™), and protein content identified by GeLC-MS/MS proteomic profiling. Both MDCK- and 21D1-Exos populations were morphologically similar by cryo-electron microscopy and contained stereotypical exosome marker proteins such as TSG101, Alix, and CD63. In this study we show that the expression levels of typical EMT hallmark proteins seen in whole cells correlate with those observed in MDCK- and 21D1-Exos, i.e. reduction of characteristic inhibitor of angiogenesis, thrombospondin-1, and epithelial markers E-cadherin, and EpCAM, with a concomitant up-regulation of mesenchymal makers such as vimentin. Further, we reveal that 21D1-Exos are enriched with several proteases (e.g. MMP-1, -14, -19, ADAM-10, and ADAMTS1), and integrins (e.g. ITGB1, ITGA3, and ITGA6) that have been recently implicated in regulating the tumor microenvironment to promote metastatic progression. A salient finding of this study was the unique presence of key transcriptional regulators (e.g. the master transcriptional regulator YBX1) and core splicing complex components (e.g. SF3B1, SF3B3, and SFRS1) in mesenchymal 21D1-Exos. Taken

  14. Alteration of Tight and Adherens Junctions on 50-Hz Magnetic Field Exposure in Madin Darby Canine Kidney (MDCK Cells

    Directory of Open Access Journals (Sweden)

    Zoltán Somosy

    2004-01-01

    Full Text Available Adherens (AJ and tight junctions (TJ, as integrated parts of the junctional complex, are multifunctional specialized regions of the cell membrane in epithelial cells. They are responsible for cell-to-cell interactions and also have great importance in cellular signaling processes including Wnt protein-mediated signals. As electromagnetic field (EMF exposure is known to cause alterations in the function as well as supramolecular organization of different cell contacts, our goal was to investigate the effect of 50-Hz magnetic field (MF exposures on the subcellular distribution of some representative structural proteins (occludin, β-catenin, and cadherin found in AJ and TJ. Additionally, cellular β-catenin content was also quantified by Western blot analysis. 50-Hz MF exposures seemed to increase the staining intensity (amount of occludin, cadherins, and β-catenin in the junctional area of MDCK cells, while Western blot data indicated the quantity of b-catenin was found significantly decreased at both time points after EM exposures. Our results demonstrate that MF are able to modify the distribution of TJ and AJ structural proteins, tending to stabilize these cell contacts. The quantitative changes of β-catenin suggest a causative relationship between MF effects on the cell junctional complex and the Wnt signaling pathway.

  15. C-Phycocyanin Confers Protection against Oxalate-Mediated Oxidative Stress and Mitochondrial Dysfunctions in MDCK Cells

    Science.gov (United States)

    Farooq, Shukkur M.; Boppana, Nithin B.; Asokan, Devarajan; Sekaran, Shamala D.; Shankar, Esaki M.; Li, Chunying; Gopal, Kaliappan; Bakar, Sazaly A.; Karthik, Harve S.; Ebrahim, Abdul S.

    2014-01-01

    Oxalate toxicity is mediated through generation of reactive oxygen species (ROS) via a process that is partly dependent on mitochondrial dysfunction. Here, we investigated whether C-phycocyanin (CP) could protect against oxidative stress-mediated intracellular damage triggered by oxalate in MDCK cells. DCFDA, a fluorescence-based probe and hexanoyl-lysine adduct (HEL), an oxidative stress marker were used to investigate the effect of CP on oxalate-induced ROS production and membrane lipid peroxidation (LPO). The role of CP against oxalate-induced oxidative stress was studied by the evaluation of mitochondrial membrane potential by JC1 fluorescein staining, quantification of ATP synthesis and stress-induced MAP kinases (JNK/SAPK and ERK1/2). Our results revealed that oxalate-induced cells show markedly increased ROS levels and HEL protein expression that were significantly decreased following pre-treatment with CP. Further, JC1 staining showed that CP pre-treatment conferred significant protection from mitochondrial membrane permeability and increased ATP production in CP-treated cells than oxalate-alone-treated cells. In addition, CP treated cells significantly decreased the expression of phosphorylated JNK/SAPK and ERK1/2 as compared to oxalate-alone-treated cells. We concluded that CP could be used as a potential free radical-scavenging therapeutic strategy against oxidative stress-associated diseases including urolithiasis. PMID:24691130

  16. Effect of Size, Shape, and Surface Modification on Cytotoxicity of Gold Nanoparticles to Human HEp-2 and Canine MDCK Cells

    Directory of Open Access Journals (Sweden)

    Yinan Zhang

    2012-01-01

    Full Text Available There have been increasing interests in applying gold nanoparticles in biological research, drug delivery, and therapy. As the interaction of gold nanoparticles with cells relies on properties of nanoparticles, the cytotoxicity is complex and still under debating. In this work, we investigate the cytotoxicity of gold nanoparticles of different encapsulations, surface charge states, sizes and shapes to both human HEp-2 and canine MDCK cells. We found that cetyltrimethylammonium-bromide- (CTAB- encapsulated gold nanorods (GNRs were relatively higher cytotoxic than GNRs undergone further polymer coating and citrate stabilized gold nanospheres (GNSs. The toxicity of CTAB-encapsulated GNRs was mainly caused by CTAB on GNRs' surface but not free CTAB in the solution. No obvious difference was found among GNRs of different aspect ratios. Time-lapse study revealed that cell death caused by GNRs occurred predominately within one hour through apoptosis, whereas cell death by free CTAB was in a time- and dose-dependent manner. Both positively and negatively surface-charged polymer-coated GNRs (PSS-GNRs and PAH-PSS-GNRs showed similar levels of cytotoxic, suggesting the significance of surface functionality rather than surface charge in this case.

  17. Establishment of Master Cell Stock and Working Cell Bank of MDCK Lines and Selection and Evaluation of the Lines as Candidate Viral Substrates for Approval Production of Combinational Canine Attenuated-live Virus Vaccines

    Institute of Scientific and Technical Information of China (English)

    ZHANG De-li; FANG Fu-de; LI Liu-jin; XIA Geng-tian; HE Xu-yu; GAO Bu-xian; BAI Xiao-hong; HUANG Gao-sheng; LIU Shang-gao; YEN Lung-fei

    2002-01-01

    Under the prerequisite that the incidence of cancer or tumor in negative-control nude mice inoculated subcutaneously with primary feline or canine kidney cell cultures purified in vitro at passage 3 was 0(0/22) and 0 (0/10), respectively. The incidence of the progressively-growing malignant tumor(MT) in positive-control nude mice inoculated subcutaneously with Hela cell cultures of KB, X, or NM20/X strain was 10/10, 25/25 and 5/51, respectively. The results showed that the incidence of tumor in nude mice with di-and hyperploid YB strain of MDCK cell during 17 - 23 passages, with hyper- and hypoploid KA strain of MDCK cell during 6 - 8 passages, with hypoploid WB strain of MDCK cell on passage 6, with hyper-and hypopioid H strain of MDCK cell during 8 - 24 passages was 2/24, 6/10, 5/10 and 10/15, respectively. The chromosomal analysis results showed that the ratio of difference in the rate of modal chromosome number between high(mcs + n) and lowest (mcs)passages was not more than 5- 15% and the structure aberrations was generally 0-3%. These results proved that the genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species-specific. MDCK line has tumorigenicity no matter what its chromosome karyotype is, at least it has very low tumorigenicity even when its modal chromosome number is hypoploid. It is thus evident that MDCK cell of WB or H strain can be approved as substrate for the preparation of attenuated viral vaccines, but MDCK cell of YB or KA strain can not be approved as substrate for the preparation of attenuated viral vaccines.

  18. ZO-1 knockout by TALEN-mediated gene targeting in MDCK cells: involvement of ZO-1 in the regulation of cytoskeleton and cell shape.

    Directory of Open Access Journals (Sweden)

    Shinsaku Tokuda

    Full Text Available ZO-1, ZO-2 and ZO-3 are tight junction-associated scaffold proteins that bind to transmembrane proteins of tight junctions and the underlying cytoskeleton. ZO-1 is involved in the regulation of cytoskeletal organization, but its detailed molecular mechanism is less well understood. Gene knockout is an ideal method to investigate the functions of proteins that might have redundant functions such as ZO proteins, when compared with methods such as RNA interference-mediated suppression of gene expression. In this study we applied transcription activator-like effector nucleases (TALENs, a recently developed genome editing method for gene knockout, and established ZO-1 knockout clones in Madin-Darby canine kidney (MDCK cells. ZO-1 knockout induced striking changes in myosin organization at cell-cell contacts and disrupted the localization of tight junction proteins; these findings were previously unseen in studies of ZO-1 knockdown by RNA interference. Rescue experiments revealed that trace ZO-1 expression reversed these changes while excessive ZO-1 expression induced an intensive zigzag shape of cell-cell junctions. These results suggest a role for ZO-1 in the regulation of cytoskeleton and shape of cell-cell junctions in MDCK cells and indicate the advantage of knockout analysis in cultured cells.

  19. Rational design of medium supplementation strategy for improved influenza viruses production based on analyzing nutritional requirements of MDCK Cells.

    Science.gov (United States)

    Huang, Ding; Xia-Hou, Kang; Liu, Xu-Ping; Zhao, Liang; Fan, Li; Ye, Zhaoyang; Tan, Wen-Song; Luo, Jian; Chen, Ze

    2014-12-12

    Influenza vaccine production using cell culture technology has become popular nowadays. However, to meet the ever increasing demand of influenza vaccine, it is prerequisite to improve the yield of influenza virus in cells. To achieve this, in the present study, the nutritional requirements of MDCK cells in the virus production process were analyzed and a nutrient-feeding strategy was developed accordingly. Based on the consumption rates and corresponding concentration optimization, glucose and fast metabolized amino acids were supplemented into the maintaining medium at the time of infection. Compared with the non-supplemented culture, the average cell specific death rate during 0-48 h post-infection was 0.013 h(-1), which was 40.91% lower in the nutrient-supplemented culture. Total virus titer, HA antigen protein concentration and cell-specific virus yield were (1.88±0.23)×10(3) HA units/50μL, 11.70±0.22 μg/mL and (10.06±1.16)×10(3) virions/cell, respectively, which were 84.04±22.50%, 31.46±2.87% and 86.64±25.81% higher than those in the control, respectively. These data showed that the appropriate supplementation of nutrients during virus production process could reduce cell death, and improve cell-specific virus yield and total influenza virus output. This study laid foundation for the development of cell culture technology for influenza vaccine production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

    OpenAIRE

    Zhi-xiang Yuan; Jingxin Mo; Guixian Zhao; Gang Shu; Hua-lin Fu; Wei Zhao

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...

  1. Research progress of MDCK cell culture-based influenza vaccine%基于MDCK细胞培养的流感疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    王石磊; 陈则

    2012-01-01

    流感一直是威胁全世界人类健康的疾病,每年引起数以亿计的人感染.疫苗是防控流感的重要手段.除了传统的鸡胚制备的流感疫苗,基于哺乳动物细胞培养的流感疫苗已研制成功.此文重点介绍Madin-Darby犬肾(Madin-Darby canine kidney,MDCK)细胞的不同培养方式,以及基于MDCK细胞培养的流感疫苗的研究进展.%Influenza is a disease which still threatens human health in the world,being responsible for hundred millions infections every year.Vaccination is an important way to prevent and control influenza.In addition to traditional chicken embryo-prepared influenza vaccine,mammalian cell culture-derived influenza vaccine has been developed successfully.This article mainly reviews different culture methods of Madin-Darby canine kidney (MDCK) cells and current research progress of MDCK cell culture-based influenza vaccine.

  2. Attenuation of influenza virus infectivity with herbal-marine compound (HESA-A: an in vitro study in MDCK cells

    Directory of Open Access Journals (Sweden)

    Mehrbod Parvaneh

    2012-02-01

    Full Text Available Abstract Background The influenza virus is still one of the most important respiratory risks affecting humans which require effective treatments. In this case, traditional medications are of interest. HESA-A is an active natural biological compound from herbal-marine origin. Previous studies have reported that the therapeutic properties of HESA-A are able to treat psoriasis vulgaris and cancers. However, no antiviral properties have been reported. Methods This study was designed to investigate the potential antiviral properties of HESA-A and its effects in modulating TNF-α and IL-6 cytokine levels. HESA-A was prepared in normal saline as a stock solution (0.8 mg/ml, pH = 7.4. Percentages of cell survival when exposed to different concentrations of HESA-A at different time intervals was determined by MTT assay. To study the potential antiviral activity of HESA-A, Madin-Darby Canine Kidney (MDCK cells were treated with the effective concentration (EC50 of HESA-A (0.025 mg/ml and 100 TCID50/0.1 ml of virus sample under different types of exposure. Results Based on the MTT method and hemagglutination assay (HA, HESA-A is capable of improving cell viability to 31% and decreasing HA titre to almost 99% in co-penetration exposures. In addition, based on quantitative real-time PCR (qRT-PCR and enzyme-linked immunosorbent assay (ELISA, it was found that HESA-A causes decrements in TNF-α and IL-6 cytokine expressions, which was significant for TNF-α (p ≤ 0.05 but not for IL-6. Conclusion In conclusion, HESA-A was effective against influenza infection through suppressing cytokine expression.

  3. Production of high-titer human influenza A virus with adherent and suspension MDCK cells cultured in a single-use hollow fiber bioreactor.

    Science.gov (United States)

    Tapia, Felipe; Vogel, Thomas; Genzel, Yvonne; Behrendt, Ilona; Hirschel, Mark; Gangemi, J David; Reichl, Udo

    2014-02-12

    Hollow fiber bioreactors (HFBRs) have been widely described as capable of supporting the production of highly concentrated monoclonal antibodies and recombinant proteins. Only recently HFBRs have been proposed as new single-use platforms for production of high-titer influenza A virus. These bioreactors contain multiple hollow fiber capillary tubes that separate the bioreactor in an intra- and an extra-capillary space. Cells are usually cultured in the extra-capillary space and can grow to a very high cell concentration. This work describes the evaluation of the single-use hollow fiber bioreactor PRIMER HF (Biovest International Inc., USA) for production of influenza A virus. The process was setup, characterized and optimized by running a total of 15 cultivations. The HFBRs were seeded with either adherent or suspension MDCK cells, and infected with influenza virus A/PR/8/34 (H1N1), and the pandemic strain A/Mexico/4108/2009 (H1N1). High HA titers and TCID₅₀ of up to 3.87 log₁₀(HA units/100 μL) and 1.8 × 10(10)virions/mL, respectively, were obtained for A/PR/8/34 influenza strain. Influenza virus was collected by performing multiple harvests of the extra-capillary space during a virus production time of up to 12 days. Cell-specific virus yields between 2,000 and 8,000 virions/cell were estimated for adherent MDCK cells, and between 11,000 and 19,000 virions/cell for suspension MDCK.SUS2 cells. These results do not only coincide with the cell-specific virus yields obtained with cultivations in stirred tank bioreactors and other high cell density systems, but also demonstrate that HFBRs are promising and competitive single-use platforms that can be considered for commercial production of influenza virus.

  4. Production of inactivated influenza H5N1 vaccines from MDCK cells in serum-free medium.

    Directory of Open Access Journals (Sweden)

    Alan Yung-Chih Hu

    Full Text Available BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK cells grown in a serum-free (SF medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6 cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA units/50 µL and 7.1 ± 0.3 × 10(8 pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production.

  5. Complete Knockout of Endogenous Mdr1 (Abcb1) in MDCK Cells by CRISPR-Cas9.

    Science.gov (United States)

    Simoff, Ivailo; Karlgren, Maria; Backlund, Maria; Lindström, Anne-Christine; Gaugaz, Fabienne Z; Matsson, Pär; Artursson, Per

    2016-02-01

    Madin-Darby canine kidney II cells transfected with one or several transport proteins are commonly used models to study drug transport. In these cells, however, endogenous transporters such as canine Mdr1/P-glycoprotein (Abcb1) complicate the interpretation of transport studies. The aim of this investigation was to establish a Madin-Darby canine kidney II cell line using CRISPR-Cas9 gene-editing technology to knock out endogenous canine Mdr1 (cMdr1) expression. CRISPR-Cas9-mediated Abcb1 homozygous disruption occurred at frequencies of around 20% and resulted in several genotypes. We selected 1 clonal cell line, cMdr1 KO Cl2, for further examination. Consistent with an on-target effect of CRISPR-Cas9 in specific regions of the endogenous canine Abcb1 gene, we obtained a cell clone with Abcb1 gene alterations and without any cMdr1 expression, as confirmed by genome sequencing and quantitative protein analysis. Functional studies of these cells, using digoxin and other prototypic MDR1 substrates, showed close to identical transport in the apical-to-basolateral and basolateral-to-apical directions, resulting in efflux ratios indistinguishable from unity.

  6. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  7. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  8. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells.

    Science.gov (United States)

    Yuan, Zhi-Xiang; Mo, Jingxin; Zhao, Guixian; Shu, Gang; Fu, Hua-Lin; Zhao, Wei

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rationale for therapies targeting this aggressive cell population. Precise identification of renal CSC populations and the complete cell hierarchy will accurately inform characterization of disease subtypes. This will ultimately contribute to more personalized and targeted therapies. Here, we summarize potential targeting strategies for renal cancer cells and renal CSCs, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTOR), interleukins, CSC marker inhibitors, bone morphogenetic protein-2, antibody drug conjugates, and nanomedicine. In conclusion, targeting therapies for RCC represent new directions for exploration and clinical investigation and they plant a seed of hope for advanced clinical care.

  9. Cyclooxygenase-2-dependent phosphorylation of the pro-apoptotic protein Bad inhibits tonicity-induced apoptosis in renal medullary cells.

    Science.gov (United States)

    Küper, Christoph; Bartels, Helmut; Beck, Franz-X; Neuhofer, Wolfgang

    2011-11-01

    During antidiuresis, cell survival in the renal medulla requires cyclooxygenase-2 (COX-2) activity. We have recently found that prostaglandin E2 (PGE2) promotes cell survival by phosphorylation and, hence, inactivation of the pro-apoptotic protein Bad during hypertonic stress in Madin-Darby canine kidney (MDCK) cells in vitro. Here we determine the role of COX-2-derived PGE(2) on phosphorylation of Bad and medullary apoptosis in vivo using COX-2-deficient mice. Both wild-type and COX-2-knockout mice constitutively expressed Bad in tubular epithelial cells of the renal medulla. Dehydration caused a robust increase in papillary COX-2 expression, PGE2 excretion, and Bad phosphorylation in wild-type, but not in the knockout mice. The abundance of cleaved caspase-3, a marker of apoptosis, was significantly higher in papillary homogenates, especially in tubular epithelial cells of the knockout mice. Knockdown of Bad in MDCK cells decreased tonicity-induced caspase-3 activation. Furthermore, the addition of PGE2 to cells with knockdown of Bad had no effect on caspase-3 activation; however, PGE2 caused phosphorylation of Bad and substantially improved cell survival in mock-transfected cells. Thus, tonicity-induced COX-2 expression and PGE2 synthesis in the renal medulla entails phosphorylation and inactivation of the pro-apoptotic protein Bad, thereby counteracting apoptosis in renal medullary epithelial cells.

  10. Renal type a intercalated cells contain albumin in organelles with aldosterone-regulated abundance.

    Directory of Open Access Journals (Sweden)

    Thomas Buus Jensen

    Full Text Available Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1, late endosomes/lysosomes (cathepsin D or recycling endosomes (Rab11. Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells.

  11. Reevaluating the Role of Acanthamoeba Proteases in Tissue Invasion: Observation of Cytopathogenic Mechanisms on MDCK Cell Monolayers and Hamster Corneal Cells

    Directory of Open Access Journals (Sweden)

    Maritza Omaña-Molina

    2013-01-01

    Full Text Available The morphological analysis of the cytopathic effect on MDCK cell monolayers and hamster cornea and qualitative and quantitative analyses of conditioned medium and proteases were evaluated and compared between two strains of Acanthamoeba genotype T4. Further than highlighting the biological differences found between both strains, the most important observation in this study was the fact that proteases both in total extracts and in conditioned medium are apparently not determinant in tissue destruction. An interestingly finding was that no lysis of corneal tissue was observed as it was previously suggested. These results, together with previous studies, allow us to conclude that the invasion and disruption of corneal tissue is performed by the penetration of the amoebae through cell junctions, either by the action of proteases promoting cellular separation but not by their destruction and/or a mechanical effect exerted by amoebae. Therefore, contact-dependent mechanisms in Acanthamoeba pathogenesis are more relevant than it has been previously considered. This is supported because the phagocytosis of recently detached cells as well as those attached to the corneal epithelium leads to the modification of the cellular architecture facilitating the migration and destruction of deeper layers of the corneal epithelium.

  12. An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells.

    Science.gov (United States)

    Vanachayangkul, P; Byer, K; Khan, S; Butterweck, V

    2010-07-01

    Teas prepared from the fruits of Ammi visnaga L. (syn. "Khella") have been traditionally used in Egypt as a remedy to treat kidney stones. It was the aim of our study to evaluate the effect of a Khella extract (KE) as well as the two major constituents khellin and visnagin on renal epithelial injury using LLC-PK1 and Madin-Darby-canine kidney (MDCK) cells. Both cell lines provide suitable model systems to study cellular processes that are possibly involved in the development of a renal stone. LLC-PK1 and MDCK cell lines were exposed to 300 microM oxalate (Ox) or 133 microg/cm(2) calcium oxalate monohydrate (COM) in presence or absence of 10, 50, 100 or 200 microg/mL KE. To evaluate cell damage, cell viability was assessed by determining the release of lactate dehydrogenase (LDH). KE (e.g. 100 microg/ml) significantly decreased LDH release from LLC-PK1 (Ox: 8.46+0.76%; Ox + 100 microg/ml KE: 5.41+0.94%, p<0.001) as well as MDCK cells (Ox: 30.9+6.58%; Ox+100 microg/ml KE: 17.5+2.50%, p<0.001), which indicated a prevention of cell damage. Similar effects for KE were observed in both cell lines when COM crystals were added. In LLC-PK1 cells khellin and visnagin both decreased the % LDH release significantly in cells that were pretreated with Ox or COM crystals. However, khellin and visnagin exhibited different responses in MDCK cells. Whereas khellin slightly reduced the % LDH release after exposure of the cells to Ox and COM crystals, visnagin significantly decreased % LDH release only after COM crystal exposure. Overall both compounds were more active in LLC-PK1 than in MDCK cells. In summary, exposure of renal epithelial cells to Ox or COM crystals was associated with a significant release of LDH indicating cell injury. Our data demonstrate that KE as well as khellin and visnagin could prevent renal epithelial cell damage caused by Ox and COM and could therefore play a potential role in the prevention of stone formation associated with hyperoxaluria.

  13. L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation

    Directory of Open Access Journals (Sweden)

    Shujue Li

    2016-08-01

    Full Text Available Background/Aims: The interactions between calcium oxalate monohydrate (COM crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. Methods: Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry. Results: Dedifferentiated MDCK cells induced by transforming growth factor β1 (TGF-β1 shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3β/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion. Conclusions: COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3β/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis.

  14. Renal tubule cell repair following acute renal injury.

    Science.gov (United States)

    Humes, H D; Lake, E W; Liu, S

    1995-01-01

    Experimental data suggests the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent upon predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair and ischemic and nephrotoxic acute renal failure, and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes. In this regard, there is a prominent vasoconstrictor response of the renal vasculature during the postischemic period of developing acute renal failure. The intravenous administration of pharmacologic doses of atrial natriuretic factor (ANF) in the postischemic period have proven efficacious by altering renal vascular resistance, so that renal blood flow and glomerular filtration rate improve. ANF also appears to protect renal tubular epithelial integrity and holds significant promise as a therapeutic agent in acute renal failure. Of equal or greater promise are the therapeutic interventions targeting the proliferative reparative zone during the postischemic period. The exogenous administration of epidermal growth factor or insulin-like growth factor-1 in the postischemic period have effectively decreased the degree of renal insufficiency as measured by the peak serum creatinine and has hastened renal recovery as measured by the duration of time required to return the baseline serum creatinine values. A similarly efficacious role for hepatocyte growth factor has also been recently demonstrated.

  15. How renal cells handle urea.

    Science.gov (United States)

    Bagnasco, S M

    2000-01-01

    The urine concentration process requires an osmolality gradient along the renal cortico-medullary axis, with highest values in the renal papilla. NaCl and urea are the major solutes in the renal inner medulla, concentrations of urea up to 500-600 mM are found in the rat renal papilla. Urea can diffuse across cell membranes and contributes to balance intracellular and extracellular osmotic equilibrium. However, urea has perturbing effects on enzyme activity, and in concentrations above 300 mM is toxic for renal cultured cells. There is increasing evidence that urea can induce cellular responses distinct from those due to NaCl and other non-permeable solutes, including upregulation of immediate-early genes (IEGs). Urea transport by epithelial and endothelial cells is important for intra-medullary urea recycling and preservation of high urea concentration in the inner medulla. Trans-cellular movement of urea in cells expressing urea transporters may influence intracellular levels of this solute and modulate urea-induced signaling pathways. Regulation of urea transporters expression and activity can therefore be viewed as one aspect of cellular adaptation to urea. We have identified tonicity-responsive transcription as one mechanism regulating expression of the urea transporter UT-A. The short-term and long-term effects of variable extracellular urea concentration on the function of renal cells remain still unclear.

  16. 犬SLAM基因真核表达载体的构建及在MDCK细胞中的稳定表达%Construction of Eukaryotic Expressing Vector of SLAM Gene and Establishment of Its Stable Expressing MDCK Cell

    Institute of Scientific and Technical Information of China (English)

    褚秀玲; 苏建青; 江成; 张吉清; 马秀亮

    2012-01-01

    To construction a MDCK cell line stably expressing signalling lymphocyte activation molecules (SLAM). The SLAM gene of cellular receptor of CDV was amplified by RT-PCR from canine peripheral blood lymphocytes. The correctly identified SLAM gene was inserted into the eukaryotic expression vector pcDNA3.1(+) to construct the recombinant plasmid pcDNA3.1/ SLAM. The pcDNA3.1/SLAM was transfected into MDCK cells by Lipofectamine. The stably expressing MDCK cell was screened with DMEM medium under the drug selection of G418. The single clone strain was purified by limiting dilution. The results indicated that the eukaryotic expression vector pcDNA3,l/SLAM was successfully constructed, then the stable expressing MDCK cell line was obtained.%为了构建稳定表达犬信号淋巴细胞激活因子(SLAM)的MDCK细胞系,该研究从犬外周血淋巴细胞中克隆了犬瘟热病毒(Canine distemper virus,CDV)细胞受体SLAM基因,将鉴定正确的SLAM基因插入到高效真核表达载体pcDNA3.1(+)中.采用脂质体转染的方式将重组质粒pcDNA3.1/SLAM转染到MDCK细胞中,采用G418加压筛选及有限稀释法克隆,获取稳定表达SLAM的MDCK细胞株.结果表明,成功构建了SLAM的真核表达载体pcDNA3.1/SLAM,并通过G418筛选获得了稳定表达SLAM的细胞系MDCK.

  17. Sorafenib in renal cell carcinoma.

    Science.gov (United States)

    Davoudi, Ehsan Taghizadeh; bin-Noordin, Mohamed Ibrahim; Javar, Hamid Akbari; Kadivar, Ali; Sabeti, Bahare

    2014-01-01

    Cancer is among most important causes of death in recent decades. Whoever the renal cell carcinoma incidence is low but it seems it is more complicated than the other cancers in terms of pathophysiology and treatments. The purpose of this work is to provide an overview and also deeper insight to renal cell carcinoma and the steps which have been taken to reach more specific treatment and target therapy, in this type of cancer by developing most effective agents such as Sorafenib. To achieve this goal hundreds of research paper and published work has been overviewed and due to limitation of space in a paper just focus in most important points on renal cell carcinoma, treatment of RCC and clinical development of Sorafenib. The information presented this paper shows the advanced of human knowledge to provide more efficient drug in treatment of some complicated cancer such as RCC in promising much better future to fight killing disease.

  18. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

    Science.gov (United States)

    Petersson, Fredrik; Grossmann, Petr; Hora, Milan; Sperga, Maris; Montiel, Delia Perez; Martinek, Petr; Gutierrez, Maria Evelyn Cortes; Bulimbasic, Stela; Michal, Michal; Branzovsky, Jindrich; Hes, Ondrej

    2013-07-01

    We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

  19. Guidelines on renal cell cancer

    NARCIS (Netherlands)

    Mickisch, G; Carballido, J; Hellsten, S; Schuize, H; Mensink, H

    2001-01-01

    Objectives., On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and. Follow Up of Renal. Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. Method: A sy

  20. [The Dutch guideline 'Renal cell carcinoma'].

    NARCIS (Netherlands)

    Osanto, S.; Bex, A.; Hulsbergen- van de Kaa, C.A.; Soetekouw, P.M.M.B.; Stemkens, D.

    2012-01-01

    The Dutch guideline 'Renal Cell Carcinoma' has been revised on the basis of new literature. With the assistance of the Netherlands Cancer Registry an assessment was made of the current care for patients with renal cell carcinoma. Renal cell carcinoma is a type of cancer for which knowledge of the ge

  1. MDCK细胞微载体悬浮培养放大工艺研究%A Study on Scale-up Process for Microcarrier Cultue of MDCK Cells Using Low Serum Medium

    Institute of Scientific and Technical Information of China (English)

    龚迪; 易小萍; 张元兴

    2012-01-01

    MDCK细胞对各种流感病毒具有高度敏感性,广泛应用于流感病毒的分离和疫苗制备.通过探索培养基中促进细胞贴壁的关键组分,并筛选水解物,开发了适合MDCK细胞生长的低血清培养基.发现钙、镁离子是细胞贴壁不可缺少的物质,麦麸水解物可以部分代替培养基中的血清.利用该低血清培养基,经过消化转移将MDCK细胞从5L反应器放大至25 L反应器,微载体上细胞贴附均匀、生长旺盛,25 L反应器中培养48 h细胞密度可达30.5×105 cells/ml.研究结果为工业规模反应器微载体悬浮培养MDCK细胞生产流感病毒奠定了基础.%Madin-Darby canine kidney ( MDCK) cells have been widely used for influenza virus isolation and vaccine production since they are susceptible to infection with various influenza virus strains. To develop a low serum medium for MDCK cells, critical components that affect cell adhesion and favorable hydrolyzate were investigated and selected separately. Calcium and magnesium ions were found indispensable to cell adhesion, and serum could be partially replaced by wheat hydrolyzate in medium. MDCK cells were digested from microcarriers in 5 L bioreactor and then scaled up to 25 L bioreactor. The results showed that the low serum medium well supported the growth of MDCK cells with favorable cell distributions, and the viable cell density reached 30.5 x 105 cells/ml 48 h after inoculation in 25 L bioreactor. The work provided the necessary basis for large-scale production of avian influenza virus using microcarrier-based MDCK cell culture system.

  2. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  3. Dynamic bio-adhesion of polymer nanoparticles on MDCK epithelial cells and its impact on bio-membranes, endocytosis and paracytosis

    Science.gov (United States)

    He, Bing; Yuan, Lan; Dai, Wenbing; Gao, Wei; Zhang, Hua; Wang, Xueqing; Fang, Weigang; Zhang, Qiang

    2016-03-01

    Nowadays, concern about the use of nanotechnology for biomedical application is unprecedentedly increasing. In fact, nanosystems applied for various potential clinical uses always have to cross the primary biological barrier consisting of epithelial cells. However, little is really known currently in terms of the influence of the dynamic bio-adhesion of nanosystems on bio-membranes as well as on endocytosis and transcytosis. This was investigated here using polymer nanoparticles (PNs) and MDCK epithelial cells as the models. Firstly, the adhesion of PNs on cell membranes was found to be time-dependent with a shift of both location and dispersion pattern, from the lateral adhesion of mainly mono-dispersed PNs initially to the apical coverage of the PN aggregate later. Then, it was interesting to observe in this study that the dynamic bio-adhesion of PNs only affected their endocytosis but not their transcytosis. It was important to find that the endocytosis of PNs was not a constant process. A GM1 dependent CDE (caveolae dependent endocytosis) pathway was dominant in the preliminary stage, followed by the co-existence of a CME (clathrin-mediated endocytosis) pathway for the PN aggregate at a later stage, in accordance with the adhesion features of PNs, suggesting the modification of PN adhesion patterns on the endocytosis pathways. Next, the PN adhesion was noticed to affect the structure of cell junctions, via altering the extra- and intra-cellular calcium levels, leading to the enhanced paracellular transport of small molecules, but not favorably enough for the obviously increased passing of PNs themselves. Finally, FRAP and other techniques all demonstrated the obvious impact of PN adhesion on the membrane confirmation, independent of the adhesion location and time, which might lower the threshold for the internalization of PNs, even their aggregates. Generally, these findings confirm that the transport pathway mechanism of PNs through epithelial cells is rather

  4. Calcium oxalate monohydrate crystals internalized into renal tubular cells are degraded and dissolved by endolysosomes.

    Science.gov (United States)

    Chaiyarit, Sakdithep; Singhto, Nilubon; Thongboonkerd, Visith

    2016-02-25

    Interaction between calcium oxalate crystals and renal tubular cells has been recognized as one of the key mechanisms for kidney stone formation. While crystal adhesion and internalization have been extensively investigated, subsequent phenomena (i.e. crystal degradation and dissolution) remained poorly understood. To explore these mechanisms, we used fluorescein isothiocyanate (FITC)-labelled calcium oxalate monohydrate (COM) crystals (1000 μg/ml of crystals/culture medium) to confirm crystal internalization into MDCK (Type II) renal tubular cells after exposure to the crystals for 1 h and to trace the internalized crystals. Crystal size, intracellular and extracellular fluorescence levels were measured using a spectrofluorometer for up to 48 h after crystal internalization. Moreover, markers for early endosome (Rab5), late endosome (Rab7) and lysosome (LAMP-2) were examined by laser-scanning confocal microscopy. Fluorescence imaging and flow cytometry confirmed that FITC-labelled COM crystals were internalized into MDCK cells (14.83 ± 0.85%). The data also revealed a reduction of crystal size in a time-dependent manner. In concordance, intracellular and extracellular fluorescence levels were decreased and increased, respectively, indicating crystal degradation/dissolution inside the cells and the degraded products were eliminated extracellularly. Moreover, Rab5 and Rab7 were both up-regulated and were also associated with the up-regulated LAMP-2 to form large endolysosomes in the COM-treated cells at 16-h after crystal internalization. We demonstrate herein, for the first time, that COM crystals could be degraded/dissolved by endolysosomes inside renal tubular cells. These findings will be helpful to better understand the crystal fate and protective mechanism against kidney stone formation.

  5. The effect of intracrystalline and surface-bound osteopontin on the attachment of calcium oxalate dihydrate crystals to Madin-Darby canine kidney (MDCK) cells in ultrafiltered human urine.

    Science.gov (United States)

    Thurgood, Lauren A; Sørensen, Esben S; Ryall, Rosemary L

    2012-04-01

    To determine the effects of intracrystalline (IC), surface-bound (SB) and combined IC + SB osteopontin (OPN) on the binding of urinary calcium oxalate dihydrate (COD) crystals to Madin-Darby canine kidney (MDCK-II) cells in ultrafiltered (UF) human urine. (14)C-oxalic acid-labelled urinary COD crystals containing IC OPN were generated in pooled UF human urine containing human milk OPN at concentrations of 0, 1.0 and 5.0 mg/L. Additional labelled crystals were nucleated from a separate sample of the same pooled UF urine, to which were later added the same amounts of protein to produce crystals with SB OPN. COD crystals with IC+SB OPN were prepared using a combination of both techniques. Control crystals were prepared in the absence of OPN. Crystals were incubated with MDCK-II cells for up to 180 min in UF urine adjusted to 8 mm Ca(2+). Binding values for individual concentrations at specific time points and overall differences between binding curves were compared using the Mann-Whitney U-test. Crystal morphology and attachment to the cells were confirmed using field emission scanning electron microscopy (FESEM). The sizes of crystals precipitated from UF urine in the presence of 0, 1 and 5 mg/L OPN were 21.9 µm, 19.3 µm and 16.5 µm, indicating that OPN had inhibited crystal growth in a dose-dependent fashion. Binding curves for control crystals were smooth, while those of the IC and IC+SB COD crystals associated with 1 and 5 mg/L OPN were bimodal, as were those of the 1 mg/L SB crystals. This suggests that OPN induces or potentiates a transient response that enables MDCK-II cells to release COD crystals after they have attached. Although OPN generally reduced the binding of urinary COD crystals to MDCK-II cells, at times it also appeared to mediate adhesion. It is possible therefore that OPN can reduce or increase crystal binding, and that our data represent the net effect of its opposing inhibitory or promotory properties. In UF urine, OPN inhibits the growth of

  6. Phorbol 12-myristate 13-acetate-induced endocytosis of the Na-K-2Cl cotransporter in MDCK cells is associated with a clathrin-dependent pathway.

    Science.gov (United States)

    Mykoniatis, Andreas; Shen, Le; Fedor-Chaiken, Mary; Tang, Jun; Tang, Xu; Worrell, Roger T; Delpire, Eric; Turner, Jerrold R; Matlin, Karl S; Bouyer, Patrice; Matthews, Jeffrey B

    2010-01-01

    In secretory epithelial cells, the basolateral Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) plays a major role in salt and fluid secretion. Our laboratory has identified NKCC1 surface expression as an important regulatory mechanism for Cl(-) secretion in the colonic crypt cell line T84, a process also present in native human colonic crypts. We previously showed that activation of protein kinase C (PKC) by carbachol and phorbol 12-myristate 13-acetate (PMA) decreases NKCC1 surface expression in T84 cells. However, the specific endocytic entry pathway has not been defined. We used a Madin-Darby canine kidney (MDCK) cell line stably transfected with enhanced green fluorescent protein (EGFP)-NKCC1 to map NKCC1 entry during PMA exposure. At given times, we fixed and stained the cells with specific markers (e.g., dynamin II, clathrin heavy chain, and caveolin-1). We also used chlorpromazine, methyl-beta-cyclodextrin, amiloride, and dynasore, blockers of the clathrin, caveolin, and macropinocytosis pathways and the vesicle "pinchase" dynamin, respectively. We found that PMA caused dose- and time-dependent NKCC1 endocytosis. After 2.5 min of PMA exposure, approximately 80% of EGFP-NKCC1 endocytic vesicles colocalized with clathrin and approximately 40% colocalized with dynamin II and with the transferrin receptor, the uptake of which is also mediated by clathrin-coated vesicles. We did not observe significant colocalization of EGFP-NKCC1 endocytic vesicles with caveolin-1, a marker of the caveolae-mediated endocytic pathway. We quantified the effect of each inhibitor on PMA-induced EGFP-NKCC1 endocytosis and found that only chlorpromazine and dynasore caused significant inhibition compared with the untreated control (61% and 25%, respectively, at 2.5 min). Together, these results strongly support the conclusion that PMA-stimulated NKCC1 endocytosis is associated with a clathrin pathway.

  7. Tumor Seeding With Renal Cell Carcinoma After Renal Biopsy

    OpenAIRE

    M.F.B. Andersen; Norus, T.P.

    2016-01-01

    Tumor seeding following biopsy of renal cell carcinoma is extremely rare with an incidence of 1:10.000. In this paper two cases with multiple recurrent RRC metastasis in the biopsy tract following biopsy of renal tumor is presented and the current literature is shortly discussed.

  8. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  9. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  10. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  11. The Blood-Brain Barrier Permeability of Lignans and Malabaricones from the Seeds of Myristica fragrans in the MDCK-pHaMDR Cell Monolayer Model

    Directory of Open Access Journals (Sweden)

    Ni Wu

    2016-01-01

    Full Text Available The blood-brain barrier (BBB permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with Papp values at 10−8–10−6 cm/s; those of 8-O-4′-neolignan and tetrahydrofuran-lignan were at 10−6–10−5 cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their Papp values were at 10−8–10−7 cm/s. To 5-methoxy-dehydrodiisoeugenol (2, erythro-2-(4-allyl-2,6-dimethoxyphenoxy-1-(3,4-dimethoxyphenyl-propan-1-ol acetate (6, verrucosin (8, and nectandrin B (9, an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1, myrislignan (7 and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg.

  12. [Intrascrotal metastasis in a renal cell carcinoma].

    Science.gov (United States)

    Calleja Escudero, J; Pascual Samaniego, M; Martín Blanco, S; de Castro Olmedo, C; Gonzalo, V; Fernández del Busto, E

    2004-04-01

    The present article reports a case of intrascrotal metastasis of renal adenocarcinoma. This is an unusual case. A 66-year-old male patient undewent right radical nephrectomy and cavotomy for renal cell carcinoma with renal vein infiltration and thrombus in cava. Six months later the patient present with a nodulous enlargement intrascrotal and roots of penis. And he died 15 moths after nephrectomy. Usually intrascrotal metastases are a late event in the course after detection of a renal carcinoma.

  13. Functional rescue of a kidney anion exchanger 1 trafficking mutant in renal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Carmen Y S Chu

    Full Text Available Mutations in the SLC4A1 gene encoding the anion exchanger 1 (AE1 can cause distal renal tubular acidosis (dRTA, a disease often due to mis-trafficking of the mutant protein. In this study, we investigated whether trafficking of a Golgi-retained dRTA mutant, G701D kAE1, or two dRTA mutants retained in the endoplasmic reticulum, C479W and R589H kAE1, could be functionally rescued to the plasma membrane of Madin-Darby Canine Kidney (MDCK cells. Treatments with DMSO, glycerol, the corrector VX-809, or low temperature incubations restored the basolateral trafficking of G701D kAE1 mutant. These treatments had no significant rescuing effect on trafficking of the mis-folded C479W or R589H kAE1 mutants. DMSO was the only treatment that partially restored G701D kAE1 function in the plasma membrane of MDCK cells. Our experiments show that trafficking of intracellularly retained dRTA kAE1 mutants can be partially restored, and that one chemical treatment rescued both trafficking and function of a dRTA mutant. These studies provide an opportunity to develop alternative therapeutic solutions for dRTA patients.

  14. Activation of the ALK-5 Pathway is not per se Sufficient for the Antiproliferative Effect of TGF-β1 on Renal Tubule Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Omar García-Sánchez

    2015-10-01

    Full Text Available Background/Aims: Defective tissue repair underlies renal tissue degeneration during chronic kidney disease (CKD progression. Unbalanced presence of TGF-β opposes effective cell proliferation and differentiation processes, necessary to replace damaged epithelia. TGF-β also retains arrested cells in a fibrotic phenotype responsible for irreversible scarring. In order to identify prospective molecular targets to prevent the effect of TGF-β during CKD, we studied the signaling pathways responsible for the antiproliferative effect of this cytokine. Methods: Tubule epithelial HK2 and MDCK cells were treated with TGF-β (or not as control to study cell proliferation (by MTT, cell signaling (by Western blot, cell cycle (by flow cytometry and apoptosis (DNA fragmentation. Results: TGF-β fully activates the ALK-5 receptor pathway, whereas it has no effect on the ALK-1 and MAPK pathways in both HK2 and MDCK cells. Interestingly, TGF-β exerts an antiproliferative effect only on MDCK cells, through a cytostatic effect in G0/G1. Inhibition of the ALK-5 pathway with SB431542 prevents the cytostatic effect of TGF-β on MDCK cells. Conclusion: Activation of the ALK-5 pathway is not sufficient for the antiproliferative effect of TGF-β. The presence of undetermined permissive conditions or absence of undetermined inhibitory conditions seems to be necessary for this effect. The ALK-5 pathway appears to provide targets to modulate fibrosis, but further research is necessary to identify critical circumstances allowing or inhibiting its role at modulating tubule epithelial cell proliferation and tubule regeneration in the context of CKD progression.

  15. Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif

    DEFF Research Database (Denmark)

    Jespersen, Thomas; Rasmussen, Hanne B; Grunnet, Morten;

    2004-01-01

    KCNQ1 potassium channels are expressed in many epithelial tissues as well as in the heart. In epithelia KCNQ1 channels play an important role in salt and water transport and the channel has been reported to be located apically in some cell types and basolaterally in others. Here we show that KCNQ...

  16. Basement membrane and interstitial proteoglycans produced by MDCK cells correspond to those expressed in the kidney cortex

    DEFF Research Database (Denmark)

    Erickson, A C; Couchman, J R

    2001-01-01

    Multiple proteoglycans (PGs) are present in all basement membranes (BM) and may contribute to their structure and function, but their effects on cell behavior are not well understood. Their postulated functions include: a structural role in maintaining tissue histoarchitecture, or aid in selectiv...

  17. MDCK cell line with inducible allele B NS1 expression propagates deINS1 inflenza virus to high titres

    NARCIS (Netherlands)

    Wielink, van R.; Harmsen, M.M.; Martens, D.E.; Peeters, B.P.H.; Wijffels, R.H.; Moormann, R.J.M.

    2011-01-01

    Influenza A viruses lacking the gene encoding the non-structural NS1 protein (delNS1) have potential use as live attenuated vaccines. However, due to the lack of NS1, virus replication in cell culture is considerably reduced, prohibiting commercial vaccine production. We therefore established two st

  18. Effect of FCCP on tight junction permeability and cellular distribution of ZO-1 protein in epithelial (MDCK) cells.

    Science.gov (United States)

    Li, C X; Poznansky, M J

    1990-12-14

    The effect of the uncoupler of oxidative phosphorylation, FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone), on the tight junction of Madin-Darby canine kidney cells was examined. FCCP induced an abrupt decrease in the transepithelial electrical resistance of the confluent monolayers over a period of 20 s. When FCCP was withdrawn from the incubation medium, the monolayer resistance recovered to close to the original level in less than 2 h. Staining of the tight junction-associated protein ZO-1 showed that the changes in transepithelial electrical resistance were accompanied by a diffusing of the protein away from cell peripheries and a reconcentration to the tight junction areas following resistance recovery. Intracellular pH was decreased by FCCP on a similar time-scale with no obvious changes in ATP levels over this time-course. These data suggest that the uncoupler FCCP has a profound effect on tight junction permeability and cellular distribution of the tight junction protein ZO-1 in the epithelial cells and that it probably acts by breaking down proton gradients and altering intracellular pH.

  19. [Renal cell carcinoma secondary to tuberculous nephritis].

    Science.gov (United States)

    El Mejjad, Amine; Fekak, Hamid; Debbagh, Adili; Joual, Abdenbi; Bennani, Saad; El Mrini, Mohamed

    2005-04-01

    The combination of renal tuberculosis and renal cancer is rare. The authors report the case of a patient who was followed for multifocal pulmonary, hepatic and renal tuberculosis. The diagnosis of associated renal tumour was raised in the presence of suggestive radiological images. Tumourectomy was performed after tuberculostatic therapy, and histological examination revealed renal cell carcinoma associated with caseo-follicular tuberculous granulomas. The outcome was favourable after a follow-up of 2 years. The objective of this study is to analyse the pathogenesis, diagnostic features and treatment modalities of this exceptional combination.

  20. Ubiquitination regulates the plasma membrane expression of renal UT-A urea transporters.

    Science.gov (United States)

    Stewart, Gavin S; O'Brien, Jennifer H; Smith, Craig P

    2008-07-01

    The renal UT-A urea transporters UT-A1, UT-A2, and UT-A3 are known to play an important role in the urinary concentrating mechanism. The control of the cellular localization of UT-A transporters is therefore vital to overall renal function. In the present study, we have investigated the effect of ubiquitination on UT-A plasma membrane expression in Madin-Darby canine kidney (MDCK) cell lines expressing each of the three renal UT-A transporters. Inhibition of the ubiquitin-proteasome pathway caused an increase in basal transepithelial urea flux across MDCK-rat (r)UT-A1 and MDCK-mouse (m)UT-A2 monolayers (P UT-A transporter expression in the plasma membrane (P UT-A3 expression in the plasma membrane (P UT-A urea transporters, but that this is not the mechanism primarily used by vasopressin to produce its physiological effects.

  1. The Heidelberg classification of renal cell tumours

    NARCIS (Netherlands)

    Kovacs, G; Akhtar, M; Beckwith, BJ; Bugert, P; Cooper, CS; Delahunt, B; Eble, JN; Fleming, S; Ljungberg, B; Medeiros, LJ; Moch, H; Reuter, VE; Ritz, E; Roos, G; Schmidt, D; Srigley, [No Value; Storkel, S; VandenBerg, E; Zbar, B

    1997-01-01

    This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996, The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic t

  2. Renal cell carcinoma in functional renal graft: Toward ablative treatments.

    Science.gov (United States)

    Tillou, Xavier; Guleryuz, Kerem; Collon, Sylvie; Doerfler, Arnaud

    2016-01-01

    The occurrence of a kidney transplant tumor is a rare but serious issue with a double risk: the return to dialysis and the development of metastatic cancer. Publications on this topic are mainly case reports. The purpose of this review was to report an exhaustive literature review of functional graft renal cell carcinomas to highlight the impact of tumors on the renal graft outcomes. 201 de novo renal carcinomas in functional renal grafts from 69 publications were included. Incidence was estimated at 0.18%. Graft tumors were mostly asymptomatic (85.9%). Whatever the discovery circumstances of graft tumors, they were mostly documented by graft ultrasounds supplemented by CT-scanning or MR imaging. Nephron sparing surgery (95 patients) was the first treatment performed followed by radiofrequency ablation (38 patients) and cryotherapy (10 patients). The most common tumor graft histology was clear cell carcinoma (46.4%), followed by papillary carcinoma (43.7%). Specific mortality was 2.9% with 6 deaths. Renal graft cell carcinoma is a rare pathology with a low specific death. When possible, conservative treatment should be the first choice. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Ins(1,4,5)P{sub 3} facilitates ATP accumulation via phosphocreatine/creatine kinase in the endoplasmic reticulum extracted from MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jing [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Department of Dental Implantology, School of Stomatology, Tongji University, Shanghai 200072 (China); Ogata, Shigenori [Joint Laboratory for Frontier Medical Science, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Segawa, Masaru [Central Laboratory for Pathology and Morphology, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Usune, Sadaharu [Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Zhao, Yumei [Department of Pediatric Dentistry, School of Dentistry of Shanghai Tongji University, Shanghai 200072 (China); Katsuragi, Takeshi, E-mail: katsurag@fukuoka-u.ac.jp [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan)

    2010-07-02

    So far, the content and accumulation of ATP in isolated endoplasmic reticulum (ER) are little understood. First, we confirmed using electron microscopic and Western blotting techniques that the samples extracted from MDCK cells are endoplasmic reticulum (ER). The amounts of ATP in the extracted ER were measured from the filtrate after a spinning down of ultrafiltration spin column packed with ER. When the ER sample (5 {mu}g) after 3 days freezing was suspended in intracellular medium (ICM), 0.1% Triton X and ultrapure water (UPW), ATP amounts from the ER with UPW were the highest and over 10 times compared with that from the control with ICM, indicating that UPW is the most effective tool in destroying the ER membrane. After a 10-min-incubation with ICM containing phosphocreatine (PCr)/creatine kinase (CK) of the fresh ER. ATP amounts in the filtrate obtained by spinning down were not changed from that in the control (no PCr/CK). However, ATP amounts in the filtrate from the second spinning down of the ER (treated with PCr/CK) suspended in UPW became over 10-fold compared with the control. When 1 {mu}M inositol(1,4,5)trisphosphate (Ins(1,4,5)P{sub 3}) was added in the incubation medium (ICM with PCr/CK), ATP amounts from the filtrate after the second spinning down were further enhanced around three times. This enhancement was almost canceled by Ca{sup 2+}-removal from ICM and by adding thapsigargin, a Ca{sup 2+}-ATPase inhibitor, but not by 2-APB and heparin, Ins(1,4,5)P{sub 3} receptor antagonists. Administration of 500 {mu}M adenosine to the incubation medium (with PCr/CK) failed to enhance the accumulation of ATP in the ER. These findings suggest that the ER originally contains ATP and ATP accumulation in the ER is promoted by PCr/CK and Ins(1,4,5)P{sub 3}.

  4. Nephrotoxicity of Bence-Jones proteins: interference in renal epithelial cell acidification

    Directory of Open Access Journals (Sweden)

    Nicastri A.L.

    2002-01-01

    Full Text Available The aim of the present study was to evaluate the acidification of the endosome-lysosome system of renal epithelial cells after endocytosis of two human immunoglobulin lambda light chains (Bence-Jones proteins, BJP obtained from patients with multiple myeloma. Renal epithelial cell handling of two BJP (neutral and acidic BJP was evaluated by rhodamine fluorescence. Renal cells (MDCK were maintained in culture and, when confluent, were incubated with rhodamine-labeled BJP for different periods of time. Photos were obtained with a fluorescence microscope (Axiolab-Zeiss. Labeling density was determined on slides with a densitometer (Shimadzu Dual-Wavelength Flying-Spot Scanner CS9000. Endocytosis of neutral and acidic BJP was correlated with acidic intracellular compartment distribution using acridine orange labeling. We compared the pattern of distribution after incubation of native neutral and acidic BJP and after complete deglycosylation of BJP by periodate oxidation. The subsequent alteration of pI converted neutral BJP to acidic BJP. There was a significant accumulation of neutral BJP in endocytic structures, reduced lysosomal acidification, and a diffuse pattern of acidification. This pattern was reversed after total deglycosylation and subsequent alteration of the pI to an acidic BJP. We conclude that the physicochemical characteristics of BJP interfere with intracellular acidification, possibly explaining the strong nephrotoxicity of neutral BJP. Lysosomal acidification is fundamental for adequate protein processing and catabolism.

  5. Cell adhesion signalling in acute renal failure

    NARCIS (Netherlands)

    Qin, Yu

    2011-01-01

    Acute renal failure (ARF) remains a severe clinical problem with high mortality. Little progress has been made over the past two decades in preventing renal injury or reducing mortality. This thesis describes the research to investigate cell adhesion alterations during the pathopysiology of both isc

  6. Antioxidant Pre-Treatment Reduces the Toxic Effects of Oxalate on Renal Epithelial Cells in a Cell Culture Model of Urolithiasis

    Directory of Open Access Journals (Sweden)

    Tomislav Kizivat

    2017-01-01

    Full Text Available Urolithiasis is characterized by the formation and retention of solid crystals within the urinary tract. Kidney stones are mostly composed of calcium oxalate, which predominantly generates free radicals that are toxic to renal tubular cells. The aim of the study is to explore possible effects of antioxidant pre-treatment on inhibition of oxidative stress. Three cell lines were used as in vitro model of urolithiasis: MDCK I, MDCK II and LLC-PK1. Oxidative stress was induced by exposure of cells to sodium oxalate in concentration of 8 mM. In order to prevent oxidative stress, cells were pre-treated with three different concentrations of l-arginine and vitamin E. Oxidative stress was evaluated by determining the expression of superoxide dismutase (SOD, osteopontin (OPN, and by the concentration of glutathione (GSH. In all three cell lines, pre-treatment of antioxidants increased cell survival. Positive correlation of SOD and OPN expression as well as GSH concentration was observed in all groups of cells. Our results indicate that an antioxidant pre-treatment with l-arginine and vitamin E is able to hamper oxalate-induced oxidative stress in kidney epithelial cells and as such could play a role in prevention of urolithiasis.

  7. The anti-epileptic drug substance vigabatrin inhibits taurine transport in intestinal and renal cell culture models

    DEFF Research Database (Denmark)

    Plum, Jakob Munk; Nøhr, Martha Kampp; Hansen, Steen H

    2014-01-01

    , such evidence does not preclude the involvement of other transporters. The aim of the present study was, therefore, to investigate if vigabatrin interacts with taurine transport. The uptake of taurine was measured in intestinal human Caco-2 and canine MDCK cell monolayers in the absence or presence of amino...... acids such as GABA and vigabatrin. Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to 34±3 and 53±2%, respectively, at a concentration of 30mM. In Caco-2 cells the uptake of vigabatrin under neutral pH conditions is concentration-dependent and saturable with a Km-value of 27mM (log......Km is 1.43±0.09). In conclusion, the present study shows that vigabatrin was able to inhibit the uptake of taurine in intestinal and renal cell culture models. Furthermore, uptake of vigabatrin in Caco-2 cells under neutral pH conditions was concentration-dependent and saturable and suggesting...

  8. Renal atrophy after stereotactic body radiotherapy for renal cell carcinoma.

    Science.gov (United States)

    Yamamoto, Takaya; Kadoya, Noriyuki; Takeda, Ken; Matsushita, Haruo; Umezawa, Rei; Sato, Kiyokazu; Kubozono, Masaki; Ito, Kengo; Ishikawa, Yojiro; Kozumi, Maiko; Takahashi, Noriyoshi; Katagiri, Yu; Onishi, Hiroshi; Jingu, Keiichi

    2016-05-26

    Renal atrophy is observed in an irradiated kidney. The aim of this study was to determine dose-volume histogram parameters and other factors that predict renal atrophy after 10-fraction stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC). A total of 14 patients (11 males, 3 females) who received SBRT for RCC at Tohoku University Hospital between April 2010 and February 2014 were analyzed. The median serum creatinine level was 1.1 mg/dl and two patients had a single kidney. Nine patients were implanted with fiducial markers. The median tumor diameter was 30 mm. SBRT was delivered at 70 Gy in 10 fractions for 7 tumors, at 60 Gy in 10 fractions for 2 tumors, and at 50 Gy in 10 fractions for 5 tumors with 6 and/or 15 MV X-ray using 5 to 8 multi-static beams. Renal atrophy was assessed using post-SBRT CT images after 12-24 months intervals. Correlations were examined by Spearman rank correlation analysis. Differences between two groups were evaluated by the Mann-Whitney test, and pairwise comparisons were made by the Wilcoxon signed-rank test. The median tumor volume shrunk from 14.8 cc to 10.6 cc (p = 0.12), and the median irradiated kidney volume changed from 160.4 cc to 137.1 cc (p atrophy (p = 0.02). Significant renal atrophic change was observed. Dose distribution of SBRT at 20-30 Gy had a strong correlation with renal atrophy when irradiation was performed in 10 fractions.

  9. Apigenin inhibits renal cell carcinoma cell proliferation.

    Science.gov (United States)

    Meng, Shuai; Zhu, Yi; Li, Jiang-Feng; Wang, Xiao; Liang, Zhen; Li, Shi-Qi; Xu, Xin; Chen, Hong; Liu, Ben; Zheng, Xiang-Yi; Xie, Li-Ping

    2017-03-21

    Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC.

  10. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... 2015 2014 2013 2012 Media Resources Media Contacts Multicultural Media ... This page lists cancer drugs approved by the Food and Drug Administration (FDA) for kidney (renal cell) cancer. The list ...

  11. Sunitinib benefits patients with renal cell carcinoma

    Science.gov (United States)

    Findings from clinical trial patients with metastatic renal cell carcinoma, a common kidney cancer, show they did not have accelerated tumor growth after treatment with sunitinib, in contrast to some study results in animals.

  12. Isolated pleural metastases from renal cell carcionoma

    DEFF Research Database (Denmark)

    Eckardt, Jens; Ladegaard, Lars; Licht, Peter Bjorn

    2011-01-01

    A 71-year-old female was referred with three right-sided intrathoracic tumours. In 2003, she underwent radical left nephrectomy for renal cell cancer (RCC) clinical stage 1. She was since followed at her local hospital with annual computed tomography (CT)-scans during the first five years and did....... Histology demonstrated metastases from RCC which apparently can reach the parietal pleura without lung metastases. Keywords: Pleural metastasis; Renal cell cancer....

  13. Cardiac metastasis from a renal cell carcinoma

    OpenAIRE

    AlGhamdi, Abdulaziz; Tam, James

    2006-01-01

    A 59-year-old man developed an episode of syncope while he was driving. This resulted in a motor vehicle accident, and the patient sustained an open fracture of the left femur. Biopsy of the left femur fracture showed a metastastic renal cell carcinoma, and echocardiography revealed a right ventricular mass without contiguous vena caval or right atrial involvement. This is one of the few reported cases of renal cell carcinoma associated with syncope as an initial symptom.

  14. Slow spontaneous [Ca2+]i oscillations reflect nucleotide release from renal epithelia

    DEFF Research Database (Denmark)

    Geyti, Christine Stride; Odgaard, Elvin V. P.; Overgaard, Morten Thaarup

    2008-01-01

    nucleotide signalling. In this study, fluo-4 loaded Madin-Darby canine kidney (MDCK) cells are used as a model for quantification and characterisation of spontaneous [Ca(2+)](i) increases in renal epithelia. Spontaneous [Ca(2+)](i) increases occurred randomly as single cell events. During an observation...

  15. Renal Cell Carcinoma Metastasized to Pagetic Bone.

    Science.gov (United States)

    Ramirez, Ashley; Liu, Bo; Rop, Baiywo; Edison, Michelle; Valente, Michael; Burt, Jeremy

    2016-01-01

    Paget's disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget's disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget's disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget's disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget's disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget's disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone.

  16. Percutaneous Cryoablation for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tsitskari Maria

    2015-06-01

    Full Text Available Renal cell carcinoma (RCC is the most common type of kidney cancer in adults. Nephron sparing resection (partial nephrectomy has been the “gold standard” for the treatment of resectable disease. With the widespread use of cross sectional imaging techniques, more cases of renal cell cancers are detected at an early stage, i.e. stage 1A or 1B.  This has provided an impetus for expanding the nephron sparing options and especially, percutaneous ablative techniques.  Percutaneous ablation for RCC is now performed as a standard therapeutic nephron-sparing option in patients who are poor candidates for resection or when there is a need to preserve renal function due to comorbid conditions, multiple renal cell carcinomas, and/or heritable renal cancer syndromes. During the last few years, percutaneous cryoablation has been gaining acceptance as a curative treatment option for small renal cancers. Clinical studies to date indicate that cryoablation is a safe and effective therapeutic method with acceptable short and long term outcomes and with a low risk, in the appropriate setting.  In addition it seems to offer some advantages over radio frequency ablation (RFA and other thermal ablation techniques for renal masses.

  17. An MDCK cell culture-derived formalin-inactivated influenza virus whole-virion vaccine from an influenza virus library confers cross-protective immunity by intranasal administration in mice.

    Science.gov (United States)

    Haredy, Ahmad M; Takenaka, Nobuyuki; Yamada, Hiroshi; Sakoda, Yoshihiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Omasa, Takeshi; Ohtake, Hisao; Mori, Yasuko; Kida, Hiroshi; Yamanishi, Koichi; Okamoto, Shigefumi

    2013-07-01

    It is currently impossible to predict the next pandemic influenza virus strain. We have thus established a library of influenza viruses of all hemagglutinin and neuraminidase subtypes and their genes. In this article, we examine the applicability of a rapid production model for the preparation of vaccines against emerging pandemic influenza viruses. This procedure utilizes the influenza virus library, cell culture-based vaccine production, and intranasal administration to induce a cross-protective immune response. First, an influenza virus reassortant from the library, A/duck/Hokkaido/Vac-3/2007 (H5N1), was passaged 22 times (P22) in Madin-Darby canine kidney (MDCK) cells. The P22 virus had a titer of >2 ×10(8) PFU/ml, which was 40 times that of the original strain, with 4 point mutations, which altered amino acids in the deduced protein sequences encoded by the PB2 and PA genes. We then produced a formalin-inactivated whole-virion vaccine from the MDCK cell-cultured A/duck/Hokkaido/Vac-3/2007 (H5N1) P22 virus. Intranasal immunization of mice with this vaccine protected them against challenges with lethal influenza viruses of homologous and heterologous subtypes. We further demonstrated that intranasal immunization with the vaccine induced cross-reactive neutralizing antibody responses against the homotypic H5N1 influenza virus and its antigenic variants and cross-reactive cell-mediated immune responses to the homologous virus, its variants within a subtype, and even an influenza virus of a different subtype. These results indicate that a rapid model for emergency vaccine production may be effective for producing the next generation of pandemic influenza virus vaccines.

  18. Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model.

    Science.gov (United States)

    Hu, Peng-Yi; Liu, Dan; Zheng, Qin; Wu, Qing; Tang, Yu; Yang, Ming

    2016-03-02

    The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10(-6) to 0.705 × 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.

  19. Renal stem cells: fact or science fiction?

    Science.gov (United States)

    McCampbell, Kristen K; Wingert, Rebecca A

    2012-06-01

    The kidney is widely regarded as an organ without regenerative abilities. However, in recent years this dogma has been challenged on the basis of observations of kidney recovery following acute injury, and the identification of renal populations that demonstrate stem cell characteristics in various species. It is currently speculated that the human kidney can regenerate in some contexts, but the mechanisms of renal regeneration remain poorly understood. Numerous controversies surround the potency, behaviour and origins of the cell types that are proposed to perform kidney regeneration. The present review explores the current understanding of renal stem cells and kidney regeneration events, and examines the future challenges in using these insights to create new clinical treatments for kidney disease.

  20. Renal calculus complicated with squamous cell carcinoma of renal pelvis: Report of two cases.

    Science.gov (United States)

    Xiao, Jiantao; Lei, Jun; He, Leye; Yin, Guangming

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC.

  1. An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma

    National Research Council Canada - National Science Library

    Hakimi, A Ari; Reznik, Ed; Lee, Chung-Han; Creighton, Chad J; Brannon, A Rose; Luna, Augustin; Aksoy, B Arman; Liu, Eric Minwei; Shen, Ronglai; Lee, William; Chen, Yang; Stirdivant, Steve M; Russo, Paul; Chen, Ying-Bei; Tickoo, Satish K; Reuter, Victor E; Cheng, Emily H; Sander, Chris; Hsieh, James J

    2016-01-01

    .... We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response...

  2. Alpha-enolase on apical surface of renal tubular epithelial cells serves as a calcium oxalate crystal receptor

    Science.gov (United States)

    Fong-Ngern, Kedsarin; Thongboonkerd, Visith

    2016-10-01

    To search for a strategy to prevent kidney stone formation/recurrence, this study addressed the role of α-enolase on apical membrane of renal tubular cells in mediating calcium oxalate monohydrate (COM) crystal adhesion. Its presence on apical membrane and in COM crystal-bound fraction was confirmed by Western blotting and immunofluorescence staining. Pretreating MDCK cells with anti-α-enolase antibody, not isotype-controlled IgG, dramatically reduced cell-crystal adhesion. Immunofluorescence staining also confirmed the direct binding of purified α-enolase to COM crystals at {121} > {100} > {010} crystal faces. Coating COM crystals with urinary proteins diminished the crystal binding capacity to cells and purified α-enolase. Moreover, α-enolase selectively bound to COM, not other crystals. Chemico-protein interactions analysis revealed that α-enolase interacted directly with Ca2+ and Mg2+. Incubating the cells with Mg2+ prior to cell-crystal adhesion assay significantly reduced crystal binding on the cell surface, whereas preincubation with EDTA, a divalent cation chelator, completely abolished Mg2+ effect, indicating that COM and Mg2+ competitively bind to α-enolase. Taken together, we successfully confirmed the role of α-enolase as a COM crystal receptor to mediate COM crystal adhesion at apical membrane of renal tubular cells. It may also serve as a target for stone prevention by blocking cell-crystal adhesion and stone nidus formation.

  3. Targeted Therapy for Renal Cell Carcinoma: a Prospective study

    Directory of Open Access Journals (Sweden)

    Robin Joshi

    2015-06-01

    Conclusions: In our cohort, use of sunitinib showed similar outcome to previously published articles. Our study supports the use of sunitinib in metastatic renal cell carcinoma. Keywords: metastatic renal cell carcinoma; sunitinib; tyrosine kinase inhibitor.

  4. Sunitinib for advanced renal cell cancer

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2008-03-01

    Full Text Available Chris CoppinBC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Renal cell cancer has been refractory to drug therapy in the large majority of patients. Targeted agents including sunitinib have been intensively evaluated in renal cell cancer over the past 5 years. Sunitinib is an oral small molecule inhibitor of several targets including multiple tyrosine kinase receptors of the angiogenesis pathway. This review surveys the rationale, development, validation, and clinical use of sunitinib that received conditional approval for use in North America and Europe in 2006. In patients with the clear-cell subtype of renal cell cancer and metastatic disease with good or moderate prognostic factors for survival, sunitinib 50 mg for 4 weeks of a 6-week cycle provides superior surrogate and patient-reported outcomes when compared with interferon-alfa, the previous commonly used first-line drug. Overall survival has not yet shown improvement over interferon and is problematic because of patient crossover from the control arm to sunitinib at disease progression. Toxicity is significant but manageable with experienced monitoring. Sunitinib therapy is an important step forward for this condition. High cost and limited efficacy support the ongoing search for further improved therapy.Keywords: renal cell cancer, targeted therapy, sunitinib

  5. The epidemiology of renal cell carcinoma

    NARCIS (Netherlands)

    Ljungberg, B.; Campbell, S.C.; Cho, H.Y.; Jacqmin, D.; Lee, J.E.; Weikert, S.; Kiemeney, L.A.L.M.

    2011-01-01

    CONTEXT: Kidney cancer is among the 10 most frequently occurring cancers in Western communities. Globally, about 270 000 cases of kidney cancer are diagnosed yearly and 116 000 people die from the disease. Approximately 90% of all kidney cancers are renal cell carcinomas (RCC). OBJECTIVE: The causes

  6. Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K

    2015-01-01

    BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology t...

  7. Oxidative stress and apoptosis in intrinsic renal cell populations - an in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Gobe, G.C.; Hogg, N.; Schoch, E.; James, M.; Willgoss, D.; Endre, Z. [University of Queensland, Brisbane, QLD (Australia)

    1996-12-31

    The authors have been studying the interaction between incidence of apoptosis and expression of selected oncogenes and cytokines in an in vivo rat model of ischaemia-reperfusion injury. The ischaemia itself, and the reperfusion, induce oxidative damage to the tissues, including damage from oxygen-derived free radicals. The scenario is therefore similar to radiation-induced injury. The proximal nephron segments, especially the pars recta, are usually acutely sensitive to ischaemia-reperfusion injury, undergoing necrosis in preference to apoptosis. A hypothesis was formed that Bcl-2 protection of the distal nephron, a segment of the nephron known as a reservoir for many growth factors or cytokines, allows increased production of growth factors during oxidative stress, which then act in a paracrine manner to protect the nearby proximal tubule. To test this hypothesis, an in vitro model of oxidative stress was used on either distal (Madin Derby Canine Kidney, MDCK) or proximal (human kidney-2, HK-2) established renal cell lines. We grow the cells as `coverslip cultures` in 12-well plates in Dulbecco`s Modified Eagle`s Medium or serum free medium. The treatments used are either hydrogen peroxide (a gradation of concentrations from 1mM to 50 mM), tumour necrosis factor-alpha (TNF-alpha) or hypoxia, as inducers of oxidative stress. The parameters analysed in the present study were (i) cell death (apoptosis or necrosis, using histology, in situ end labelling, and electron microscopy) (ii) cell proliferation and (iii) Bcl-2 expression (immunohistochemistry). It was found that all treatments increase levels of apoptosis in both cell lines, and TNF-alpha also causes increased cell proliferation. At the higher concentrations of hydrogen peroxide however, the HK-2 (proximal) cells have more of a tendency to undergo necrosis than do the MDCK (distal) cells, mimicking the in vivo situation. Bcl-2 expression is low in both cell lines, and does not appear to be affected by the

  8. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  9. Anoctamin 1 induces calcium-activated chloride secretion and proliferation of renal cyst-forming epithelial cells.

    Science.gov (United States)

    Buchholz, Bjoern; Faria, Diana; Schley, Gunnar; Schreiber, Rainer; Eckardt, Kai-Uwe; Kunzelmann, Karl

    2014-05-01

    Polycystic kidney diseases are characterized by multiple bilateral renal cysts that gradually enlarge and lead to a decline in renal function. Cyst enlargement is driven by transepithelial chloride secretion, stimulated by enhanced levels of cyclic adenosine monophosphate, which activates apical cystic fibrosis transmembrane conductance regulator chloride channels. However, chloride secretion by calcium-dependent chloride channels, activated through stimulation of purinergic receptors, also has a major impact. To identify the molecular basis of calcium-dependent chloride secretion in cyst expansion, we determined the role of anoctamin 1 and 6, two recently discovered calcium-activated chloride channels both of which are expressed in epithelial cells. We found that anoctamin 1, which plays a role in epithelial fluid secretion and proliferation, is strongly expressed in principal-like MDCK cells (PLCs) forming cysts within a collagen matrix, in an embryonic kidney cyst model, and in human autosomal dominant polycystic kidney disease tissue. Knockdown of anoctamin 1 but not anoctamin 6 strongly diminished the calcium-dependent chloride secretion of PLCs. Moreover, two inhibitors of anoctamin ion channels, tannic acid and a more selective inhibitor of anoctamin 1, significantly inhibited PLC cyst growth and cyst enlargement in an embryonic kidney cyst model. Knockdown of ANO1 by morpholino analogs also attenuated embryonic cyst growth. Thus, calcium-activated chloride secretion by anoctamin 1 appears to be a crucial component of renal cyst growth.

  10. The function of tight junctions in maintaining differences in lipid composition between the apical and the basolateral cell surface domains of MDCK cells

    NARCIS (Netherlands)

    van Meer, G.|info:eu-repo/dai/nl/068570368; Simons, K.

    1986-01-01

    Tight junctions in epithelial cells have been postulated to act as barriers inhibiting lateral diffusion of lipids and proteins between the apical and basolateral plasma membrane domains. To study the fence function of the tight junction in more detail, we have fused liposomes containing the

  11. Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure

    OpenAIRE

    George, Sunil K.; Abolbashari, Mehran; Jackson, John D.; AbouShwareb, Tamer; Atala, Anthony; James J. Yoo

    2016-01-01

    Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (...

  12. Composite renal cell carcinoma with clear cell renal cell carcinomatous and carcinoid tumoral elements: a first case report.

    Science.gov (United States)

    Bressenot, A; Delaunay, C; Gauchotte, G; Oliver, A; Boudrant, G; Montagne, K

    2010-02-01

    Renal endocrine tumours are extremely rare, and carcinoid tumoral elements in renal cell carcinoma have never been reported. This is the first report of a composite renal cell carcinoma containing a clear cell renal cell carcinoma associated with carcinoid tumoral elements, in a patient with synchronous metastatic disease. In the absence of specific radiological and clinical manifestations, typical morphological features as well as an immunostaining profile of neuroendocrine differentiation were identified by microscopy. Secondary nodal and liver localisations were characterised by carcinoid elements only. Despite antiangiogenic therapy, liver metastasis progressed, suggesting that adjuvant therapy cannot be based on the presence of the clear cell renal cell carcinoma component. In this context, extensive tissue sampling is recommended to reveal the endocrine component that is the most aggressive element of such a composite carcinoma.

  13. Toxicity of uranium on renal cells

    Energy Technology Data Exchange (ETDEWEB)

    Thiebault, C.; Carriere, M.; Gouget, B. [CEA Saclay, CNRS, UMR9956, Lab Pierre Sue, F-91191 Gif Sur Yvette, (France)

    2007-07-01

    Kidney and bone are the main retention organs affected by uranium toxicity. Although the clinical effects of uranium poisoning are well known, only few studies dealt with cellular mechanisms of toxicity. The purpose of this study was to investigate the cyto- and genotoxicity of uranium (U) on renal cells. The cell death was also studied in this conditions of exposure. The effects of U were evaluated in acute and chronic exposure. The acute effects were evaluated after 24 h exposure to strong U concentrations (200-700{mu}M). The chronic exposure was observed on renal cells incubated with low U concentrations (0.1-100 {mu}M) until 70 days then with high uranium concentrations (400-500 {mu}M) during 24 h. U induces apoptosis cell death mainly by the intrinsic pathway. The high U concentrations (600-700 {mu}M) lead to necrosis. U induces DNA damages (single, double strand breaks, as well as alkali labile sites) from 300{mu}M. The cytotoxicity and intracellular accumulation of uranium were less important in cells previously exposed to low uranium concentrations when compared to non-exposed cells. In the same time, DNA damage observed after acute exposure of uranium decreased with the increase of chronic uranium concentrations. These results suggest that renal cells became resistant to uranium, probably due to a cellular transformation process. In conclusion, high U concentrations (300-700{mu}M) induce apoptosis cell death and DNA damages. Cells previously exposed to low U concentrations present also DNA damages and a cellular transformation. (authors)

  14. Renal Cell Carcinoma in Tuberous Sclerosis Complex

    Science.gov (United States)

    Yang, Ping; Cornejo, Kristine M.; Sadow, Peter M.; Cheng, Liang; Wang, Mingsheng; Xiao, Yu; Jiang, Zhong; Oliva, Esther; Jozwiak, Sergiusz; Nussbaum, Robert L.; Feldman, Adam S.; Paul, Elahna; Thiele, Elizabeth A.; Yu, Jane J.; Henske, Elizabeth P.; Kwiatkowski, David J.; Young, Robert H.; Wu, Chin-Lee

    2014-01-01

    Renal cell carcinoma (RCC) occurs in 2-4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathological and molecular features, enabling separation of these 46 tumors into three groups. The largest subset of tumors (n=24) had a distinct morphological, immunological and molecular profile, including prominent papillary architecture and uniformly deficient SDHB expression prompting the novel term “TSC-associated papillary RCC.” The second group (n=15) was morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT) while the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated papillary RCCs (PRCC) had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were the International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCC showed strong, diffuse labeling for CA-IX (100%), CK7 (94%), vimentin (88%), CD10 (83%), and were uniformly negative for succinate dehydrogenase subunit B (SDHB), TFE3 and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes which may help to expand the morphologic spectrum of TSC-associated RCC. PMID:24832166

  15. 无血清微载体培养MDCK细胞和甲型流感病毒H1N1的条件优化%Optimizing the serum- free micro- carrier culture condition of MDCK cells and influenza Virus H1N1

    Institute of Scientific and Technical Information of China (English)

    张严予; 马磊; 沈霏; 周文晶; 周玉波; 王微; 姜述德; 李卫东; 廖国阳

    2011-01-01

    The article is about the optimum culture conditions for micro - carrier cultivating MDCK cells and influenza virus H1N1 proliferation in Serum - Free Medium, which is the basement for the cell influenza vaccine in the future.We cultivated MDCK cell in VP - SFM,detected the effect of MDCK cell growth with different concentration of cell inoculation, then cultivated influenza virus H1N1 in MDCK cell and also detected the effect of different pH value,TPCK -Trypsin content,MOI,whether or not adding TPCK -Trypsin after inoculating influenza virus and different virus harvest time.When the cell quantity is 1.0 x 10 mL-1 ,MDCK cell can grow for 5-6 days,which cell status are in good condition.After inoculating influenza virus H1N1 to MDCK cells,when pH value is between 7.2—7.4 ,TPCK - Trypsin content is 1.0 μg/mL, MOI is 1.0, and virus harvest time is 72 h, the hemagglutination titer is up to 512.In the selected suitable conditions, we could use microcarrier culture method for cultivation of MDCK cells and influenza virus H1N1 in Serum -Free Medium on a large scale in the future.%血清微载体培养MDCK细胞,并接种流感病毒H1N1,优化培养条件,为细胞流感疫苗的工艺研发奠定基础.采用不同的细胞接种量在50mL无血清微载体搅拌瓶中培养MDCK细胞,并接种甲型流感病毒H1N1,检测不同pH值和TPCK-胰酶含量的病毒培养液,不同病毒接种量,补加TPCK-胰酶,以及不同收毒时间对血凝效价的影响.以1.0×105 mL-1的MDCK细胞数量接种到无血清微载体上,病毒培养液pH值为7.2~7.4范围内,TPCK-胰酶质量浓度为1.0μg/mL,接种后不补加胰酶,病毒接种量MOI=1.0,并在72 h收获,最高血凝效价达到512.由此获得了在无血清为载体上培养MDCK细胞和甲型流感病毒H1N1的适宜条件.

  16. Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

    Science.gov (United States)

    George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

    2016-01-01

    Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end

  17. Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury

    Directory of Open Access Journals (Sweden)

    Jia Xiaohua

    2012-09-01

    Full Text Available Abstract Background Bone marrow (BM stem cells have been reported to contribute to tissue repair after kidney injury model. However, there is no direct evidence so far that BM cells can trans-differentiate into renal stem cells. Methods To investigate whether BM stem cells contribute to repopulate the renal stem cell pool, we transplanted BM cells from transgenic mice, expressing enhanced green fluorescent protein (EGFP into wild-type irradiated recipients. Following hematological reconstitution and ischemia-reperfusion (I/R, Sca-1 and c-Kit positive renal stem cells in kidney were evaluated by immunostaining and flow cytometry analysis. Moreover, granulocyte colony stimulating factor (G-CSF was administrated to further explore if G-CSF can mobilize BM cells and enhance trans-differentiation efficiency of BM cells into renal stem cells. Results BM-derived cells can contribute to the Sca-1+ or c-Kit+ renal progenitor cells population, although most renal stem cells came from indigenous cells. Furthermore, G-CSF administration nearly doubled the frequency of Sca-1+ BM-derived renal stem cells and increased capillary density of I/R injured kidneys. Conclusions These findings indicate that BM derived stem cells can give rise to cells that share properties of renal resident stem cell. Moreover, G-CSF mobilization can enhance this effect.

  18. CONVENTIONAL RENAL CELL CARCINOMA WITH GRANULOMATOUS REACTION

    Directory of Open Access Journals (Sweden)

    Srinivas

    2014-09-01

    Full Text Available : Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by microscopic aggregation of activated macrophages which often develop epithelioid appearance and multinucleate giant cells. Granulomas are encountered in limited number of infectious and some non-infectious conditions. Granulomas have been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma and Hodgkin’s lymphoma, where they represent T-cell-mediated reaction of the tumor stroma to antigens expressed by the tumor. Granulomatous reaction in association with renal cell carcinoma (RCC is uncommon, with only few published reports in the literature. We describe a case of conventional (clear cell RCC associated with epithelioid cell granulomas within the tumor parenchyma.

  19. Computed tomography of renal cell carcinoma in patients with terminal renal impairment

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiri [Department of Radiology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic)], E-mail: ferda@fnplzen.cz; Hora, Milan [Department of Urology, Charles University Hospital Plzen, Dr. Edvarda Benese 13, CZ-306 40 Plzen (Czech Republic); Hes, Ondrej [Institut of Pathology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Reischig, Tomas [Department of Internal Medicine, Nephrology Unit, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Kreuzberg, Boris; Mirka, Hynek; Ferdova, Eva; Ohlidalova, Kristyna; Baxa, Jan [Department of Radiology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Urge, Tomas [Department of Urology, Charles University Hospital Plzen, Dr. Edvarda Benese 13, CZ-306 40 Plzen (Czech Republic)

    2007-08-15

    Purpose: An increased incidence of renal tumors has been observed in patients with end-stage-renal-disease (ESRD). The very strong association with acquired renal cystic disease (ACRD) and increased incidence of the renal tumors (conventional renal cell carcinoma (CRCC), papillary renal cell carcinoma (PRCC) or papillary renal cell adenoma (PRCA)) was reported. This study discusses the role of computed tomography (CT) in detecting renal tumors in patients with renal impairment: pre-dialysis, those receiving dialysis or with renal allograft transplants. Materials and methods: Ten patients (nine male, one female) with renal cell tumors were enrolled into a retrospective study; two were new dialysis patients, three on long-term dialysis, and five were renal transplant recipients with history of dialysis. All patients underwent helical CT, a total of 11 procedures were performed. Sixteen-row detector system was used five times, and a 64-row detector system for the six examinations. All patients underwent nephrectomy of kidney with suspected tumor, 15 nephrectomies were performed, and 1 kidney was assessed during autopsy. CT findings were compared with macroscopic and microscopic assessments of the kidney specimen in 16 cases. Results: Very advanced renal parenchyma atrophy with small cysts corresponding to ESRD was found in nine patients, chronic pyelonephritis in remained one. A spontaneously ruptured tumor was detected incidentally in one case, patient died 2 years later. In the present study, 6.25% (1/16) were multiple PRCA, 12.5% (2/16) were solitary PRCC, 12.5% tumors (2/16) were solitary conventional renal cell carcinomas (CRCC's), 12.5% tumors (2/16) were multiple conventional renal cell carcinomas (CRCC's), 25% (4/16) were CRCC's combined with multiple papillary renal cell carcinomas with adenomas (PRCC's and PRCA's), and 25% (4/16) of the tumors were multiple PRCC's combined with PRCA's without coexisting CRCC

  20. A case report of renal cell carcinoma in a dog

    Directory of Open Access Journals (Sweden)

    A.-S. Paşca

    2013-10-01

    Full Text Available Mix renal carcinoma was noticed during the necropsic examination of a 14 year old mix breed female. Tumours were bilateral and metastasis was noticed in the spleen and myocard. Histological examination evidenced morphological aspects characteristic to the mixt renal carcinoma. Histological aspects described in this individual characterize renal cell carcinoma, also known as renal adenocarcinoma, hypernephroma or, in older literature, Grawitz tumour.

  1. Intravenous Renal Cell Transplantation for Polycystic Kidney Disease

    Science.gov (United States)

    2014-06-01

    reports 28.2 (per million population) PKD patients on dialysis in 1985, 62.9 in 2000 and 92.5 in 2011. Although these data may reflect better diagnosis ...improves renal function and structure in other models of renal failure: CKD due to cisplatin-mediated injury (4), diabetic nephropathy (Am J Physiol...cells prevents progression of chronic renal failure in rats with ischemic-diabetic nephropathy . Am J Physiol. Renal. 305:F1804- F1812 6. Mason SB

  2. The putative P-gp inhibitor telmisartan does not affect the transcellular permeability and cellular uptake of the calcium channel antagonist verapamil in the P-glycoprotein expressing cell line MDCK II MDR1

    DEFF Research Database (Denmark)

    Saaby, Lasse; Tfelt-Hansen, Peer; Brodin, Birger

    2015-01-01

    Verapamil is used in high doses for the treatment of cluster headache. Verapamil has been described as a P-glycoprotein (P-gp, ABCB1) substrate. We wished to evaluate in vitro whether co administration of a P-gp inhibitor with verapamil could be a feasible strategy for increasing CNS uptake...... of verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR1 monolayers were measured in the absence and presence of the putative P-gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral-to-apical transepithelial efflux across the MDCK II MDR1...

  3. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    Science.gov (United States)

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

  4. Clear cell papillary renal cell carcinoma: micro-RNA expression profiling and comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma.

    Science.gov (United States)

    Munari, Enrico; Marchionni, Luigi; Chitre, Apurva; Hayashi, Masamichi; Martignoni, Guido; Brunelli, Matteo; Gobbo, Stefano; Argani, Pedram; Allaf, Mohamad; Hoque, Mohammad O; Netto, George J

    2014-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. Micro-RNAs (miRNAs) are small noncoding RNAs that play a crucial role in regulating gene expression and are involved in various biological processes, including cancer development. To better understand the biology of this tumor, we aimed to analyze the miRNA expression profile of a set of CCPRCC using microarray and quantitative reverse transcription-polymerase chain reaction. A total of 15 cases diagnosed as CCPRCC were used in this study. Among the most differentially expressed miRNA in CCPRCC, we found miR-210, miR-122, miR-34a, miR-21, miR-34b*, and miR-489 to be up-regulated, whereas miR-4284, miR-1202, miR-135a, miR-1973, and miR-204 were down-regulated compared with normal renal parenchyma. To identify consensus of differentially regulated miRNA between CCPRCC, CCRCC, and PRCC, we additionally determined differential miRNA expression using 2 publically available microarray data sets from the NCBI Gene Expression Omnibus database (GSE41282 and GSE3798). This comparison revealed that the miRNA expression profile of CCPRCC shows some overlapping characteristics between CCRCC and PRCC. Moreover, CCPRCC lacks dysregulation of important miRNAs typically associated with aggressive behavior. In summary, we describe the miRNA expression profile of a relatively infrequent type of renal cancer. Our results may help in understanding the molecular underpinning of this newly recognized entity. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Wnt Signaling in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-06-01

    Full Text Available Renal cell carcinoma (RCC accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers.

  6. Renal cell carcinoma: links and risks

    Directory of Open Access Journals (Sweden)

    Kabaria R

    2016-03-01

    Full Text Available Reena Kabaria, Zachary Klaassen, Martha K Terris Department of Surgery, Section of Urology, Augusta University, Augusta, GA, USA Abstract: This review provides an overview of the incidence of renal cell carcinoma (RCC and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses. The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. Keywords: renal cell carcinoma, risk factors, incidence, smoking, obesity, hypertension

  7. A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    2016-09-15

    Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma

  8. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.

    Directory of Open Access Journals (Sweden)

    Cynthia A Batchelder

    Full Text Available Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease.

  9. Unilateral renal cell carcinoma with coexistent renal disease: a rare cause of end-stage renal disease.

    Science.gov (United States)

    Peces, R; Alvarez-Navascués, R

    2001-02-01

    Renal cell carcinoma (RCC) is a disorder encompassing a wide spectrum of pathological renal lesions. Coexistence of unilateral RCC and associated pathology in the contralateral kidney is an unusual and challenging therapeutic dilemma that can result in renal failure. So far, data on unilateral RCC with chronic renal failure necessitating renal replacement therapy have not been published. The aim of the present study was to evaluate the incidence of end-stage renal disease (ESRD) from unilateral RCC, and to assess the associated pathology and possible pathogenic factors. In 1999, a survey of the 350 patients treated by chronic dialysis in Asturias, Spain, was carried out to identify and collect clinical information on patients with primary unilateral RCC whilst on their renal replacement programme. Seven patients were identified as having ESRD and unilateral RCC, giving an incidence of 2% of patients treated by dialysis. There was a wide spectrum of associated disease and clinical presentation. All patients underwent radical or partial nephrectomy and were free of recurrence 6--64 months after surgery. Six patients were alive and free of malignancy recurrence for 6--30 months after the onset of haemodialysis. ESRD is rare in association with unilateral RCC, but does contribute to significant morbidity. However, the data presented here are encouraging and suggest that cancer-free survival with renal replacement therapy can be achieved in such patients.

  10. Bilateral acrometastasis in a case renal cell carcinoma

    Science.gov (United States)

    Vaishya, Raju; Vijay, Vipul; Vaish, Abhishek

    2014-01-01

    We present a unique case of bilateral skeletal metastasis below the knee in a patient with renal cell carcinoma. In this rarest of rare cases, bony metastases were the first presentation of a primary tumour. Incidentally, the primary tumour (renal cell carcinoma) involved the solitary kidney of the patient and the same patient also had coexisting carcinoma of the prostate. PMID:25368128

  11. Conditional survival predictions after nephrectomy for renal cell carcinoma.

    NARCIS (Netherlands)

    Karakiewicz, P.I.; Suardi, N.; Capitanio, U.; Isbarn, H.; Jeldres, C.; Perrotte, P.; Sun, M.; Ficarra, V.; Zigeuner, R.; Tostain, J.; Mejean, A.; Cindolo, L.; Pantuck, A.J.; Belldegrun, A.S.; Zini, L.; Taille, A. De La; Chautard, D.; Descotes, J.L.; Shariat, S.F.; Valeri, A.; Mulders, P.F.A.; Lang, H.; Lechevallier, E.; Patard, J.J.

    2009-01-01

    PURPOSE: Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. MATERIALS AND METHODS: We studied 3,560 patients with renal cell carcinoma of all stag

  12. A Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sarah Mehrtens

    2016-01-01

    Full Text Available A 49-year-old lady presented with multiple recurring painful lesions over her thighs, arms, and back. Past medical history included a left sided nephrectomy for renal cell carcinoma and a hysterectomy for multiple uterine fibroids (leiomyomas. Histopathological examination revealed changes consistent with pilar leiomyomas. Gene mutation analysis confirmed a diagnosis of hereditary leiomyomatosis and renal cell carcinoma. Hereditary leiomyomatosis and renal cell carcinoma is an uncommon autosomal dominant condition characterised by the concurrent presentation of cutaneous and uterine leiomyomas. Renal cell carcinoma associated with this condition is more aggressive and a significant cause of mortality. Due to this association with potentially fatal renal cell carcinoma we felt that it was important to highlight this case with an update on pathophysiology and management.

  13. Renal Differentiation of Mesenchymal Stem Cells Seeded on Nanofibrous Scaffolds Improved by Human Renal Tubular Cell Lines-Conditioned Medium.

    Science.gov (United States)

    Ardeshirylajimi, Abdolreza; Vakilian, Saeid; Salehi, Mohammad; Mossahebi-Mohammadi, Majid

    Kidney injuries and renal dysfunctions are one of the most important clinical problems, and tissue engineering could be a valuable method for solving it. The objective of this study was to investigate the synergistic effect of renal cell line-conditioned medium and Polycaprolactone (PCL) nanofibers on renal differentiation of human mesenchymal stem cells (MSCs). In the current study, after stem cells isolation and characterization, PCL nanofibrous scaffold was fabricated using electrospinning methods and characterized morphologically, mechanically, and for biocompatibility. The renal differentiation of seeded MSCs on the surface of PCL nanofibers with and without human renal tubular cell lines-conditioned medium was investigated by evaluation of eight important renal-related genes expression by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. Fabricated nanofibrous scaffolds were good in all characterized items. Almost highest expression of all genes was detected in stem cells seeded on PCL under conditioned media in comparison with the stem cells seeded on PCL, tissue culture polystyrene (TCPS) under renal induction medium, and TCPS under conditioned medium. According to the results, PCL nanofibers in contribution with conditioned medium can provide the optimal conditions for renal differentiation of MSCs and could be a promising candidate for renal tissue engineering application.

  14. Current MR imaging of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sae Lin; Sung, Seuk Jae [Dept. of Radiology, Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2016-08-15

    Renal cell carcinoma (RCC) consists of approximately 85-90% of renal masses, and its incidence is increasing due to widespread use of modern imaging modalities such as ultrasonography or computed tomography. Computed tomography has served an important role in the diagnosis and staging of RCC; however, recent advances in magnetic resonance imaging (MRI) techniques have considerably improved our ability to predict tumor biology beyond the morphologic assessment. Multiparametric MRI protocols include standard sequences tailored for the morphologic evaluation and acquisitions that provide information about the tumor microenvironment such as diffusion-weighted imaging and dynamic contrast-enhanced MRI. The role of multiparametric MRI in the evaluation of RCC now extends to preoperative characterization of RCC subtypes, histologic grade, and quantitative assessment of tumor response to targeted therapies in patients with metastatic disease. Herein, the clinical applications and recent advances in MRI applied to RCC are reviewed along with its merits and demerits. We aimed to review MRI techniques and image analysis that can improve the management of patients with RCC. Familiarity with the advanced MRI techniques and various imaging findings of RCC would also facilitate optimal clinical recommendations for patients.

  15. EVALUATION OF RENAL FUNCTION IN PATIENTS WITH RENAL CELL CARCINOMA BEFORE AND AFTER RADICAL NEPHRECTOMY

    Directory of Open Access Journals (Sweden)

    M. I. Kogan

    2011-01-01

    Full Text Available There is an increase in the number of patients with renal cell carcinoma (RCC every year. At the same time radical nephrectomy (RN remains the standard treatment of renal malignancies and the most common surgical procedure for this pathology. A considerable number of patients with kidney cancer have diminished renal function that worsens after removal of functioning kidney tissue together with a tumor. This promotes retained low overall survival rates in patients with RCC, by improving cancer-specific survival. Renal function was studied in 48 patients with RCC prior to and 1 year after RN. In all the patients, glomerular filtration rate (GFR was estimated using the Cockroft-Gault equation with and without protein load. Renal parenchyma volume was calculated by spiral computed tomography. Patients aged over 60 years had decreased baseline renal function as compared to those aged under 60 years (GFR 77.4 versus 103.6 ml/min/1.73 m2. The postoperative reduction in female renal function was more pronounced (GFR, 84.92 versus 92.54 ml/min/1.73 m2. Patients with metastatic RCC had lower baseline renal function and its significant postoperative loss than those with the non-metastatic forms of a tumor. A load test showed a substantially decreased renal reserve in patients with RCC.

  16. ZO-2 silencing induces renal hypertrophy through a cell cycle mechanism and the activation of YAP and the mTOR pathway

    Science.gov (United States)

    Domínguez-Calderón, Alaide; Ávila-Flores, Antonia; Ponce, Arturo; López-Bayghen, Esther; Calderón-Salinas, José-Víctor; Luis Reyes, José; Chávez-Munguía, Bibiana; Segovia, José; Angulo, Carla; Ramírez, Leticia; Gallego-Gutiérrez, Helios; Alarcón, Lourdes; Martín-Tapia, Dolores; Bautista-García, Pablo; González-Mariscal, Lorenza

    2016-01-01

    Renal compensatory hypertrophy (RCH) restores normal kidney function after disease or loss of kidney tissue and is characterized by an increase in organ size due to cell enlargement and not to cell proliferation. In MDCK renal epithelial cells, silencing of the tight junction protein zona occludens 2 (ZO-2 KD) induces cell hypertrophy by two mechanisms: prolonging the time that cells spend at the G1 phase of the cell cycle due to an increase in cyclin D1 level, and augmenting the rate of protein synthesis. The latter is triggered by the nuclear accumulation and increased transcriptional activity of Yes-associated protein (YAP), the main target of the Hippo pathway, which results in decreased expression of phosphatase and tensin homologue. This in turn increased the level of phosphatidylinositol (3,4,5)-triphosphate, which transactivates the Akt/mammalian target of rapamycin pathway, leading to activation of the kinase S6K1 and increased synthesis of proteins and cell size. In agreement, in a rat model of uninephrectomy, RCH is accompanied by decreased expression of ZO-2 and nuclear expression of YAP. Our results reveal a novel role of ZO-2 as a modulator of cell size. PMID:27009203

  17. Are primary renal cell carcinoma and metastases of renal cell carcinoma the same cancer?

    Science.gov (United States)

    Semeniuk-Wojtaś, Aleksandra; Stec, Rafał; Szczylik, Cezary

    2016-05-01

    Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Our understanding of this spread is limited and molecular mechanisms causing particular characteristics of metastasis are still unknown. There is some evidence that primary renal cell carcinoma (RCC) and metastases of RCC exhibit molecular differences that may effect on the biological characteristics of the tumor. Some authors have detected differences in clear cell and nonclear cell component between these 2 groups of tumors. Investigators have also determined that primary RCC and metastases of RCC diverge in their range of renal-specific markers and other protein expression, gene expression pattern, and microRNA expression. There are also certain proteins that are variously expressed in primary RCCs and their metastases and have effect on clinical outcome, e.g., endothelin receptor type B, phos-S6, and CD44. However, further studies are needed on large cohorts of patients to identify differences representing promising targets for prognostic purposes predicting disease-free survival and the metastatic burden of a patient as well as their suitability as potential therapeutic targets. To sum up, in this review we have attempted to summarize studies connected with differences between primary RCC and its metastases and their influence on the biological characteristics of renal cancer.

  18. Fitting the elementary rate constants of the P-gp transporter network in the hMDR1-MDCK confluent cell monolayer using a particle swarm algorithm.

    Directory of Open Access Journals (Sweden)

    Deep Agnani

    Full Text Available P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the

  19. Research on Multiplication of H5N1 Subtype Avian Influenza Virus in MDCK Cell Culture System%H5N1亚型禽流感病毒在MDCK细胞中增殖条件的研究

    Institute of Scientific and Technical Information of China (English)

    孙德君; 梁婉楠; 丁国杰; 刘鑫莹; 袁明霞; 闫妍

    2014-01-01

    目的:探索H5N1亚型禽流感病毒在MDCK中增殖规律,确定最佳增殖条件。方法将H5N1亚型禽流感病毒接种到6孔板培养的MDCK细胞进行增殖试验,检测不同病毒感染量、不同浓度TPCK-胰酶,接毒后不同时间病毒的HA滴度。根据确定的最佳增殖条件将病毒接种到微载体培养的MDCK细胞中进行大规模增殖。结果:最佳病毒增殖条件接毒量MOI为5×10-4、TPCK-胰酶浓度为4μg/mL,在5 L生物反应器中重复验证,获得稳定的试验结果,病毒血凝价最高为8 log2。结论:本研究为禽流感疫苗的生物反应器规模化生产奠定了基础。%To explore the regularity for the multiplication of avian influenza virus subtype H5N1 in MDCK cell culture system and determine the optimal proliferation conditions. H5N1 subtype of avian influenza virus was in-oculated into the MDCK cell growing on 6 well plate, and the HA titers of virus at different time were detected in the conditions of different infectious doses, and different concentrations of TPCK-trypsin. The optimal conditions were determined. Then the H5N1 subtype avian influenza virus was grown in microcarrier-based MDCK cell. It was demonstrated that high virus yield with a hemagglutination unit of 8 log2 (1:256) could be obtained under the optimal conditions of multiplication. The result indicated the H5N1 subtype avian influenza virus could be pro-duced in microcarrier-based MDCK cell in a large-scale culture system with a high virus yield and demonstrates the feasibility of the development of mammalian cell-based in influenza vaccine in microcarrier culture systems.

  20. Unilateral Blepharoptosis From Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Federico Greco

    2016-12-01

    Full Text Available Blepharoptosis is the drooping or inferior displacement of the upper eyelid. Blepharoptosis can be either congenital or acquired. Tumour metastasis is one of the acquired causes of blepharoptosis. The lungs, locoregional lymph nodes, bone and liver are the usual sites of metastases of renal cell carcinoma (RCC; however, unusual locations of RCC have also been reported. Herein, we describe a case of a 47-year-old man with unilateral ptosis and blurred vision due to metastatic RCC. We describe the different causes of blepharopstosis, the path that led to the diagnosis, and how RCC can metastasize to unusual anatomical regions such as the orbit. Symptoms such as exophthalmos, lid edema, diplopia, ptosis, cranial nerve paralysis or blurred vision may mime a benign disease; however, they could also be the symptoms of a systemic malignancy.

  1. Metabolic alterations in renal cell carcinoma.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Piva, Francesco; Modena, Alessandra; Bimbatti, Davide; Fantinel, Emanuela; Santini, Daniele; Cheng, Liang; Cascinu, Stefano; Montironi, Rodolfo; Tortora, Giampaolo

    2015-11-01

    Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies.

  2. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-01-01

    Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC) and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested. PMID:21577373

  3. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tarun Rustagi

    2011-04-01

    Full Text Available Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested.

  4. Computed tomography in metastatic renal cell carcinoma.

    Science.gov (United States)

    Griffin, Nyree; Grant, Lee Alexander; Bharwani, Nishat; Sohaib, S Aslam

    2009-08-01

    Recent developments in chemotherapy have resulted in several new drug treatments for metastatic renal cell carcinoma (RCC). These therapies have shown improved progression-free survival and are applicable to many more patients than the conventional cytokine-based treatments for metastatic RCC. Consequently imaging is playing a greater part in the management of such patients. Computed tomography (CT) remains the primary imaging modality with other imaging modalities playing a supplementary role. CT is used in the diagnosis and staging of metastatic RCC. It is used in the follow-up of patients after nephrectomy, in assessing the extent of metastatic disease, and in evaluating response to treatment. This review looks at the role of CT in patients with metastatic RCC and describes the appearances of metastatic RCC before and following systemic therapy.

  5. Duodenal bleeding from metastatic renal cell carcinoma.

    Science.gov (United States)

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-04-20

    Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC) and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested.

  6. Renal cell carcinoma: links and risks

    Science.gov (United States)

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  7. Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure.

    Science.gov (United States)

    Humes, H David; Weitzel, William F; Bartlett, Robert H; Swaniker, Fresca C; Paganini, Emil P

    2003-01-01

    Renal cell therapy in conjunction with continuous hemofiltration techniques may provide important cellular metabolic activities to patients with acute renal failure (ARF) and may thereby change the natural history of this disorder. The development of a tissue-engineered bioartificial kidney consisting of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10(9) human renal proximal tubule cells provides an opportunity to evaluate this form of therapy in patients with ARF in the intensive care unit. Nine patients with ARF and multi-organ systems failure (MOSF) have been treated so far with a tissue-engineered kidney in an FDA-approved Phase I/II clinical study currently underway. Acute physiologic parameters and serum cytokine levels were assessed before, during and after treatment with a bioartificial kidney. Use of the RAD in this clinical setting demonstrates maintenance of cell viability and functionality. Cardiovascular stability appears to be maintained during RAD treatment. Human tubule cells in the RAD demonstrated differentiated metabolic and endocrinologic activity. Acute physiologic and plasma cytokine data demonstrate that renal cell therapy is associated with rapid and variable responses in patients with ARF and MOSF. The initial clinical experience with the bioartificial kidney and the RAD suggests that renal tubule cell therapy may provide a dynamic and individualized treatment program as assessed by acute physiologic and biochemical indices. Copyright 2003 S. Karger AG, Basel

  8. Cellular adaptive response of distal renal tubular cells to high-oxalate environment highlights surface alpha-enolase as the enhancer of calcium oxalate monohydrate crystal adhesion.

    Science.gov (United States)

    Kanlaya, Rattiyaporn; Fong-Ngern, Kedsarin; Thongboonkerd, Visith

    2013-03-27

    Hyperoxaluria is one of etiologic factors of calcium oxalate kidney stone disease. However, response of renal tubular cells to high-oxalate environment remained largely unknown. We applied a gel-based proteomics approach to characterize changes in cellular proteome of MDCK cells induced by 10mM sodium oxalate. A total of 14 proteins were detected as differentially expressed proteins. The oxalate-induced up-regulation of alpha-enolase in whole cell lysate was confirmed by 2-D Western blot analysis. Interaction network analysis revealed that cellular adaptive response under high-oxalate condition involved stress response, energy production, metabolism and transcriptional regulation. Down-regulation of RhoA, which was predicted to be associated with the identified proteins, was confirmed by immunoblotting. In addition, the up-regulation of alpha-enolase on apical surface of renal tubular epithelial cells was also confirmed by immunoblotting of the isolated apical membranes and immunofluorescence study. Interestingly, blockage of alpha-enolase expressed on the cell surface by antibody neutralization significantly reduced the number of calcium oxalate monohydrate (COM) crystals adhered on the cells. These results strongly suggest that surface alpha-enolase plays an important role as the enhancer of COM crystal binding. The increase of alpha-enolase expressed on the cell surface may aggravate kidney stone formation in patients with hyperoxaluria. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Assay development of inducible human renal phosphate transporter Npt2A (SLC34A1) in Flp-In-Trex-HEK293 cells.

    Science.gov (United States)

    Wu, Hongzhong; Mao, Chonghong; Duenstl, Georg; Su, Wan; Qian, Su

    2013-12-01

    Hyperphosphatemia is associated with severe decline of renal function in chronic kidney disease and elevates cardiovascular mortality. Type II sodium dependent phosphate transporter 2A (Npt2A) plays a major role in renal phosphate reabsorption and could be explored as a target for anti-hyperphosphatemia therapy. Human Npt2A transporter activity was examined upon transfection into CHO, MDCK, HEK293, Flp-In-CHO and Flp-In-HEK293 cells. Only kidney-derived cells expressed functional Npt2A. HEK293 and Flp-In-HEK293 cell lines stably transfected with hNpt2A could be selected, but these cells were inactive in phosphate transport. This suggests that high-level, constitutive Npt2A expression has deleterious effects on the cell. By using the conditional promoter in the Flp-In-Trex vector, functional expression of Npt2A was achieved by doxycycline induction in HEK293 cells. The EGFP tagged and non-tagged, inducible stable hNpt2A-HEK293 cell lines afforded development of a robust phosphate uptake assay mediated by hNpt2A, which can be used to screen hNpt2A inhibitors and inducers of hNpt2A expression. Using this assay, the small molecule LC-1 was identified as a potent inhibitor of hNpt2A, suggesting that it is feasible to develop potent specific hNpt2A inhibitors to control phosphate overloading for hyperphosphatemia therapy.

  10. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  11. Renal stem cells and their implications for kidney cancer.

    Science.gov (United States)

    Axelson, Håkan; Johansson, Martin E

    2013-02-01

    The renal cell carcinomas (RCC) denote a diverse set of neoplasias with unique genetic and histological features. The RCCs emanate from the renal tubule, a highly heterogeneous epithelial structure, and depending on which cell is malignified the resulting cancer displays unique characteristics. Notwithstanding this, the cells of origin for the RCC forms are far from established, and only inferred by the accumulated weight of marker similarities, not always providing an unequivocal picture. The tubular epithelium is normally mitotically quiescent, but demonstrates a considerable regenerative capacity upon renal injury. Recently the hypothesis that regeneration is driven by adult stem cells has been added experimental support, providing further complexity to the issue of renal carcinogenesis. Whether these cells are linked to RCC is an open question. In the present review we therefore present the prevailing theories regarding kidney regeneration, since a better understanding of this process might be of relevance when considering the different malignancies that arise from kidney epithelium. Our own results show that papillary renal cell carcinoma displays considerable similarities to proximal tubular progenitor cells and we suggest that this tumor form may develop in a multi-step fashion via benign renal adenomas. The putative connection between renal stem cells and carcinomas is, however, not clarified, since the current understanding of the renal stem cell system is not complete. It is clear that the efforts to isolate and characterize renal progenitor/stem cells suffer from numerous technical limitations and that it remains likely that the kidney harbors different stem cell pools with a restricted differentiation potential.

  12. Isolated renal metastasis from squamous cell lung cancer

    Directory of Open Access Journals (Sweden)

    Cai Jun

    2013-01-01

    Full Text Available Abstract Renal metastasis from non-small cell lung cancer is rather uncommon. The mechanism underlying the occurrence of metastasis in this site is still not well understood. We report a case of a 53-year-old Chinese woman who had moderately differentiated squamous cell carcinoma of the lung. After a ten months post-surgery interval of disease free survival, computed tomography (CT scan found that left renal parenchymal was occupied by a mass, confirmed by kidney biopsy to be a metastasis from squamous cell lung carcinoma. Based on this case, we are warned to be cautious in diagnosis and treatment when renal lesion are detected.

  13. A patient with Multiple myeloma and Renal cell carcinoma.

    Science.gov (United States)

    Shahi, Farhad; Ghalamkari, Marziye; Mirzania, Mehrzad; Khatuni, Mahdi

    2016-01-01

    The coexistence of two malignancies is rarely seen. A little association between hematologic malignancies especially multiple myeloma and renal cell carcinoma has been reported in the recent past. Several case series revealed a bidirectional association between these two malignancies which may be due to the common risk factors, similar cytokine growth requirements and clinical presentation. Here, we aim to describe a patient who had multiple myeloma and in his work up renal cell carcinoma was found out incidentally. We would like to create awareness among clinicians for the coincidence of Renal cell carcinoma and Multiple myeloma.

  14. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F;

    2015-01-01

    BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg...... patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.)....

  15. An Immune Atlas of Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Chevrier, Stéphane; Levine, Jacob Harrison; Zanotelli, Vito Riccardo Tomaso; Silina, Karina; Schulz, Daniel; Bacac, Marina; Ries, Carola Hermine; Ailles, Laurie; Jewett, Michael Alexander Spencer; Moch, Holger; van den Broek, Maries; Beisel, Christian; Stadler, Michael Beda; Gedye, Craig; Reis, Bernhard; Pe'er, Dana; Bodenmiller, Bernd

    2017-05-04

    Immune cells in the tumor microenvironment modulate cancer progression and are attractive therapeutic targets. Macrophages and T cells are key components of the microenvironment, yet their phenotypes and relationships in this ecosystem and to clinical outcomes are ill defined. We used mass cytometry with extensive antibody panels to perform in-depth immune profiling of samples from 73 clear cell renal cell carcinoma (ccRCC) patients and five healthy controls. In 3.5 million measured cells, we identified 17 tumor-associated macrophage phenotypes, 22 T cell phenotypes, and a distinct immune composition correlated with progression-free survival, thereby presenting an in-depth human atlas of the immune tumor microenvironment in this disease. This study revealed potential biomarkers and targets for immunotherapy development and validated tools that can be used for immune profiling of other tumor types. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Incidentally detected clear cell renal cell carcinoma with rhabdoid differentiation

    Directory of Open Access Journals (Sweden)

    Venkatesh Krishnamoorthy

    2016-01-01

    Full Text Available Renal cell carcinoma with rhabdoid differentiation (RCC-R has an aggressive biologic behavior and poor prognosis. A recent consensus statement of the International Society of Urological Pathology (ISUP proposed a nucleolar grading system (ISUP grade for RCC to replace Fuhrman system and recommended reporting the presence of rhabdoid differentiation and considering tumors with rhabdoid differentiation to be ISUP Grade 4. We report a case of incidentally detected clear cell RCC-R in a 52-year-old man. This is one of the earliest cases of RCC-R (pT1b detected and first such case from Indian subcontinent.

  17. Incidentally detected clear cell renal cell carcinoma with rhabdoid differentiation.

    Science.gov (United States)

    Krishnamoorthy, Venkatesh; Gowda, Kiran Krishne; Rao, Raman Narayana

    2016-01-01

    Renal cell carcinoma with rhabdoid differentiation (RCC-R) has an aggressive biologic behavior and poor prognosis. A recent consensus statement of the International Society of Urological Pathology (ISUP) proposed a nucleolar grading system (ISUP grade) for RCC to replace Fuhrman system and recommended reporting the presence of rhabdoid differentiation and considering tumors with rhabdoid differentiation to be ISUP Grade 4. We report a case of incidentally detected clear cell RCC-R in a 52-year-old man. This is one of the earliest cases of RCC-R (pT1b) detected and first such case from Indian subcontinent.

  18. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    Science.gov (United States)

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  19. Renal cell carcinoma: complete pathological response in a patient with gastric metastasis of renal cell carcinoma.

    Science.gov (United States)

    García-Campelo, Rosario; Quindós, Maria; Vázquez, Diana Dopico; López, Margarita Reboredo; Carral, Alberto; Calvo, Ovidio Fernández; Soto, José Manuel Rois; Grande, Enrique; Durana, Jesús; Antón-Aparicio, Luis Miguel

    2010-01-01

    A 75-year-old-man, with a 2-month history of abdominal pain, underwent a standard diagnostic workup that included a CT scan that showed a large right renal mass and subcentimeter nodes in the right and left lung lobes. In December 2003, the patient underwent right nephrectomy with adrenalectomy and a diagnosis of renal cell carcinoma (pT3N0M0 stage) was made. No further treatment was proposed and patient was followed up regularly. In October 2006, the annual gastrointestinal endoscopy showed asymptomatic multilobulated and polypoid masses in the gastric fundus and gastric body that corresponded to metastasis of the renal carcinoma that had been resected three years ago. Surgical treatment was refused and oral treatment with sunitinib (50 mg/day consecutively for 4 weeks followed by 2 weeks off) was initiated. Patient completed one cycle and development of acute toxicity (grade 3 asthenia, anorexia and mucositis) led to treatment interruption. After recovering from acute toxicity, the patient was proposed to reinitiate treatment with dose reduction, but he refused any medical treatment. At the follow-up visit, three months later, the gastrointestinal endoscopy showed four unspecific 2 mm nodules without malignant evidence. The whole-body CT did not reveal any other abnormality except for the known lung nodes. PET scan six months after treatment confirmed complete gastric response.

  20. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

    2017-11-01

    Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

  1. Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation.

    Directory of Open Access Journals (Sweden)

    Chaowalit Yuajit

    Full Text Available Cyst enlargement in polycystic kidney disease (PKD involves cAMP-activated proliferation of cyst-lining epithelial cells and transepithelial fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR chloride channel. This study aimed to investigate an inhibitory effect and detailed mechanisms of steviol and its derivatives on cyst growth using a cyst model in Madin-Darby canine kidney (MDCK cells. Among 4 steviol-related compounds tested, steviol was found to be the most potent at inhibiting MDCK cyst growth. Steviol inhibition of cyst growth was dose-dependent; steviol (100 microM reversibly inhibited cyst formation and cyst growth by 72.53.6% and 38.2±8.5%, respectively. Steviol at doses up to 200 microM had no effect on MDCK cell viability, proliferation and apoptosis. However, steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK epithelia, measured with the Ussing chamber technique, in a dose-dependent manner. Prolonged treatment (24 h with steviol (100 microM also strongly inhibited forskolin-stimulated apical chloride current, in part by reducing CFTR protein expression in MDCK cells. Interestingly, proteasome inhibitor, MG-132, abolished the effect of steviol on CFTR protein expression. Immunofluorescence studies demonstrated that prolonged treatment (24 h with steviol (100 microM markedly reduced CFTR expression at the plasma membrane. Taken together, the data suggest that steviol retards MDCK cyst progression in two ways: first by directly inhibiting CFTR chloride channel activity and second by reducing CFTR expression, in part, by promoting proteasomal degradation of CFTR. Steviol and related compounds therefore represent drug candidates for treatment of polycystic kidney disease.

  2. Ipsilateral synchronous renal pelvic transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    韩平; 魏强; 石明; 杨宇如

    2004-01-01

    @@ Reports of multiple synchronous primary renal neoplasms in the literature are rare. Although primary renal tumors of 2 distinctively dissimilar origins have been sporadically described,1-6 to our knowledge there have been no reported cases of triple primary renal neoplasms in the same kidney. Here we report a very rare case of ipsilateral synchronous renal pelvic transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma with marked hydronephrosis and multiple stones in the same kidney.

  3. Needle tract seeding following percutaneous biopsy of renal cell carcinoma.

    Science.gov (United States)

    Chang, Dwayne T S; Sur, Hariom; Lozinskiy, Mikhail; Wallace, David M A

    2015-09-01

    A 66-year-old man underwent computed tomography-guided needle biopsy of a suspicious renal mass. Two months later he underwent partial nephrectomy. Histology revealed a 30-mm clear cell renal cell carcinoma, up to Fuhrman grade 3. An area of the capsule was interrupted, which corresponded to a hemorrhagic area on the cortical surface. Under microscopy, this area showed a tongue of tumor tissue protruding through the renal capsule. A tumor deposit was found in the perinephric fat. These features suggest that tumor seeding may have occurred during the needle biopsy.

  4. Renal cell carcinoma presenting as hemolytic anemia in pregnancy.

    Science.gov (United States)

    Monga, M; Benson, G S; Parisi, V M

    1995-03-01

    A patient presented at 29 weeks' gestation with severe hemolytic anemia. She was subsequently diagnosed as having renal cell carcinoma and had a radical nephrectomy at 31 weeks' gestation, which demonstrated stage I disease. This was followed by a normal vaginal delivery of a healthy infant at term and complete resolution of her anemia. This unusual presentation of renal cell carcinoma in pregnancy is discussed.

  5. Breast Metastasis from Renal Cell Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

    2010-01-15

    Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm.

  6. Role of viruses in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipoor

    2012-01-01

    Full Text Available To determine whether viral infections are related to renal cell carcinoma (RCC, we studied 49 patients with RCC (29 patients were males with age ranging from 30 to 81 years and a mean of 57.5 years; 20 patients were females with age ranging from 36 to 70 years with a mean of 58.4 years and 16 non-neoplastic kidney patients as controls. Tissues specimens from study patients and controls were examined by nested polymerase chain reaction (PCR to determine the presence of DNA of several viruses including human papilloma virus (HPV, Epstein-Barr virus (EBV, and polyoma viruses (BKV and JCV. Our results revealed that 7 of 49 (14.29% RCC tissue specimens had HPV DNA compared with none of 16 non-cancer control subjects. Regarding the HPV types, all the positive results were high-risk HPV types (type 16 in three and 18 in four patients. The present study suggests that HPV infection, especially high-risk types, is associated with RCC. However, more studies are necessary to demonstrate the molecular oncogenic processes involved in this association.

  7. Perfusion computed tomography in renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chandan; J; Das; Usha; Thingujam; Ananya; Panda; Sanjay; Sharma; Arun; Kumar; Gupta

    2015-01-01

    Various imaging modalities are available for the diagnosis, staging and response evaluation of patients with renal cell carcinoma(RCC). While contrast enhanced computed tomography(CT) is used as the standard of imaging for size, morphological evaluation and response assessment in RCC, a new functional imaging technique like perfusion CT(p CT), goes down to the molecular level and provides new perspectives in imaging of RCC. p CT depicts regional tumor perfusion and vascular permeability which are indirect parameters of tumor angiogenesis and thereby provides vital information regarding tumor microenvironment. Also response evaluation using p CT may predate the size criteria used in Response Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier following tissue kinase inhibitors before any actual change in size. This may potentially help in predicting prognosis, better selection of therapy and more accurate and better response evaluation in patients with RCC. This article describes the techniques and role of p CT in staging and response assessment in patients with RCCs.

  8. Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

    OpenAIRE

    Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L.

    2015-01-01

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes ob...

  9. A bioartificial renal tubule device embedding human renal stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Giovanna Sciancalepore

    Full Text Available We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na(+K(+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5% and (13±5%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative "lab-on-a-chip" platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses.

  10. Functional expression of the damage-associated molecular pattern receptor P2X7 on canine kidney epithelial cells.

    Science.gov (United States)

    Jalilian, Iman; Spildrejorde, Mari; Seavers, Aine; Curtis, Belinda L; McArthur, Jason D; Sluyter, Ronald

    2012-12-15

    Epithelial cells are important in inflammation and immunity. In this study, we examined if Madin-Darby canine kidney (MDCK) epithelial cells express functional P2X7 receptors, which bind the damage-associated molecular pattern extracellular adenosine 5'-triphosphate (ATP). Reverse transcription (RT)-PCR and immunoblotting revealed the expression of P2X7 in MDCK cells. A flow cytometric assay demonstrated that ATP or 2'(3')-O-(4-benzoylbenzoyl)ATP induced ethidium(+) uptake into MDCK cells, and that this process was impaired by the P2X7 antagonists KN-62 and A438079. RT-PCR also demonstrated the presence of Toll-like receptor 4, NALP3, caspase-1, interleukin-1β and interleukin-18 in MDCK cells, as well as in positive control LPS-primed canine monocytes. In conclusion, the MDCK epithelial cell line expresses functional P2X7, as well as Toll-like receptor 4 and molecules associated with the NALP3 inflammasome. This cell line may help elucidate the role of these molecules in kidney epithelial cells and renal disorders in dogs and humans.

  11. Renal erythropoietin-producing cells in health and disease

    Directory of Open Access Journals (Sweden)

    Tomokazu eSouma

    2015-06-01

    Full Text Available Erythropoietin (Epo is an indispensable erythropoietic hormone primarily produced from renal Epo-producing cells (REPs. Epo production in REPs is tightly regulated in a hypoxia-inducible manner to maintain tissue oxygen homeostasis. Insufficient Epo production by REPs causes renal anemia and anemia associated with chronic disorders. Recent studies have broadened our understanding of REPs from prototypic hypoxia-responsive cells to dynamic fibrogenic cells. In chronic kidney disease, REPs are the major source of scar-forming myofibroblasts and actively produce fibrogenic molecules, including inflammatory cytokines. Notably, myofibroblast-transformed REPs recover their original physiological properties after resolution of the disease insults, suggesting that renal anemia and fibrosis could be reversible to some extent. Therefore, understanding the plasticity of REPs will lead to the development of novel targeted therapeutics for both renal fibrosis and anemia. This review summarizes the regulatory mechanisms how hypoxia-inducible Epo gene expression is attained in health and disease conditions.

  12. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

  13. Increased Nicotinamide Phosphoribosyltransferase and Cystathionine-β-Synthase in Renal Oncocytomas, Renal Urothelial Carcinoma, and Renal Clear Cell Carcinoma.

    Science.gov (United States)

    Shackelford, Rodney E; Abdulsattar, Jehan; Wei, Eric X; Cotelingam, James; Coppola, Domenico; Herrera, Guillermo A

    2017-07-01

    Renal oncocytomas (ROs), and clear cell (RCC) and urothelial carcinomas (UC), are common renal neoplasms. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of NAD(+) synthesis and its expression is increased in several tumors. Nampt concomitantly regulates hydrogen sulfide (H2S)-synthesizing enzyme levels, including cystathionine-β-synthase (CBS). We used tissue microarrays to examine Nampt and the H2S-synthesizing enzyme CBS protein levels in benign kidney, RCC, UC and ROs. Compared to benign kidney, all three neoplasms showed increased Nampt and CBS protein levels, with the levels increasing in RCC at higher Fuhrman grades. H2S is known to ameliorate chronic renal failure but, as yet, no role for H2S in renal neoplasia has been demonstrated. Here, we showed, for the first time, that Nampt, CBS and, likely, H2S likely play a role in malignant and benign neoplastic renal disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Extracellular signal-regulated kinases 1/2 control claudin-2 expression in Madin-Darby canine kidney strain I and II cells.

    Science.gov (United States)

    Lipschutz, Joshua H; Li, Shixiong; Arisco, Amy; Balkovetz, Daniel F

    2005-02-01

    The tight junction of the epithelial cell determines the characteristics of paracellular permeability across epithelium. Recent work points toward the claudin family of tight junction proteins as leading candidates for the molecular components that regulate paracellular permeability properties in epithelial tissues. Madin-Darby canine kidney (MDCK) strain I and II cells are models for the study of tight junctions and based on transepithelial electrical resistance (TER) contain "tight" and "leaky" tight junctions, respectively. Overexpression studies suggest that tight junction leakiness in these two strains of MDCK cells is conferred by expression of the tight junction protein claudin-2. Extracellular signal-regulated kinase (ERK) 1/2 activation by hepatocyte growth factor treatment of MDCK strain II cells inhibited claudin-2 expression and transiently increased TER. This process was blocked by the ERK 1/2 inhibitor U0126. Transfection of constitutively active mitogen-activated protein kinase/extracellular signal-regulated kinase kinase into MDCK strain II cells also inhibited claudin-2 expression and increased TER. MDCK strain I cells have higher levels of active ERK 1/2 than do MDCK strain II cells. U0126 treatment of MDCK strain I cells decreased active ERK 1/2 levels, induced expression of claudin-2 protein, and decreased TER by approximately 20-fold. U0126 treatment also induced claudin-2 expression and decreased TER in a high resistance mouse cortical collecting duct cell line (94D). These data show for the first time that the ERK 1/2 signaling pathway negatively controls claudin-2 expression in mammalian renal epithelial cells and provide evidence for regulation of tight junction paracellular transport by alterations in claudin composition within tight junction complexes.

  15. Gene expression profile of renal cell carcinoma clear cell type

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall’Oglio

    2010-08-01

    Full Text Available PURPOSE: The determination of prognosis in patients with renal cell carcinoma (RCC is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT. MATERIALS AND METHODS: We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1 low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2 high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3 metastatic RCC-CCT. Normal renal tissue was used as control. RESULTS: After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. CONCLUSION: These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.

  16. PRIMARY SQUAMOUS CELL CARCINOMA OF RENAL PELVIS ASSOCIATED WITH RENAL CALCULUS AND RECURRENT PYONEPHROSIS

    Directory of Open Access Journals (Sweden)

    Hoti Lal

    2015-11-01

    Full Text Available Primary Squamous Cell Carcinoma in the kidney is a rare malignant neoplasm associated with nephrolithiasis, typically monobacterial pyonephrosis and rarely Xanthogranulomatous pyelonephritis. It is an aggressive disease with a poor prognosis mostly due to lack of presenting clinical features like a palpable mass, gross haematuria and pain. We report a case presenting with renal calculus and pyonephrosis managed initially with percutaneous nephrostomy followed by nephrectomy due to complete loss of renal function. Histopathological evaluation revealed poorly differentiated squamous cell carcinoma which is managed by chemotherapy, although initially beneficial, patients later develop disseminated metastatic disease which holds a poor prognosis.

  17. Mechanisms of renal cell repair and regeneration after acute renal failure.

    Science.gov (United States)

    Nony, Paul A; Schnellmann, Rick G

    2003-03-01

    In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is reversed in over half of those who acquire it. Studies using in vivo and in vitro models have demonstrated the importance of proliferation, migration, and repair of physiological functions of injured renal proximal tubular cells (RPTC) in the reversal of ARF. Growth factors have been shown to produce migration and proliferation of injured RPTC, although the specific mechanisms through which growth factors promote renal regeneration in vivo are unclear. Recently, interactions between integrins and extracellular matrix proteins such as collagen IV were shown to promote the repair of physiological functions in injured RPTC. Specifically, collagen IV synthesis and deposition following cellular injury restored integrin polarity and promoted repair of mitochondrial function and active Na(+) transport. Furthermore, exogenous collagen IV, but not collagen I, fibronectin, or laminin, promoted the repair of physiological functions without stimulating proliferation. These findings suggest the importance of establishing and/or maintaining collagen IV-integrin interactions in the stimulation of repair of physiological functions following sublethal cellular injury. Furthermore, the pathway that stimulates repair is distinct from that of proliferation and migration and may be a viable target for pharmacological intervention.

  18. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

    Full Text Available Loren Lipworth1,2, Robert E Tarone1,2, Lars Lund2,3, Joseph K McLaughlin1,21International Epidemiology Institute, Rockville, MD, USA; 2Department of Medicine (JKM, RET and Preventive Medicine (LL, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 3Department of Urology, Viborg Hospital, Viborg, DenmarkAbstract: Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches

  19. The putative P-gp inhibitor telmisartan does not affect the transcellular permeability and cellular uptake of the calcium channel antagonist verapamil in the P-glycoprotein expressing cell line MDCK II MDR1.

    Science.gov (United States)

    Saaby, Lasse; Tfelt-Hansen, Peer; Brodin, Birger

    2015-08-01

    Verapamil is used in high doses for the treatment of cluster headache. Verapamil has been described as a P-glycoprotein (P-gp, ABCB1) substrate. We wished to evaluate in vitro whether co administration of a P-gp inhibitor with verapamil could be a feasible strategy for increasing CNS uptake of verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR1 monolayers were measured in the absence and presence of the putative P-gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral-to-apical transepithelial efflux across the MDCK II MDR1 monolayers with a permeability of 5.7 × 10(-5) cm sec(-1) compared to an apical to basolateral permeability of 1.3 × 10(-5) cm sec(-1). The efflux could be inhibited with the P-gp inhibitor zosuquidar. Zosuquidar (0.4 μmol/L) reduced the efflux ratio (PB-A/PA-B) for verapamil 4.6-1.6. The presence of telmisartan, however, only caused a slight reduction in P-gp-mediated verapamil transport to an efflux ratio of 3.4. Overall, the results of the present in vitro approach indicate, that clinical use of telmisartan as a P-gp inhibitor may not be an effective strategy for increasing brain uptake of verapamil by co-administration with telmisartan.

  20. Pelvic Nephroureterectomy for Renal Cell Carcinoma in an Ectopic Kidney

    Directory of Open Access Journals (Sweden)

    Kevin G. Baldie

    2012-01-01

    Full Text Available We present a case of an ectopic renal tumor in a 61-year-old morbidly obese man with a pelvic kidney found after presenting with hematuria and irritative voiding symptoms. The mass, along with the ectopic kidney and ureter, was radically resected through an open operation that involved removing both them and the renal vessels from the underlying iliac vessels. Pathological analysis demonstrated an 8.3 cm papillary renal cell carcinoma (RCC with oncocytic features, Fuhrman nuclear grade 3, with angiolymphatic invasion and negative margins. The patient has been recurrence-free for over four years since tumor resection.

  1. Clear cell renal cell tumors: Not all that is "clear" is cancer.

    Science.gov (United States)

    Williamson, Sean R; Cheng, Liang

    2016-07-01

    Continued improvement of our understanding of the clinical, histologic, and genetic features of renal cell tumors has progressively evolved renal tumor classification, revealing an expanding array of distinct tumor types with different implications for prognosis, patient counseling, and treatment. Although clear cell renal cell carcinoma is unequivocally the most common adult renal tumor, there is growing evidence that some "clear cell" renal neoplasms, such as exemplified by multilocular cystic clear cell renal neoplasm of low malignant potential (formerly multilocular cystic renal cell carcinoma), do not have the same potential for insidious progression and metastasis, warranting reclassification as low malignant potential tumors or benign neoplasms. Still other novel tumor types such as clear cell papillary renal cell carcinoma have been more recently recognized, which similarly have shown a conspicuous absence of aggressive behavior to date, suggesting that these too may be recategorized as noncancerous or may be premalignant neoplasms. This importance for prognosis is increasingly significant in the modern era, in which renal masses are increasingly found incidentally by imaging techniques at a small tumor size, raising consideration for less aggressive management options guided by renal mass biopsy diagnosis, including imaging surveillance, tumor ablation, or partial nephrectomy.

  2. Gonadal vein tumor thrombosis due to renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hamidreza Haghighatkhah

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC

  3. Gonadal vein tumor thrombosis due to renal cell carcinoma.

    Science.gov (United States)

    Haghighatkhah, Hamidreza; Karimi, Mohammad Ali; Taheri, Morteza Sanei

    2015-01-01

    Renal cell carcinoma (RCC) had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC.

  4. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study.

    Science.gov (United States)

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-05-01

    We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors.

  5. An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Hakimi, A Ari; Reznik, Ed; Lee, Chung-Han; Creighton, Chad J; Brannon, A Rose; Luna, Augustin; Aksoy, B Arman; Liu, Eric Minwei; Shen, Ronglai; Lee, William; Chen, Yang; Stirdivant, Steve M; Russo, Paul; Chen, Ying Bei; Tickoo, Satish K; Reuter, Victor E; Cheng, Emily H; Sander, Chris; Hsieh, James J

    2016-01-11

    Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Using Molecular Biology to Develop Drugs for Renal Cell Carcinoma

    Science.gov (United States)

    Cowey, C. Lance; Rathmell, W. Kimryn

    2010-01-01

    Background Renal cell carcinoma is a disease marked by a unique biology which has governed it’s long history of poor response to conventional cancer treatments. The discovery of the signaling pathway activated as a result of inappropriate constitutive activation of the hypoxia inducible factors (HIF), transcription factors physiologically and transiently stabilized in response to low oxygen, has provided a primary opportunity to devise treatment strategies to target this oncogenic pathway. Objective A review of the molecular pathogenesis of renal cell cancer as well as molecularly targeted therapies, both those currently available and those in development, will be provided. In addition, trials involving combination or sequential targeted therapy are discussed. Methods A detailed review of the literature describing the molecular biology of renal cell cancer and novel therapies was performed and summarized. Results/Conclusion Therapeutics targeting angiogenesis have provided the first class of agents which provide clinical benefit in a large majority of patients and heralded renal cell carcinoma as a solid tumor paradigm for the development of novel therapeutics. Multiple strategies targeting this pathway and now other identified pathways in renal cell carcinoma provide numerous potential opportunities to make major improvements in treating this historically devastating cancer. PMID:20648240

  7. Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir.

    Science.gov (United States)

    Yang, Xi; Ma, Zhiyuan; Zhou, Sisi; Weng, Yayun; Lei, Hongmei; Zeng, Su; Li, Liping; Jiang, Huidi

    2016-10-01

    Entecavir (ETV) is a first-line antiviral agent for the treatment of chronic hepatitis B virus infection. Renal excretion is the major elimination path of ETV, in which tubular secretion plays the key role. However, the secretion mechanism has not been clarified. We speculated that renal transporters mediated the secretion of ETV. Therefore, the aim of our study was to elucidate which transporters contribute to the renal disposition of ETV. Our results revealed that ETV (50 μM) remarkably reduced the accumulation of probe substrates in MDCK cells stably expressing human multidrug and toxin efflux extrusion proteins (hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation transporters (hOCTNs) and increased the substrate accumulation in cells transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the above-described transporters. In transwell studies, the transport of ETV in MDCK-hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and the cellular accumulation of ETV in cells expressing hMATE1 was dramatically lower than that of the mock-treated cells. The accumulation of ETV in mouse primary renal tubular cells was obviously affected by inhibitors of organic anion transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs, MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and reabsorption. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Antagonistic Regulation of Parvalbumin Expression and Mitochondrial Calcium Handling Capacity in Renal Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Thomas Henzi

    Full Text Available Parvalbumin (PV is a cytosolic Ca2+-binding protein acting as a slow-onset Ca2+ buffer modulating the shape of Ca2+ transients in fast-twitch muscles and a subpopulation of neurons. PV is also expressed in non-excitable cells including distal convoluted tubule (DCT cells of the kidney, where it might act as an intracellular Ca2+ shuttle facilitating transcellular Ca2+ resorption. In excitable cells, upregulation of mitochondria in "PV-ergic" cells in PV-/- mice appears to be a general hallmark, evidenced in fast-twitch muscles and cerebellar Purkinje cells. Using Gene Chip Arrays and qRT-PCR, we identified differentially expressed genes in the DCT of PV-/- mice. With a focus on genes implicated in mitochondrial Ca2+ transport and membrane potential, uncoupling protein 2 (Ucp2, mitocalcin (Efhd1, mitochondrial calcium uptake 1 (Micu1, mitochondrial calcium uniporter (Mcu, mitochondrial calcium uniporter regulator 1 (Mcur1, cytochrome c oxidase subunit 1 (COX1, and ATP synthase subunit β (Atp5b were found to be up-upregulated. At the protein level, COX1 was increased by 31 ± 7%, while ATP-synthase subunit β was unchanged. This suggested that these mitochondria were better suited to uphold the electrochemical potential across the mitochondrial membrane, necessary for mitochondrial Ca2+ uptake. Ectopic expression of PV in PV-negative Madin-Darby canine kidney (MDCK cells decreased COX1 and concomitantly mitochondrial volume, while ATP synthase subunit β levels remained unaffected. Suppression of PV by shRNA in PV-expressing MDCK cells led subsequently to an increase in COX1 expression. The collapsing of the mitochondrial membrane potential by the uncoupler CCCP occurred at lower concentrations in PV-expressing MDCK cells than in control cells. In support, a reduction of the relative mitochondrial mass was observed in PV-expressing MDCK cells. Deregulation of the cytoplasmic Ca2+ buffer PV in kidney cells was counterbalanced in vivo and in vitro

  9. [A case of papillary renal cell carcinoma mimicking a hemorrhagic renal cyst].

    Science.gov (United States)

    Yamamuro, Taku; Mitsuzuka, Koji; Sato, Masahiko; Izumi, Hideaki; Kawamorita, Naoki; Saito, Hideo; Kaiho, Yasuhiro; Ito, Akihiro; Nakagawa, Haruo; Arai, Yoichi

    2012-12-01

    A right renal cyst was found in a 69-year-old man with stage IV chronic kidney disease on abdominal ultrasonography performed to investigate a right upper abdominal swelling. Aspiration cytology of the cyst revealed no malignancy, but malignancy could not be ruled out on magnetic resonance imaging because of the cyst's wall thickness and heterogeneous contents. At one-year of follow-up, emergent abdominal surgery was performed due to incidental perforation of ascending colon diverticulitis. At that time, cystic fenestration was performed because the large renal cyst obstructed the operative procedure. Pathological examination showed type-1 papillary renal cell carcinoma, and radical nephrectomy was performed after the patient's general condition improved. Hemodialysis was started after the operation, and there has been no disease recurrence for two years.

  10. Acanthosis Nigricans associated with clear-cell renal cell carcinoma

    Science.gov (United States)

    Narvaez, Margarita Rosa Aveiga; Reis, Paola Vasconcellos Soares; Gomes, Augusto Cesar Marins; Paraskevopoulos, Daniela Kallíope de Sá; Santana, Frederico; Fugita, Oscar Eduardo Hidetoshi

    2016-01-01

    Acanthosis nigricans (AN), an entity recognized since the 19th century, is a dermatopathy associated with insulin-resistant conditions, endocrinopathies, drugs, chromosome abnormalities and neoplasia. The latter, also known as malignant AN, is mostly related to abdominal neoplasms. Malignant AN occurs frequently among elderly patients. In these cases, the onset is subtle, and spreading involves the flexural regions of the body, particularly the axillae, palms, soles, and mucosa. Gastric adenocarcinoma is the most frequent associated neoplasia, but many others have been reported. Renal cell carcinoma (RCC), although already reported, is rarely associated with malignant AN. The authors report the case of a woman who was being treated for depression but presented a long-standing and marked weight loss, followed by darkening of the neck and the axillary regions. Physical examination disclosed a tumoral mass in the left flank and symmetrical, pigmented, velvety, verrucous plaques on both axillae, which is classical for AN. The diagnostic work-up disclosed a huge renal mass, which was resected and further diagnosed as a RCC. The post-operative period was uneventful and the skin alteration was evanescent at the first follow-up consultation. The authors call attention to the association of AN with RCC. PMID:27284539

  11. Unclassified renal cell carcinoma: an analysis of 85 cases.

    NARCIS (Netherlands)

    Karakiewicz, P.I.; Hutterer, G.C.; Trinh, Q.D.; Pantuck, A.J.; Klatte, T.; Lam, J.S.; Guille, F.; Taille, A. De La; Novara, G.; Tostain, J.; Cindolo, L.; Ficarra, V.; Schips, L.; Zigeuner, R.; Mulders, P.F.A.; Chautard, D.; Lechevallier, E.; Valeri, A.; Descotes, J.L.; Lang, H.; Soulie, M.; Ferriere, J.M.; Pfister, C.; Mejean, A.; Belldegrun, A.S.; Patard, J.J.

    2007-01-01

    OBJECTIVES: To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype. PATIENTS AND METHODS: Eighty-five patients with URCC and 4322 with CRCC were identified w

  12. Pilot study of transcatheter arterial ethanol embolization under closed renal circuit for large renal cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Satoru; Tajima, Hiroyuki; Onozawa, Shiro; Kumita, Shinichiro [Nippon Medical School, Department of Radiology/Center for Advanced Medical Technology, Tokyo (Japan); Kondo, Yukihiro [Nippon Medical School, Department of Urology, Tokyo (Japan); Nomura, Kazuhiro [Tokyo Labor-Welfare Hospital, Tokyo (Japan)

    2008-07-15

    The safety of a new technique, designated ''transcatheter arterial embolization (TAE) with aspiration via a balloon-occluded renal drainage vein'' (TAE-ABOD), for the management of large renal cell carcinomas (RCCs). The subjects were 25 patients with RCC who underwent a total of 27 sessions of TAE-ABOD. This TAE-ABOD technique incorporates two procedures: balloon occlusion of renal drainage vein and infusion of absolute ethanol into the tumor-feeding arteries during aspiration of blood via a balloon catheter, thereby reducing leakage of absolute ethanol into the systemic circulation. Our primary endpoint was to establish a safe regimen for high-dose ethanol injection therapy, and our secondary endpoint was to assess global survival of the patients. The administered dose of ethanol ranged from 0.2 to 0.5 ml/kg [median: 0.34 (SD: 0.10) ml/kg], increased in a stepwise manner. The systemic ethanol concentration was measurable in 14 patients, and was less than 0.1 mg/ml in 12 and from 0.1 to less than 0.2 mg/ml in two. There were no major complications such as renal failure or renal abscess. TAE-ABOD can safely deliver a high dose of absolute ethanol for the treatment of large RCCs. (orig.)

  13. Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Cherry, E-mail: cherrykim0505@gmail.com; Choi, Hyuck Jae, E-mail: choihj@amc.seoul.kr; Cho, Kyoung-Sik, E-mail: kscho@amc.seoul.kr

    2014-06-15

    Objective: Although renal sinus fat invasion has prognostic significance in patients with renal cell carcinomas (RCCs), there are no previous studies about the value of multidetector computed tomography (MDCT) about this issue in the current literature. Materials and methods: A total of 863 consecutive patients (renal sinus fat invasion in 110 patients (12.7%)) from single institutions with surgically-confirmed renal cell carcinoma who underwent MDCT between 2010 and 2012 were included in this study. The area under the curves (AUCs) of the receiver operating characteristic (ROC) analysis was used to compare diagnostic performance. Reference standard was pathologic examination. Weighted κ statistics were used to measure the level of interobserver agreement. Multivariate logistic regression model was used to find the predictors for renal sinus fat invasion. Image analysis was first performed with axial-only CT images. A second analysis was then performed with both axial and coronal CT images. A qualitative analysis was then conducted by two reviewers who reached consensus regarding tumor size, decreased perfusion, tumor margin, vessel displacement, and lymph node metastasis. The reference standard was pathologic evaluation. Results: The AUCs of the ROC analysis were 0.881 and 0.922 for axial-only images and 0.889 and 0.902 for combined images in both readers. The AUC of tumor size was 0.884, a similar value to that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or nodular type of fat infiltration, and an irregular tumor margin were independent predicting factors for perinephric fat invasion. Conclusion: MDCT shows relatively high diagnostic performance in detecting perinephric fat invasion of RCC but suffers from a relatively low PPV related to low prevalence of renal sinus fat invasion. Applying tumor size alone we could get similar diagnostic performance to those of radiologists. Tumor size, fat infiltration with a nodular appearance, and

  14. Basosquamous Cell Carcinoma Developing from a Renal Transplantation Recipient

    Directory of Open Access Journals (Sweden)

    Akira Tsukada

    2012-10-01

    Full Text Available We describe a case of basosquamous cell carcinoma arising from a 52-year-old Japanese renal transplantation recipient (RTR. In the present case, we investigated the immunohistochemical profiles of tumor-infiltrating lymphocytes, focusing on cytotoxic granules, granulysin-bearing cells and immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages. Our present study suggests some of the possible mechanisms for the carcinogenesis of cutaneous malignancy in RTRs.

  15. Mesenchymal stem cells and chronic renal artery stenosis.

    Science.gov (United States)

    Oliveira-Sales, Elizabeth B; Boim, Mirian A

    2016-01-01

    Renal artery stenosis is the main cause of renovascular hypertension and results in ischemic nephropathy characterized by inflammation, oxidative stress, microvascular loss, and fibrosis with consequent functional failure. Considering the limited number of strategies that effectively control renovascular hypertension and restore renal function, we propose that cell therapy may be a promising option based on the regenerative and immunosuppressive properties of stem cells. This review addresses the effects of mesenchymal stem cells (MSC) in an experimental animal model of renovascular hypertension known as 2 kidney-1 clip (2K-1C). Significant benefits of MSC treatment have been observed on blood pressure and renal structure of the stenotic kidney. The mechanisms involved are discussed.

  16. Sarcomatoid renal cell carcinoma in a binturong (Arctictis binturong).

    Science.gov (United States)

    Childs-Sanford, Sara E; Peters, Rachel M; Morrisey, James K; Alcaraz, Ana

    2005-06-01

    An adult, female binturong (Arctictis binturong) was examined due to lethargy, inappetence, and an abdominal mass. Diagnostic investigations, including radiographs, abdominal ultrasound, clinical laboratory findings, and a fine-needle aspirate of the mass, were suggestive of a sarcoma with metastasis. Necropsy and histopathologic findings confirmed a widely disseminated sarcomatoid variant of a renal cell carcinoma, likely originating in the left kidney, with metastasis to the right kidney, spleen, pancreas, liver, mesenteric lymph nodes, and lungs. This is the first report of this neoplasm in a binturong and only the second report in the veterinary literature. Sarcomatoid renal cell carcinoma is a rare histologic variant of renal cell carcinoma that is aggressive, commonly metastatic, and associated with a very poor prognosis in humans. Accurate antemortem diagnosis of this tumor may be complicated by its biphasic morphology, which may resemble carcinoma or sarcoma (or both), often necessitating the use of immunohistochemical techniques.

  17. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Rombo, Roman

    2016-04-01

    Full Text Available We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selectiveanti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

  18. Renal stem cell reprogramming: Prospects in regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    Elvin; E; Morales; Rebecca; A; Wingert

    2014-01-01

    Stem cell therapy is a promising future enterprise for renal replacement in patients with acute and chronic kidney disease, conditions which affect millions worldwide and currently require patients to undergo lifelong medical treatments through dialysis and/or organ transplant. Reprogramming differentiated renal cells harvested from the patient back into a pluripotent state would decrease the risk of tissue rejection and provide a virtually unlimited supply of cells for regenerative medicine treatments, making it an exciting area of current research in nephrology. Among the major hurdles that need to be overcome before stem cell therapy for the kidney can be applied in a clinical setting are ensuring the fidelity and relative safety of the reprogrammed cells, as well as achieving feasible efficiency in the reprogramming processes that are utilized. Further, improved knowledge about the genetic control of renal lineage development is vital to identifying predictable and efficient reprogramming approaches, such as the expression of key modulators or the regulation of geneactivity through small molecule mimetics. Here, we discuss several recent advances in induced pluripotent stem cell technologies. We also explore strategies that have been successful in renal progenitor generation, and explore what these methods might mean for the development of cell-based regenerative therapies for kidney disease.

  19. Trigeminal perineural spread of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hornik, Alejandro; Rosenblum, Jordan; Biller, Jose [Stritch School of Medicine, Loyola University Medical Center, Chicago (United States)

    2012-07-01

    A 55-year-old man had a five-day history of 'pins and needles' sensation on the left chin. Examination showed decreased pinprick sensation on the territory of the left mandibular branch of the trigeminal nerve. Brain magnetic resonance imaging (MRI) with gadolinium showed enhancement involving the left mandibular branch. Computed tomography (CT) of the chest, abdomen, and pelvis showed a left kidney mass diagnosed as renal carcinoma following nephrectomy. The 'numb-chin' syndrome heralds or accompanies systemic malignancies. Trigeminal perineural spread has been well-documented in head and neck neoplasms, however, to our knowledge, it has not been reported in renal neoplasms. (author)

  20. Percutaneous and laparoscopic assisted cryoablation of small renal cell carcinomas

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Borre, Michael;

    Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made....... Of the 10 patients with residual tumor, 8 patients were reablated and 2 patients were referred to oncological treatment. Cancer specific survival was 100%. Overall survival was 91%. Complications: 8 pt. had minor bleeding in relation to cryoneedle removal, requiring Tachosil®. 1 pt. had subcutaneous...

  1. A Case of Renal Cell Carcinoma Associated with Paraganglioma

    OpenAIRE

    住吉, 崇幸; 清水, 洋祐; 井上, 貴博; 大久保, 和俊; 渡部, 淳; 神波, 大己; 吉村, 耕治; 兼松, 明弘; 中村, 英二郎; 西山, 博之; 賀本, 敏行; 住吉, 真治; 小川, 修

    2011-01-01

    A 64-year-old man was referred to our hospital for the treatment of left renal cell carcinoma associated with a tumor located on the back of the inferior vena cava. At first the tumor located on the back of the inferior vena cava was suspected to be lymphnode metastasis of renal cell carcinoma. A more detailed examination at our hospital revealed elevation of vanillylmandelic acid in urine and 131Imetaiodobenzylguanidine uptake in the tumor. We diagnosed the tumor as paraganglioma and operate...

  2. Effect of renal and non-renal ischemia/reperfusion on cell-mediated immunity in organs and plasma

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Dagnæs-Hansen, Frederik; Toft, Palle

    2010-01-01

    study, 80 mice were divided into four groups. The following surgeries were performed on the groups compared: bilateral renal I/R by clamping, unilateral renal ischemia, anesthesia only, and unilateral hind leg I/R. Half of the animals were killed after 2 h and the other half after 24 h. To assess...... following renal I/R. All kinds of I/R induced an upregulation of the adhesion molecule CD 11b and a downregulation of MHC II. Renal and non-renal I/R induced neutrophil infiltration in distant organs. Renal I/R does not induce a larger cell-mediated inflammatory response in blood and organs than non-renal I/R....

  3. Renal fibroblast-like cells in Goodpasture syndrome rats.

    Science.gov (United States)

    Okada, H; Inoue, T; Kanno, Y; Kobayashi, T; Ban, S; Kalluri, R; Suzuki, H

    2001-08-01

    The extent of renal fibrosis is the best predictor for functional outcomes in a variety of progressive renal diseases. Interstitial fibroblast-like cells (FbLCs) are presumably involved in the fibrotic process. However, such FbLCs have never been well characterized in the kidney. We characterized renal FbLCs in the nephritic kidney (in which the number of FbLCs and extracellular matrix accumulation were significantly increased) with regards to their expression of phenotypic and functional markers using day 49 Goodpasture syndrome (GPS) rats. Within the renal cortical interstitium, there were a number of alpha-smooth muscle actin(+) (alpha-SMA(+)) FbLCs, negative for vimentin (VIM) and transforming growth factor-beta 1, and not equipped with well-developed rough endoplasmic reticulum and actin-stress fibers. All of these findings were incompatible with the typical features of granulation tissue alpha-SMA(+) myofibroblasts. On the other hand, FbLCs negative for alpha-SMA and VIM produced alpha1(I) procollagen in the nephritic kidney. A number of FbLC populations reside within the cortical interstitium of the kidney in GPS rats, each of which is likely to have developed independently in response to the local conditions of the nephritic kidney, contributing to renal fibrogenesis. Further studies are needed to clarify the key type of FbLC that orchestrates other members to produce renal fibrosis.

  4. Ruptured renal cell carcinoma in pregnancy: a rare case presentation

    Directory of Open Access Journals (Sweden)

    Prameela RC

    2016-05-01

    Full Text Available Malignancy in pregnancy is rare. Carcinomas in pregnancy are mostly kidney cell mass. Renal cell carcinoma (RCC is the commonest malignancy in pregnancy. Because of softness and increased vascularity, rupture of renal cell carcinoma is not uncommon. Here we are presenting a rare case of renal cell carcinoma in pregnancy with spontaneous rupture resulting in massive hemoperitoneum and serious outcome because of late presentation renal cell carcinoma seldom ruptures. A 26 year old woman G2P1L1 with term pregnancy was referred to hospital 80kms away from periphery with non-progression of labour. There was antenatal record suggesting hypertensive disorder of pregnancy in second trimester. On examination, patient was in hypovolemic shock with profuse distension of abdomen. Diagnosis of abruption grade 3 or rupture uterus was made and immediate laparotomy was done. On opening the abdomen, there was hemoperitoneum but uterus was intact. Emergency LSCS done extracted a stillborn baby. There were no retro placental clots also. There was lot of necrotic tissue in the abdomen and there was a tumour arising from lower pole of left kidney which had invaded the renal vessels and had ruptured. Peripartum hysterectomy and left nephrectomy was done. Women did not respond to treatment and died. The objective of presenting this case is the dilemmas faced by the obstetrician in case of shock in 2nd stage of labour. Simple diagnostic tool like renal ultrasound will help to detect at an early stage which could improve the outcome. All cases of hypertensive disorders of pregnancy should be investigated for secondary causes of hypertension. Abdominal USG must be done for all cases of hypertensive disorders of pregnancy in 2nd trimester. Prompt diagnosis and early treatment is the key in management of such condition in pregnancy. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1677-1679

  5. Cell cycle regulatory factors in juxta-tumoral renal parenchyma.

    Science.gov (United States)

    Petruşcă, Daniela Nicoleta; Petrescu, Amelia; Vrabie, Camelia; Niculescu, L; Jinga, V; Diaconu, Carmen; Braşoveanu, Lorelei

    2005-01-01

    The aim of this study was to evaluate regulatory cell cycle factors in juxta-tumoral renal parenchyma in order to obtain information regarding early primary changes occurred in normal renal cells. Specimens of juxta-tumoral renal parenchyma were harvested from the tumoral kidney in 10 patients with no history of treatment before surgery. The expression of p53, Bcl-2, Rb and PCNA was studied by immunohistochemical methods in paraffin-embedded tissues. The apoptotic status was evaluated by flow-cytometry analysis following propidium iodide incorporation. The p53 protein expression was recognized in most of the cases (80%) with different intensities. High intensity apoptotic process detected in juxta-tumoral parenchyma seemed to be p53 dependent and well correlated with the low Bcl-2 expression. 70% of cases were Rb positive. In this type of tissue Rb has only an anti-proliferative and anti-tumoral role. PCNA was present in half of the cases being low expressed due to the tissue regenerating mechanism. Our data suggest that the high intensity of programmed cell death in this type of tissue is supported by the status of cell regulatory factors that control this process. Previous studies have demonstrated that healthy renal tissue has neither apoptosis nor mitotic activity. Juxta-tumoral renal tissue is also displaying normal morphology and DNA content (diploidy) but the microenvironmental status induced by the tumor presence prompts cells to choose death rather than malignant transformation. Further studies are necessary to emphasize if these results have a clinical relevance for the outcome of therapeutical approaches in renal carcinomas.

  6. Immunotherapy for metastatic renal cell carcinoma.

    Science.gov (United States)

    Unverzagt, Susanne; Moldenhauer, Ines; Nothacker, Monika; Roßmeißl, Dorothea; Hadjinicolaou, Andreas V; Peinemann, Frank; Greco, Francesco; Seliger, Barbara

    2017-05-15

    Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients.In November 2015, nivolumab, a checkpoint inhibitor directed against programmed death-1 (PD-1), was approved as the first specific immunotherapeutic agent as second-line therapy in previously treated mRCC patients. To assess the effects of immunotherapies either alone or in combination with standard targeted therapies for the treatment of metastatic renal cell carcinoma and their efficacy to maximize patient benefit. We searched the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), ISI Web of Science and registers of ongoing clinical trials in November 2016 without language restrictions. We scanned reference lists and contacted experts in the field to obtain further information. We included randomized controlled trials (RCTs) and quasi-RCTs with or without blinding involving people with mRCC. We collected and analyzed studies according to the published protocol. Summary statistics for the primary endpoints were risk ratios (RRs) and mean differences (MD) with their 95% confidence intervals (CIs). We rated the quality of evidence using GRADE methodology and summarized the quality and magnitude of relative and absolute effects for each primary outcome in our 'Summary of findings' tables. We identified eight studies with 4732 eligible participants and an additional 13 ongoing studies. We categorized studies into comparisons, all against standard therapy accordingly as first-line (five comparisons) or second-line therapy (one comparison

  7. Magnetic Resonance Imaging as a Biomarker for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Wu

    2015-01-01

    Full Text Available As the most common neoplasm arising from the kidney, renal cell carcinoma (RCC continues to have a significant impact on global health. Conventional cross-sectional imaging has always served an important role in the staging of RCC. However, with recent advances in imaging techniques and postprocessing analysis, magnetic resonance imaging (MRI now has the capability to function as a diagnostic, therapeutic, and prognostic biomarker for RCC. For this narrative literature review, a PubMed search was conducted to collect the most relevant and impactful studies from our perspectives as urologic oncologists, radiologists, and computational imaging specialists. We seek to cover advanced MR imaging and image analysis techniques that may improve the management of patients with small renal mass or metastatic renal cell carcinoma.

  8. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Mahesh Deshmukh

    2011-01-01

    Full Text Available Tubulocystic renal cell carcinoma (TCRCC is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

  9. Renal Cell Carcinoma Mimicking Adrenal Tumor

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Moslemi

    2010-01-01

    Full Text Available There are a variety of causes of adrenal pseudotumors on computerized tomography (CT scan, including upper-pole renal mass, gastric diverticulum, prominent splenic lobulation, pancreatic mass, hepatic mass, and periadrenal varices. We present a case of a large subhepatic mass that discrimination of its origin from neighborhood organs was difficult preoperatively. Our patient was a 58 years old man, that three months after an unsuccessful operation in another center for a pseudoadrenal mass underwent a very difficult subcapsular tumorectomy in our center.

  10. Primary renal carcinoid tumor mimicking non-clear cell renal cell carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Lee Hi; Kim, See Hyung; Kim, Mi Jeong; Choe, Mi Sun [Keimyung University School of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of)

    2016-07-15

    Carcinoid tumors are neoplasms with neuroendocrine differentiation, and they are most commonly found in the gastrointestinal and respiratory systems. Primary renal carcinoid tumor has rarely been reported. Here, we present a case of primary renal carcinoid tumor manifesting as a small but a gradually enhancing mass with calcification and a cystic component.

  11. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Energy Technology Data Exchange (ETDEWEB)

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  12. Metastatic renal cell carcinoma masquerading as a primary ovarian mass in a post-operative case of meningioma and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sangita Bohara

    2015-09-01

    Full Text Available The clinical presentation of metastatic renal cell carcinoma to ovary is extremely rare as well as confusing due to its close resemblance to primary ovarian tumors, especially clear cell carcinoma. We present a case of metastatic renal cell carcinoma diagnosed in a 48-year-old female, who had renal cell carcinoma of the right kidney and right sphenoid wing meningioma of transitional type.

  13. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer

    OpenAIRE

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-01-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormal...

  14. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

    Directory of Open Access Journals (Sweden)

    Verzoni E

    2014-03-01

    Full Text Available Elena Verzoni, Paolo Grassi, Isabella Testa, Roberto Iacovelli, Pamela Biondani, Enrico Garanzini , Filippo De Braud, Giuseppe ProcopioDepartment of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials.Keywords: axitinib, renal cell carcinoma, vascular endothelial growth factor receptor, angiogenesis

  15. The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

    NARCIS (Netherlands)

    Davis, Caleb F; Ricketts, Christopher J; Wang, Min; Yang, Lixing; Cherniack, Andrew D; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C; Hacker, Kathryn E; Bhanot, Gyan; Gordenin, Dmitry A; Chu, Andy; Gunaratne, Preethi H; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A; Bristow, Christopher A; Donehower, Lawrence A; Wallen, Eric M; Smith, Angela B; Tickoo, Satish K; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S; Hsieh, James J; Choueiri, Toni K; Hakimi, A Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A Gordon; Laird, Peter W; Henske, Elizabeth P; Kwiatkowski, David J; Park, Peter J; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A; Linehan, W Marston; Gibbs, Richard A; Rathmell, W Kimryn; Creighton, Chad J

    2014-01-01

    We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared

  16. Saudi Oncology Society clinical management guidelines for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Shouki Bazarbashi

    2011-01-01

    Full Text Available In this report, guidelines for the evaluation, medical and surgical management of renal cell carcinoma is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The recommendations are presented with supporting evidence level.

  17. Alcoholic beverages and risk of renal cell cancer

    NARCIS (Netherlands)

    Greving, J. P.; Lee, J. E.; Wolk, A.; Lukkien, C.; Lindblad, P.; Bergstrom, A.

    2007-01-01

    Using a mailed questionnaire, we investigated the risk of renal cell cancer in relation to different types of alcoholic beverages, and to total ethanol in a large population- based case - control study among Swedish adults, including 855 cases and 1204 controls. Compared to non- drinkers, a total

  18. Renal Cell Carcinoma in a Pregnant Woman With Horseshoe Kidney

    Directory of Open Access Journals (Sweden)

    Anna Scavuzzo

    2017-07-01

    Full Text Available To our knowledge, this is the first reported case of renal cell carcinoma in kidney horseshoe diagnosed in the second trimester of pregnancy. We performed open radical nephrectomy when the pregnancy was completed. Kidney cancer is rare during pregnancy and the symptoms can be mimic urinary infection. The diagnosis and its management can be a challenge.

  19. Obstructive renal injury: from fluid mechanics to molecular cell biology

    Directory of Open Access Journals (Sweden)

    Alvaro C Ucero

    2010-04-01

    Full Text Available Alvaro C Ucero1,*, Sara Gonçalves2,*, Alberto Benito-Martin1, Beatriz Santamaría1, Adrian M Ramos1, Sergio Berzal1, Marta Ruiz-Ortega1, Jesus Egido1, Alberto Ortiz11Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain; 2Nefrologia e Transplantação Renal, Hospital de Santa Maria EPE, Lisbon, Portugal *Both authors contributed equally to the manuscriptAbstract: Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1 and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.Keywords: urinary tract obstruction, renal injury, fluid mechanics, molecular cell biology

  20. Lithium causes g2 arrest of renal principal cells

    NARCIS (Netherlands)

    Groot, T. de; Alsady, M.; Jaklofsky, M.T.; Otte-Holler, I.; Baumgarten, R.; Giles, R.H.; Deen, P.M.T.

    2014-01-01

    Vasopressin-regulated expression and insertion of aquaporin-2 channels in the luminal membrane of renal principal cells is essential for urine concentration. Lithium affects urine concentrating ability, and approximately 20% of patients treated with lithium develop nephrogenic diabetes insipidus (ND

  1. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.

    Science.gov (United States)

    Chen, Jun-Feng; Wu, Qi-Shun; Xie, Yu-Xian; Si, Bo-Lin; Yang, Ping-Ping; Wang, Wen-Yan; Hua, Qin; He, Qing

    2017-10-01

    Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria. © FASEB.

  2. Eplerenone-Mediated Aldosterone Blockade Prevents Renal Fibrosis by Reducing Renal Inflammation, Interstitial Cell Proliferation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2013-11-01

    Full Text Available Background/Aims: Prolonged elevation of serum aldosterone leads to renal fibrosis. Inflammation also plays a role in the pathogenesis of renal disease. We used a rat model of interstitial renal fibrosis to test the hypothesis that eplerenone-mediated aldosterone blockade prevents renal fibrosis due to its anti-inflammatory and anti-proliferative effects. Methods: Eplerenone (a selective aldosterone blocker or vehicle (control, was given to male Wistar rats (50 mg/kg, twice daily for 7 days before unilateral ureteral obstruction (UUO and for an additional 28 days after surgery. Body weight, blood pressure, renal histo-morphology, immune-staining for macrophages, monocyte chemotactic protein-1, proliferating cell nuclear antigen, α-smooth muscle actin, and serum and urine markers of renal function and oxidative stress were determined for both groups on 7, 14, and 28 days after surgery. Results: Epleronone had no effect on body weight or blood pressure. However, eplerenone inhibited the development of renal fibrosis, inflammation (macrophage and monocyte infiltration, interstitial cell proliferation, and activation of interstitial cells (α-SMA expression. Epleronone also reduced oxidative stress. Conclusion: The anti-fibrotic effect of eplerenone appears to be unrelated to its effect on blood pressure. Eplerenone inhibits renal inflammation, interstitial cell proliferation, phenotypic changes of interstitial cells, and reduces oxidative stress.

  3. Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Turker Acar

    2014-01-01

    Full Text Available Epithelioid angiomyolipoma (E-AML, accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC. In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

  4. UOK 268 Cell Line for Hereditary Leiomyomatosis and Renal Cell Carcinoma | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute’s Urologic Oncology Branch seeks parties to co-develop the UOK 262 immortalized cell line as research tool to study aggressive hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated recurring kidney cancer.

  5. Tubulocystic renal cell carcinoma: a new radiological entity

    Energy Technology Data Exchange (ETDEWEB)

    Cornelis, F.; Grenier, N. [Pellegrin Hospital, Department of Radiology, Bordeaux (France); Helenon, O.; Correas, J.M. [Necker Hospital, Department of Radiology, Paris (France); Lemaitre, L. [Claude Huriez Hospital, Department of Radiology, Lille (France); Andre, M. [La-Conception Hospital, Department of Radiology, Marseille (France); Meuwly, J.Y. [Centre Hospitalier Universitaire Vaudois, Department of Radiology, Lausanne (Switzerland); Sengel, C. [Grenoble Hospital, Department of Radiology, Grenoble (France); Derchi, L. [Universita di Genova, Radiologia - DICMI, Genova (Italy); Yacoub, M. [Pellegrin Hospital, Department of Pathology, Bordeaux (France); Verkarre, V. [Necker Hospital, Department of Pathology, Paris (France)

    2016-04-15

    Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal malignancy. While approximately 100 cases of TC-RCC have been reported in the pathology literature, imaging features have not yet been clearly described. The purpose of this review is to describe the main radiologic features of this rare sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective HIPAA-compliant review of pathology and imaging databases. Using a combination of sonographic and CT/MRI features, diagnosis of TC-RCC appeared to be strongly suggested in many cases. (orig.)

  6. Remanent cell traction force in renal vascular smooth muscle cells induced by integrin-mediated mechanotransduction

    OpenAIRE

    Balasubramanian, Lavanya; Lo, Chun-Min; Sham, James S. K.; Yip, Kay-Pong

    2013-01-01

    It was previously demonstrated in isolated renal vascular smooth muscle cells (VSMCs) that integrin-mediated mechanotransduction triggers intracellular Ca2+ mobilization, which is the hallmark of myogenic response in VSMCs. To test directly whether integrin-mediated mechanotransduction results in the myogenic response-like behavior in renal VSMCs, cell traction force microscopy was used to monitor cell traction force when the cells were pulled with fibronectin-coated or low density lipoprotei...

  7. Utility of MRI features in differentiation of central renal cell carcinoma and renal pelvic urothelial carcinoma.

    Science.gov (United States)

    Wehrli, Natasha E; Kim, Min Ju; Matza, Brent W; Melamed, Jonathan; Taneja, Samir S; Rosenkrantz, Andrew B

    2013-12-01

    The purpose of this article is to evaluate the utility of various morphologic and quantitative MRI features in differentiating central renal cell carcinoma (RCC) from renal pelvic urothelial carcinoma. Sixty patients (39 men and 21 women; mean [± SD] age, 65 ± 14 years; 48 with central RCC and 12 with renal pelvic urothelial carcinoma) who underwent MRI, including diffusion-weighted imaging (b values, 0, 400, and 800 s/mm(2)) and dynamic contrast-enhanced imaging, before histopathologic confirmation were included. Tumor T2 signal intensity and apparent diffusion coefficients (ADCs) were measured and normalized to muscle and CSF (hereafter referred to as normalized T2 signal and normalized ADC, respectively) and then were compared using receiver operating characteristic analysis. Also, two blinded radiologists independently assessed all tumors for various qualitative features, which were compared with the Fisher exact test and unpaired Student t test. Urothelial carcinoma exhibited significantly lower normalized ADC than did RCC (p = 0.008), but no significant difference was seen in ADC or normalized T2 signal intensity (p = 0.247-0.773). Normalized ADC had the highest area under the curve (0.757); normalized ADC below an optimal threshold of 0.451 was associated with sensitivity of 83% and specificity of 71% for diagnosing urothelial carcinoma. Features that were significantly more prevalent in urothelial carcinoma included global impression of urothelial carcinoma, location centered within the collecting system, collecting system defect, extension to the ureteropelvic junction, preserved renal shape, absence of cystic or necrotic areas, absence of hemorrhage, homogeneous enhancement, and hypovascularity (all p features ranged from 61.7% to 98.3%. In addition to various qualitative MRI parameters, normalized ADC has utility in differentiating central RCC from renal pelvic urothelial carcinoma. Such differentiation may assist decisions regarding possible biopsy

  8. Expression of lactate dehydrogenase C correlates with poor prognosis in renal cell carcinoma.

    Science.gov (United States)

    Hua, Yibo; Liang, Chao; Zhu, Jundong; Miao, Chenkui; Yu, Yajie; Xu, Aimin; Zhang, Jianzhong; Li, Pu; Li, Shuang; Bao, Meiling; Yang, Jie; Qin, Chao; Wang, Zengjun

    2017-03-01

    Lactate dehydrogenase C is an isoenzyme of lactate dehydrogenase and a member of the cancer-testis antigens family. In this study, we aimed to investigate the expression and functional role of lactate dehydrogenase C and its basic mechanisms in renal cell carcinoma. First, a total of 133 cases of renal cell carcinoma samples were analysed in a tissue microarray, and Kaplan-Meier survival curve analyses were performed to investigate the correlation between lactate dehydrogenase C expression and renal cell carcinoma progression. Lactate dehydrogenase C protein levels and messenger RNA levels were significantly upregulated in renal cell carcinoma tissues, and the patients with positive lactate dehydrogenase C expression had a shorter progression-free survival, indicating the oncogenic role of lactate dehydrogenase C in renal cell carcinoma. In addition, further cytological experiments demonstrated that lactate dehydrogenase C could prompt renal cell carcinoma cells to produce lactate, and increase metastatic and invasive potential of renal cell carcinoma cells. Furthermore, lactate dehydrogenase C could induce the epithelial-mesenchymal transition process and matrix metalloproteinase-9 expression. In summary, these findings showed lactate dehydrogenase C was associated with poor prognosis in renal cell carcinoma and played a pivotal role in the migration and invasion of renal cell carcinoma cells. Lactate dehydrogenase C may act as a novel biomarker for renal cell carcinoma progression and a potential therapeutic target for the treatment of renal cell carcinoma.

  9. Wnt and planar cell polarity signaling in cystic renal disease.

    Science.gov (United States)

    Goggolidou, Paraskevi

    2014-01-01

    Cystic kidney diseases can cause end stage renal disease, affecting millions of individuals worldwide. They may arise early or later in life, are characterized by a spectrum of symptoms and can be caused by diverse genetic defects. The primary cilium, a microtubule-based organelle that can serve as a signaling antenna, has been demonstrated to have a significant role in ensuring correct kidney development and function. In the kidney, one of the signaling pathways that requires the cilium for normal development is Wnt signaling. In this review, the roles of primary cilia in relation to canonical and non-canonical Wnt/PCP signaling in cystic renal disease are described. The evidence of the associations between cilia, Wnt signaling and cystic renal disease is discussed and the significance of planar cell polarity-related mechanisms in cystic kidney disease is presented. Although defective Wnt signaling is not the only cause of renal disease, research is increasingly highlighting its importance, encouraging the development of Wnt-associated diagnostic and prognostic tools for cystic renal disease.

  10. Solitary Contralateral Adrenal Metastases after Nephrectomy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Nikolaos Antoniou

    2004-01-01

    Full Text Available Two cases are reported of patients with a single metastasis in the contralateral adrenal, one and nine years respectively after nephrectomy for localized cancer in the opposite kidney. These types of metastases are usually asymptomatic they do not appear with signs of adrenal insufficiency, they are detected incidentally and the diagnosis is confirmed mainly with CT scan, which comprises the method of choice for the detection of such types of metastases. Many adrenal metastases probably have been overlooked in the past when advanced imaging techniques were not available. Both patients underwent adrenalectomy and replacement therapy with corticosteroids. Approximately 50% of all patients with renal cell carcinoma either present with metastases at diagnosis or will have metastatic disease after nephrectomy11. In order of decreasing frequency, the most common metastatic sites are the lungs, lymph nodes, liver, bone, contralateral kidney and ipsilateral adrenal glands. Adrenal involvement has been reported in 7 to 19% of autopsystudies. 1,3 Solitary metachronous metastatic involvement of the contralateral adrenal from renal cell carcinoma is rarely diagnosed during life and only 4 cases have been reported. 4,5 Recent advances in imaging techniques have allowed the diagnosis of adrenal involvement by renal cancer. Two cases of contralateral adrenal metastasis are reported 1 and 9 years after radical nephrectomy for localized renal cell carcinoma. Both patients underwent adrenalectomy and steroid replacement therapy.

  11. Synchronous Bilateral Adrenal Metastases from Papillary Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kaan Gokcen

    2014-12-01

    Full Text Available We report a case of synchronous bilateral adrenal metastasis of renal cell carcinoma. The contralateral metastatic adrenal mass was treated by the laparoscopic transperitoneal approach. The renal mass and its huge ipsilateral metastatic adrenal gland were removed en bloc with open procedure. A 54-year-old man presented to our clinic with left-sid renal cell carcinoma synchronously bilateral adrenal metastases. The primary tumor was localized in the upper-mid pole of the kidney. The diagnosis was established preoperatively by computed tomography. The size of the contralateral adrenal mass was 65 x 45 mm, but the ipsilateral metastatic adrenal mass was huge (140 x 65 mm. After all analysis and other scannings for any metastasis, a contralateral lapararoscopic transperitoneal adrenalectomy and a left open nephroadrenalectomy were performed simultaneously. Synchronous bilateral adrenal metastases from primary renal cell carcinoma without another metastasis is very rare. The optimal surgical procedure should be selected according to the metastatic adrenal masses size and the patient%u2019s status.

  12. Polypoid Gallbladder Lesion in the Context of Renal Cell Carcinoma

    OpenAIRE

    Barbara Seeliger MD; Cosimo Callari MD; Michele Diana MD; Didier Mutter MD, PhD, FACS; Jacques Marescaux MD, FACS, HON FRCS, HON FJSES

    2013-01-01

    Introduction. The only curative therapeutic approach for renal cell carcinoma (RCC) is surgery. Laparoscopic surgery for RCC has become an established surgical procedure with equivalent cancer-free survival rate, following the same surgical oncological principles as open surgery. Metastatic RCC of the gallbladder is a rare phenomenon. Hence, there are few reports regarding their management. Case Presentation. We report 2 cases of gallbladder metastasis from clear cell RCC treated by laparosco...

  13. Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

    DEFF Research Database (Denmark)

    Davis, Ian D; Xie, Wanling; Pezaro, Carmel;

    2016-01-01

    BACKGROUND: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. OBJECTIVE: To assess outcomes of 2L according to type....... PATIENT SUMMARY: The pattern of treatment failure might help to predict what the next treatment should be for patients with metastatic renal cell carcinoma....

  14. Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

    2013-01-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions...... is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

  15. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas;

    2015-01-01

    BACKGROUND: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance...... to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily......-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.)....

  16. Review series: The cell biology of renal filtration.

    Science.gov (United States)

    Scott, Rizaldy P; Quaggin, Susan E

    2015-04-27

    The function of the kidney, filtering blood and concentrating metabolic waste into urine, takes place in an intricate and functionally elegant structure called the renal glomerulus. Normal glomerular function retains circulating cells and valuable macromolecular components of plasma in blood, resulting in urine with just trace amounts of proteins. Endothelial cells of glomerular capillaries, the podocytes wrapped around them, and the fused extracellular matrix these cells form altogether comprise the glomerular filtration barrier, a dynamic and highly selective filter that sieves on the basis of molecular size and electrical charge. Current understanding of the structural organization and the cellular and molecular basis of renal filtration draws from studies of human glomerular diseases and animal models of glomerular dysfunction.

  17. Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chiara Paglino

    2011-12-01

    Full Text Available Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs, chronic kidney diseases (also dialysis and transplantation, as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL, Hereditary Papillary Renal Carcinoma (HPRC, Birt-Hogg-Dubé Syndrome (BHD, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC. This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC.

  18. Laparoscopic bilateral nephroureterectomy and bladder cuff excision for native renal pelvic and ureteral transitional cell carcinoma after renal transplantation.

    Directory of Open Access Journals (Sweden)

    Chen C

    2003-01-01

    Full Text Available A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

  19. Differentiation of Renal Oncocytoma and Renal Clear Cell Carcinoma Using Relative CT Enhancement Ratio

    Directory of Open Access Journals (Sweden)

    An Ren

    2015-01-01

    Full Text Available Background: The difference between renal oncocytomas (RO and renal clear cell carcinomas (RCCs presents the greatest diagnostic challenge. The aim of this study was to retrospectively determine if RO and RCCs could be differentiated on computed tomography (CT images on the basis of their enhancement patterns with a new enhancement correcting method. Methods: Forty-six patients with a solitary renal mass who underwent total or partial nephrectomy were included in this study. Fourteen of those were RO and 32 were RCCs. All patients were examined with contrast-enhanced CT. The pattern and degree of enhancement were evaluated. We selected the area that demonstrated the greatest degree of enhancement of the renal lesion in the corticomedullary nephrographic and excretory phase images. Regions of interest (ROI were also placed in adjacent normal renal cortex for normalization. We used the values of the normal renal cortex that were measured at the same time as divisors. The ratios of lesion-to-renal cortex enhancement were calculated for all three phases. The Student′s t-test and Pearson′s Chi-square test were used for statistical analyses. Results: All RCCs masses showed contrast that appeared to be better enhanced than RO on all contrast-enhanced phases of CT imaging, but there was no significant difference in absolute attenuation values between these two diseases (P > 0.05. The ratio of lesion-to-cortex attenuation in the corticomedullary phase showed significantly different values between RO and RCCs. The degree of contrast enhancement in RCCs was equal to or greater than that of the normal renal cortex, but it was less than that of the normal cortex in RO in the corticomedullary phase. The ratio of lesion-to-cortex attenuation in the corticomedullary phase was higher than the cut off value of 1.0 in most RCCs (84%, 27/32 and lower than 1.0 in most RO (93%, 13/14 (P < 0.05. In the nephrographic phase, the ratio of lesion-to-cortex attenuation

  20. General Information about Transitional Cell Cancer of the Renal Pelvis and Ureter

    Science.gov (United States)

    ... Renal Pelvis and Ureter Treatment (PDQ®)–Patient Version General Information About Transitional Cell Cancer of the Renal ... through the urethra and leaves the body. Enlarge Anatomy of the male urinary system (left panel) and ...

  1. c-Met in chromophobe renal cell carcinoma.

    Science.gov (United States)

    Erlmeier, Franziska; Ivanyi, Philipp; Hartmann, Arndt; Autenrieth, Michael; Wiedemann, Max; Weichert, Wilko; Steffens, Sandra

    2017-02-01

    c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for c-Met expression by immunohistochemistry. Expression data were associated with clinicopathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis. Twenty-four (29.6%) patients showed a high c-Met expression (c-Met(high), staining intensity higher than median). Our results showed an association between c-Met(high) expression and the existence of lymph node metastasis (p = 0.007). No further significant clinicopathological associations with c-Met were identified, also regarding c-Met expression and overall survival. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of c-Met in a considerably large cohort of chRCC. High c-Met expression is associated with the occurrence of lymph node metastasis. This indicates that c-Met might be implicated into metastatic progression in chRCC.

  2. Reduced expression of Slit2 in renal cell carcinoma.

    Science.gov (United States)

    Ma, Wei-Jie; Zhou, Yu; Lu, Dan; Dong, Dong; Tian, Xiao-Jun; Wen, Jie-Xi; Zhang, Jun

    2014-01-01

    Slit2, initially identified as an important axon guidance molecule in the nervous system, was suggested to be involved in multiple cellular processes. Recently, Slit2 was reported to function as a potential tumor suppressor in diverse tumors. In this study, we systematically analyzed the expression level of Slit2 in renal cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2 mRNA and protein expression were significantly down-regulated in renal cell carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation dramatically induced Slit2 expression in cancer cell lines with weak expression of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation was observed in 8 out of 38 patients (21.1 %), which was well correlated with the down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor suppressor in RCC, which is down-regulated in RCC partially due to promoter methylation.

  3. Human renal medullary interstitial cells and analgesic nephropathy.

    Science.gov (United States)

    Whiting, P H; Tisocki, K; Hawksworth, G M

    1999-01-01

    The aim of this study was to investigate the effects of known papillotoxins using cultures of human renal interstital medullary cells (hRMIC). The culture of hMIC was based on the primary culture of human renal medullary explants, selective detachment of interstitial cells and selective overgrowth of these cells in a serum-rich medium after dilution cloning. The homogeneous population of cells obtained exhibited the characteristic morphological and functional characteristics of Type I interstitial cells, viz. stellate-shaped cells demonstrating numerous lipid droplets, abundant endoplasmic reticulum and mitochondria, fine filaments underlying the cell membrane and the production of extracellular matrix. Cytotoxicity studies using hMIC and known papillotoxins clearly demonstrated a reduction in cell viability that varied with bath exposure time and type of agent tested. While only phenylbutazone and mefenamic acid produced significant cytotoxicity after a 24 h incubation period, cell viability assessed using the MTT assay was only profoundly reduced by aspirin and paracetamol following sub-chronic exposure for 7 days. The rank order of cytotoxicity observed in hMIC was phenylbutazone > mefenamic acid > aspirin > paracetamol. The results demonstrate the potential of hMIC for investigating and defining the early cellular events in the pathogenesis of analgesic nephropathy.

  4. Cadherin-11 in renal cell carcinoma bone metastasis.

    Directory of Open Access Journals (Sweden)

    Robert L Satcher

    Full Text Available Bone is one of the common sites of metastases from renal cell carcinoma (RCC, however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected. The expression of molecules affecting cell adhesion, angiogenesis, and osteolysis were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin mainly expressed in osteoblasts, was significantly increased on the cell surface in bone metastasis-derived 786-O cells (Bo-786-O compared to parental, liver, or lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently expressed in cells derived from all organs. No significant difference was observed in the expression of angiogenic factors, including HIF-1α, VEGF, angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo-786-O cells showed an increase in migration compared to the parental 786-O cells. Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O cells, suggesting that Cadherin-11 contributes to the increased migration observed in bone-derived cells. Immunohistochemical analysis of cadherin-11 expression in a human renal carcinoma tissue array showed that the number of human specimens with positive cadherin-11 activity was significantly higher in tumors that metastasized to bone than that in primary tumors. Together, these results suggest that Cadherin-11 may play a role in RCC bone metastasis.

  5. A Unique Presentation of an Undiagnosed Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Georgios Kravvas

    2014-01-01

    Full Text Available We describe a 58-year-old lady who presented initially to her general practitioner with a palpable warty urethral nodule. She was subsequently referred to the urology department for further investigations. She underwent flexible cystoscopy and imaging, followed by rigid cystoscopy and excision of the nodule. Histological analysis was consistent with renal cell carcinoma (RCC. CT imaging confirmed the presence of an invading metastatic left renal cell carcinoma with bilateral metastatic deposits to the lungs and adrenal glands. The patient was enlisted on the Panther Trial and received a course of Pazopanib before undergoing radical nephrectomy. Two years later she is still alive with metastases remaining reduced in size and numbers. During this study we have performed a literature review of similar cases with this unusual presentation of RCC.

  6. Renal cell carcinoma: Review of etiology, pathophysiology and risk factors.

    Science.gov (United States)

    Petejova, Nadezda; Martinek, Arnost

    2016-06-01

    The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.

  7. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B;

    2009-01-01

    biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... of the control or nephritis biopsies. Scarce apoptotic tubular cells were seen in 13 of 35 (37%) of the nephritis specimens and in two of five (40%) of the control sections. Within the SLE cohort, patients with TUNEL-positive tubular cells in their renal biopsies had significantly higher activity index scores...

  8. Renal arteriography

    Science.gov (United States)

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Review Date 1/5/2016 Updated by: Jason Levy, ...

  9. Metastasis in renal cell carcinoma: Biology and implications for therapy

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

    Full Text Available Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC, metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.

  10. Role of bone marrow-derived stem cells, renal progenitor cells and ...

    African Journals Online (AJOL)

    Hayam Abdel Meguid El Aggan

    2013-04-06

    Apr 6, 2013 ... renal blood flow; MoAbs, monoclonal antibodies; PE, phycoerythrin; ... entiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple .... tion, was done by the spectrophotometric method.31.

  11. Pulmonary Lymphangitic Carcinomatosis due to Renal Cell Carcinoma.

    Science.gov (United States)

    Guddati, Achuta K; Marak, Creticus P

    2012-05-01

    Renal cell carcinoma is an aggressive disease with a high rate of mortality. It is known to metastasize to the lung, liver, bone and brain. However, manifestation through lymphatic spread to the lungs is rare. Lymphangitic carcinomatosis is commonly observed in malignancies of the breast, lung, pancreas, colon and cervix. It is unusual to observe lymphangitic carcinomatosis of the lungs due to renal cell carcinoma. Lymphangitic carcinomatosis of the lungs may result in severe respiratory distress and may be the direct cause of death. Currently, there are no known modalities of preventing or slowing lymphangitic carcinomatosis besides treating the primary tumor. However, early detection may change the course of the disease and may prolong survival. This is compounded by the difficulty involved in diagnosing lymphangitic carcinomatosis of the lung which frequently involves lung biopsy. Immunohistochemical studies are often used in conjunction with regular histochemistry in ascertaining the primary tumor and in differentiating it from pulmonary metastasis. In this case report, we describe the presentation and clinical course of renal cell carcinoma in a patient which manifested as lymphangitis carcinomatosa of the lungs. The patient underwent surgical resection of the primary tumor with lymph node resection but presented with a fulminant lymphangitic carcinomatosis of the lungs within two weeks. Immunohistochemistry of the tissue obtained by the biopsy confirmed the diagnosis which was subsequently corroborated during his autopsy. This case illustrates the necessity of an urgent follow-up of chemotherapy and immunotherapy in such patients.

  12. Pulmonary Lymphangitic Carcinomatosis due to Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Achuta K. Guddati

    2012-05-01

    Full Text Available Renal cell carcinoma is an aggressive disease with a high rate of mortality. It is known to metastasize to the lung, liver, bone and brain. However, manifestation through lymphatic spread to the lungs is rare. Lymphangitic carcinomatosis is commonly observed in malignancies of the breast, lung, pancreas, colon and cervix. It is unusual to observe lymphangitic carcinomatosis of the lungs due to renal cell carcinoma. Lymphangitic carcinomatosis of the lungs may result in severe respiratory distress and may be the direct cause of death. Currently, there are no known modalities of preventing or slowing lymphangitic carcinomatosis besides treating the primary tumor. However, early detection may change the course of the disease and may prolong survival. This is compounded by the difficulty involved in diagnosing lymphangitic carcinomatosis of the lung which frequently involves lung biopsy. Immunohistochemical studies are often used in conjunction with regular histochemistry in ascertaining the primary tumor and in differentiating it from pulmonary metastasis. In this case report, we describe the presentation and clinical course of renal cell carcinoma in a patient which manifested as lymphangitis carcinomatosa of the lungs. The patient underwent surgical resection of the primary tumor with lymph node resection but presented with a fulminant lymphangitic carcinomatosis of the lungs within two weeks. Immunohistochemistry of the tissue obtained by the biopsy confirmed the diagnosis which was subsequently corroborated during his autopsy. This case illustrates the necessity of an urgent follow-up of chemotherapy and immunotherapy in such patients.

  13. Surgical Treatment of Pancreatic Metastases of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Molmenti E

    2005-07-01

    Full Text Available CONTEXT: The pancreas is an unusual site for metastases of renal cell carcinoma origin, sometimes occurring many years after nephrectomy. We herein present two cases of pancreatic metastases of renal cell carcinoma which occurred 17 and 19 years after the primary diagnosis. CASE REPORT: In the first case, metastases were found in the head of the pancreas, upper right arm and the right lobe of the thyroid gland. In the second case, a tumor was found in the tail of the pancreas and a remnant of the right kidney. This was the third recurrence of the original tumor after an initial left nephrectomy and two subsequent partial right nephrectomies in the past. Treatment in the first case consisted of excision of the tumor in the upper right arm, a Whipple operation, and a thyroidectomy. In the second case, a distal pancreatectomy and remnant right nephrectomy were undertaken. Both patients recovered from the operations without complications and remain free of tumor in follow-up periods of 54 and 8 months respectively. CONCLUSIONS: Resection of renal cell carcinoma metastases involving the pancreas provides satisfactory long-term survival, and should be undertaken whenever possible.

  14. Cell therapy in renal and cardiovascular disease Terapia celular en enfermedades renales y cardiovasculares

    Directory of Open Access Journals (Sweden)

    Juan Manuel Senior Sánchez

    2006-01-01

    Full Text Available Although there have been important advances in the field of molecular biology, the mechanisms responsible for nephrogenesis and the factors that modulate the process of development, proliferation, growth, and maturation during fetal and adult life have not been thoroughly explained. Animals, including mammals, share the intrinsic ability to regenerate tissues and organs as an important biological defense mechanism. In the case of the kidney, after tissue damage secondary to injury, anatomical and functional recovery of integrity is achieved, accompanied by the activation of a complex, poorly understood process, leading to the replacement of damaged tubular cells by functional ones that reorganize tubular architecture. This regeneration and repair process is produced by somatic, exogenous, adult stem cells, and probably by intrinsic renal stem cells, that are responsible for maintaining renal homeostasis Aunque se han logrado grandes avances en el campo de la biología molecular, todavía no se han esclarecido completamente los mecanismos responsables de la organogénesis y los factores que modulan el proceso de desarrollo, proliferación, crecimiento y maduración celulares durante la vida fetal y adulta. Los animales comparten la capacidad de regenerar tejidos y órganos, como un mecanismo biológico importante de defensa. En el caso del riñón, luego del daño tisular secundario a una noxa, se produce recuperación anatómica y funcional de la integridad, acompañada por la activación de un proceso sofisticado, mal comprendido, que lleva al reemplazo de las células tubulares dañadas por otras funcionalmente normales que reorganizan la arquitectura tubular. Este fenómeno de recambio se produce gracias a la presencia de células madre adultas somáticas exógenas, responsables del proceso de mantenimiento de la homeostasis renal, y posiblemente por células renales intrínsecas.

  15. Intravenous renal cell transplantation with SAA1-positive cells prevents the progression of chronic renal failure in rats with ischemic-diabetic nephropathy.

    Science.gov (United States)

    Kelly, Katherine J; Zhang, Jizhong; Han, Ling; Wang, Mingsheng; Zhang, Shaobo; Dominguez, Jesus H

    2013-12-15

    Diabetic nephropathy, the most common cause of progressive chronic renal failure and end-stage renal disease, has now reached global proportions. The only means to rescue diabetic patients on dialysis is renal transplantation, a very effective therapy but severely limited by the availability of donor kidneys. Hence, we tested the role of intravenous renal cell transplantation (IRCT) on obese/diabetic Zucker/SHHF F1 hybrid (ZS) female rats with severe ischemic and diabetic nephropathy. Renal ischemia was produced by bilateral renal clamping of the renal arteries at 10 wk of age, and IRCT with genetically modified normal ZS male tubular cells was given intravenously at 15 and 20 wk of age. Rats were euthanized at 34 wk of age. IRCT with cells expressing serum amyloid A had strong and long-lasting beneficial effects on renal function and structure, including tubules and glomeruli. However, donor cells were found engrafted only in renal tubules 14 wk after the second infusion. The results indicate that IRCT with serum amyloid A-positive cells is effective in preventing the progression of chronic kidney disease in rats with diabetic and ischemic nephropathy.

  16. F-18 FDG PET in Detecting Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ak, I.; Can, C. [Osmangazi Univ. Medical Faculty, Eskisehir (Turkey). Depts. of Nuclear Medicine and Urology

    2005-12-01

    Purpose: To assess the role of F-18 FDG imaging with a dual head coincidence mode gamma camera (Co-PET) in the detection of renal cell carcinoma (RCC) in patients with renal masses. Material and Methods: An F-18 FDG Co-PET study was performed in 19 patients (7 F, 12 M; mean age 58.15{+-}2.5 years, age range 45-79 years) with suspected primary renal tumors based on conventional imaging techniques, including computed tomography (CT) and ultrasonography (US) before nephrectomy or surgical resection of the mass. Results: Histologically documented RCC was present in 15 patients. Of the 19 patients with suspected primary renal tumors, F-18 FDG Co-PET was true-positive in 13, false-negative in 2, true-negative in 3, and false-positive in 1 patient. Twangiomyolipomas and one renal mass due to infarction and hemorrhage showed a true-negative Co-PET result. The patient with false-positive FDG Co-PET study was diagnosed as xantogranulomatous pyelonephritis. Overall sensitivity, specificity, and accuracy of FDG Co-PET for RCC were 86% (13/15), 75% (3/4), and 84% (16/19), respectively. Positive predictive value for RCC was 92% and negative predictive value 60%. Conclusion: These findings suggest that F-18 FDG Co-PET may have a role in the diagnostic evaluation of patients with RCC and primary staging of disease. Positive F-18 FDG study may be predictive of the presence of RCC. However, a negative study does not exclude the RCC.

  17. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Suture Granuloma Mimicking Renal Cell Carcinoma: Magnetic Resonance Imaging (MRI and Pathologic Correlation

    Directory of Open Access Journals (Sweden)

    İbrahim İlker Öz

    2014-11-01

    Full Text Available Solid renal masses are generally distinguished with contrast enhancement and intratumoral fatty foci by radiological examinations. The present of enhancement is most important criteria for diagnosis of malignant lesions. Generally, a contrast enhanced solid mass in kidney is accepted as a neoplasm. Foreign body granuloma is an extraordinary cause of enhanced solid renal mass. This case of a renal suture granuloma demonstrated peripheral enhanced exophytic renal mass mimic renal cell carcinoma, and underwent surgery. At the solid renal mass with different radiological features, biopsy is an option to determining the necessity of surgery as well as the surgical approach.

  19. 不同培养基对H9亚型禽流感病毒在MDCK细胞上的增殖效果研究%Proliferation of Avian Influenza Virus H9 Subtype in MDCK Cells in Different Culture Media

    Institute of Scientific and Technical Information of China (English)

    张建伟; 史爱华; 沈佳; 景小冬; 章振华; 李林; 姜北宇

    2012-01-01

    [Objective]To screen the best culture media for proliferation of avian influenza virus ( AIV) H9 subtype in MDCK cells. [ Method] The MDCK monolayer cells were respectively cultured in DMEM containing 10% (V/V) newborn calf serum (NBS) ,low -serum culture medium (MEM - MD -611) and serum - free medium (SFE4Mega) and then inoculated with different dilutions of AIV H9 subtype. These three kinds of media containing 10 (Ag/ml trypsin were also used for maintenance culture of AIV. Every 24 h,cytopathic changes were observed and the HA titer of the culture supernatant was also determined. [Result] After 72 -96 h of culture,the HA titers of the culture supernatant derived from the serum - free medium, low - serum culture medium and serum containing medium were in a decreasing manner. [ Conclusion ] The DMEM containing 10% (V/V) newborn calf serum ( NBS),low - serum culture medium (MEM-MD-611) and serum-free medium (SFE4Mega) can be used for proliferation of AIV, and the latter two may be more suitable to prepare AIV culture.%[目的]比较3种培养基对H9亚型禽流感病毒在MDCK细胞上的增殖效果.[方法]采用DMEM+10%血清、低血清培养基(MEM - MD - 611)、无血清培养基(SFE4Mega)3种培养基制备MDCK细胞单层,分别接种不同稀释度的H9亚型禽流感病毒.然后,分别加入含10 μg/ml胰蛋白酶的3种培养基作为维持液,培养病毒,每隔24h观察其细胞病变,并测定上清HA滴度.[结果]在培养72~96 h时,无血清培养基病毒液的HA滴度高于低血清培养基,而低血清培养基则高于含血清培养基.[结论]3种培养基均可用于制备禽流感病毒抗原,其中无血清培养基、低血清培养基更适用于流感病毒抗原的制备.

  20. Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Okano, Kazuhiro, E-mail: kaokano@kc.twmu.ac.jp; Tsuruta, Yuki; Yamashita, Tetsuri; Takano, Mari; Echida, Yoshihisa; Nitta, Kosaku

    2010-11-15

    Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-{beta}1 (TGF-{beta}1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-{beta}1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.

  1. Progressive renal failure due to renal infiltration by BK polyomavirus and leukaemic cells: which is the culprit?

    Science.gov (United States)

    Sangala, Nicholas; Dewdney, Alex; Marley, Nicholas; Cranfield, Tanya; Venkat-Raman, Gopalakrishnan

    2011-02-01

    Renal infiltration with leukaemic cells is a common finding in patients suffering with chronic lymphocytic leukaemia (CLL) but rarely does it lead to significant renal dysfunction. Similarly, BK nephropathy is a recognized cause of graft failure in renal transplant recipients but rarely causes significant disease in native kidneys. In the few reports where leukaemic infiltration of the kidney has led to significant renal impairment, the pathological process causing renal dysfunction is not identified on biopsy. In these cases, it is unclear whether BK polyomavirus (BKV) nephropathy has been excluded. We describe a case of dual pathologies in a patient with Binet stage C CLL and deteriorating renal function where renal biopsy reveals leukaemic infiltration of the kidney occurring alongside BKV nephropathy. The relative importance of each pathology in relation to the rapid decline to end-stage renal failure remains unclear, but the presence of both pathologies appears to impart a poor prognosis. Additionally, we describe the novel histological finding of loss of tubular integrity resulting in tubular infiltration and occlusion by leukaemic cells. It is possible that the patient with advanced CLL is at particular risk of BK activation, and the presence of BK nephropathy may compromise tubular integrity allowing leukaemic cell infiltration and obstruction of tubules. This case bares remarkable resemblance to the first and only other report of its kind in the literature. It is not clear how available immunocytochemistry for polyoma infection is outside transplant centres, and it is possible that BK nephropathy is being under-diagnosed in patients with CLL in the context of declining renal function. At present, the combination of BKV nephropathy and leukaemic infiltration represents a management conundrum and the prognosis is poor. Further research is required in order to better understand the pathological process and therefore develop management strategies.

  2. Occupational Sunlight Exposure and Risk of Renal Cell Carcinoma

    Science.gov (United States)

    Karami, Sara; Boffetta, Paolo; Stewart, Patricia; Rothman, Nathaniel; Hunting, Katherine L.; Dosemeci, Mustafa; Berndt, Sonja I.; Brennan, Paul; Chow, Wong-Ho; Moore, Lee E.; Zaridze, David; Mukeria, Anush; Janout, Vladimir; Kollarova, Helena; Bencko, Vladimir; Holcatova, Ivana; Navritalova, Marie; Szeszenia-Dabrowska, Neonila; Mates, Dana; Gromiec, Jan P.

    2010-01-01

    Background Recent findings indicate that vitamin D obtained from ultraviolet (UV) exposure may reduce the risk of a number of different cancers. Vitamin D is metabolized to its active form within the kidney, the major organ for vitamin D metabolism and activity. Since both the incidence of renal cell cancer and prevalence of vitamin D deficiency have increased over the past few decades, this study sought to explore whether occupational UV exposure was associated with renal cell carcinoma (RCC) risk. Methods A hospital-based case-control study of 1,097 RCC cases and 1,476 controls was conducted in four Central and Eastern European countries. Demographic and occupational information was collected to examine the association between occupational UV exposure and RCC risk. Results A significant (24%-38%) reduction in RCC risk was observed with increasing occupational UV exposure among male participants. No association between UV exposure and RCC risk was observed among female participants. When analyses were stratified by latitude as another estimate of sunlight intensity, a stronger (71%-73%) reduction in RCC risk was observed between UV exposure and cancer risk among males residing at the highest latitudes. Conclusion The results of this study suggest that among males there is an inverse association between occupational UV exposure and renal cancer risk. Replication studies are warranted to confirm these results. PMID:20213683

  3. Renal cell carcinoma: histological classification and correlation with imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Muglia, Valdair F., E-mail: fmuglia@fmrp.usp.br [Universidade de Sao Paulo (CCIFM/FMRP/USP), Ribeirao Preto, SP (Brazil). Centro de Ciencias das Imagens e Fisica Medica. Faculdade de Medicina; Prando, Adilson [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Hospital Vera Cruz, Campinas, SP (Brazil). Dept. de Imaginologia

    2015-05-15

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes. (author)

  4. Tyrosine kinase inhibitors target cancer stem cells in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Solarek, Wojciech; Kornakiewicz, Anna; Szczylik, Cezary

    2016-03-01

    This study was designed to analyze the impact of multi-targeted tyrosine kinase inhibitors on the cancer stem cell subpopulation in renal cell cancer. The second objective was to evaluate the effect of tumor growth inhibition related to a tumor niche factor - oxygen deprivation - as hypoxia develops along with the anti-angiogenic activity of tyrosine kinase inhibitors in renal tumors. Cells were treated with tyrosine kinase inhibitors, sunitinib, sorafenib and axitinib, in 2D and 3D culture conditions. Cell proliferation along with drug toxicity were evaluated. It was shown that the proliferation rate of cancer stem cells was decreased by the tyrosine kinase inhibitors. The efficacy of the growth inhibition was limited by hypoxic conditions and 3D intratumoral cell-cell interactions. We conclude that understanding the complex molecular interaction feedback loops between differentiated cancer cells, cancer stem cells and the tumor microenvironment in 3D culture should aid the identification of novel treatment targets and to evalute the efficacy of renal cancer therapies. Cell-cell interaction may represent a critical microenvironmental factor regulating cancer stem cell self-renewal potential, enhancing the stem cell phenotype and limiting drug toxicity. At the same time the role of hypoxia in renal cancer stem cell biology is also significant.

  5. Renal cell carcinoma-associated adult dermatomyositis treated laparoscopic nephrectomy

    Directory of Open Access Journals (Sweden)

    Elizabeth Nevins

    2013-01-01

    Full Text Available A 77-year-old female, who suffered from rheumatoid arthritis and hypothyroidism, developed severe muscle weakness. Clinical features, blood results and muscle biopsy suggested a possible diagnosis of dermatomyositis. A computed tomography of the chest, abdomen and pelvis showed a solid mass in the left kidney. She underwent a left laparoscopic nephrectomy and histology confirmed conventional (clear cell renal cell carcinoma. She recovered slowly and almost back to normal life after 6 months. Early appreciation of the typical skin rash may provide a clue to the diagnosis and screening for neoplasm may improve prognosis.

  6. Demyelinating Peripheral Neuropathy Due to Renal Cell Carcinoma

    Science.gov (United States)

    Nishioka, Kenya; Fujimaki, Motoki; Kanai, Kazuaki; Ishiguro, Yuta; Nakazato, Tomoko; Tanaka, Ryota; Yokoyama, Kazumasa; Hattori, Nobutaka

    2017-01-01

    Renal cell carcinoma (RCC) patients who develop a paraneoplastic syndrome may present with neuromuscular disorders. We herein report the case of a 50-year-old man who suffered from progressive gait disturbance and muscle weakness. The results of a nerve conduction study fulfilled the criteria of chronic inflammatory demyelinating polyneuropathy. An abdominal CT scan detected RCC, the pathological diagnosis of which was clear cell type. After tumor resection and a single course of intravenous immunoglobulin therapy, the patient's symptoms drastically improved over the course of one year. The patient's neurological symptoms preceded the detection of cancer. A proper diagnosis and the initiation of suitable therapies resulted in a favorable outcome. PMID:28049985

  7. Losartan attenuates renal interstitial fibrosis and tubular cell apoptosis in a rat model of obstructive nephropathy.

    Science.gov (United States)

    He, Ping; Li, Detian; Zhang, Beiru

    2014-08-01

    Ureteral obstruction leads to renal injury and progresses to irreversible renal fibrosis, with tubular cell atrophy and apoptosis. There is conflicting evidence concerning whether losartan (an angiotensin II type I receptor antagonist) mitigates renal interstitial fibrosis and renal tubular epithelial cell apoptosis following unilateral ureteral obstruction (UUO) in animal models. The aim of this study was to investigate the effect and mechanism of losartan on renal tubular cell apoptosis and renal fibrosis in a rat model of UUO. The rats were subjected to UUO by ureteral ligation and were treated with dimethyl sulfoxide (control) or losartan. The controls underwent sham surgery. The renal tissues were collected 3, 5, 7 and 14 days after surgery for measurement of various indicators of renal fibrosis. UUO increased the expression levels of α‑smooth muscle actin and collagen I, and the extent of renal tubular fibrosis and apoptosis in a time‑dependent manner. Losartan treatment partially attenuated these responses. Progression of renal interstitial fibrosis was accompanied by phosphorylation of signal transducer and activator of transcription 3 (STAT3) and altered the expression levels of two apoptosis‑related proteins (Bax and Bcl2). Losartan treatment also partially attenuated these responses. The results indicated that losartan attenuated renal fibrosis and renal tubular cell apoptosis in a rat model of UUO. This effect appeared to be mediated by partial blockage of STAT3 phosphorylation.

  8. MUTATIONS IN THE VHL GENE FRIOM POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMORS

    Science.gov (United States)

    Potassium bromate (KBrO3) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO3 in F344 rats. ...

  9. Regenerative medicine for the kidney: renotropic factors, renal stem/progenitor cells, and stem cell therapy.

    Science.gov (United States)

    Maeshima, Akito; Nakasatomi, Masao; Nojima, Yoshihisa

    2014-01-01

    The kidney has the capacity for regeneration and repair after a variety of insults. Over the past few decades, factors that promote repair of the injured kidney have been extensively investigated. By using kidney injury animal models, the role of intrinsic and extrinsic growth factors, transcription factors, and extracellular matrix in this process has been examined. The identification of renal stem cells in the adult kidney as well as in the embryonic kidney is an active area of research. Cell populations expressing putative stem cell markers or possessing stem cell properties have been found in the tubules, interstitium, and glomeruli of the normal kidney. Cell therapies with bone marrow-derived hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, and amniotic fluid-derived stem cells have been highly effective for the treatment of acute or chronic renal failure in animals. Embryonic stem cells and induced pluripotent stem cells are also utilized for the construction of artificial kidneys or renal components. In this review, we highlight the advances in regenerative medicine for the kidney from the perspective of renotropic factors, renal stem/progenitor cells, and stem cell therapies and discuss the issues to be solved to realize regenerative therapy for kidney diseases in humans.

  10. Renal Cell Carcinoma in A Patient with Kartagener Syndrome: First Case Report in English Language

    Directory of Open Access Journals (Sweden)

    Erkin Sağlam

    2015-03-01

    Full Text Available Cardiac and pulmonary anomalies are common among patients with situs inversus totalis. Renal anomalies, including renal agenesis, dysplasia, hypoplasia, ectopia, polycystic kidney, and horseshoe kidney have been reported. We report a case of renal cell carcinoma in a patient with situs inversus totalis (SIT. Our case represents the fourth case report of renal cell carcinoma in a patient with situs inversus totalis and to the best of our knowledge this is the first report in English language. Due to the higher frequency of cardiac, pulmonary, renal, and vascular anomalies the management of patients with situs inversus and urologic disease requires careful preoperative evaluation.

  11. Biology of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Michele Milella, Alessandra Felici

    2011-01-01

    cell biology and tumor-host interactions may hold the key to future advances in such a complex and challenging disease.

  12. Role of everolimus in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

    Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

  13. Cystic Renal Oncocytoma and Tubulocystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Comparative Study.

    Science.gov (United States)

    Skenderi, Faruk; Ulamec, Monika; Vranic, Semir; Bilalovic, Nurija; Peckova, Kvetoslava; Rotterova, Pavla; Kokoskova, Bohuslava; Trpkov, Kiril; Vesela, Pavla; Hora, Milan; Kalusova, Kristyna; Sperga, Maris; Perez Montiel, Delia; Alvarado Cabrero, Isabel; Bulimbasic, Stela; Branzovsky, Jindrich; Michal, Michal; Hes, Ondrej

    2016-02-01

    Renal oncocytoma (RO) may present with a tubulocystic growth in 3% to 7% of cases, and in such cases its morphology may significantly overlap with tubulocystic renal cell carcinoma (TCRCC). We compared the morphologic and immunohistochemical characteristics of these tumors, aiming to clarify the differential diagnostic criteria, which facilitate the discrimination of RO from TCRCC. Twenty-four cystic ROs and 15 TCRCCs were selected and analyzed for: architectural growth patterns, stromal features, cytomorphology, ISUP nucleolar grade, necrosis, and mitotic activity. Immunohistochemical panel included various cytokeratins (AE1-AE3, OSCAR, CAM5.2, CK7), vimentin, CD10, CD117, AMACR, CA-IX, antimitochondrial antigen (MIA), EMA, and Ki-67. The presence of at least focal solid growth and islands of tumor cells interspersed with loose stroma, lower ISUP nucleolar grade, absence of necrosis, and absence of mitotic figures were strongly suggestive of a cystic RO. In contrast, the absence of solid and island growth patterns and presence of more compact, fibrous stroma, accompanied by higher ISUP nucleolar grade, focal necrosis, and mitotic figures were all associated with TCRCC. TCRCC marked more frequently for vimentin, CD10, AMACR, and CK7 and had a higher proliferative index by Ki-67 (>15%). CD117 was negative in 14/15 cases. One case was weakly CD117 reactive with cytoplasmic positivity. All cystic RO cases were strongly positive for CD117. The remaining markers (AE1-AE3, CAM5.2, OSCAR, CA-IX, MIA, EMA) were of limited utility. Presence of tumor cell islands and solid growth areas and the type of stroma may be major morphologic criteria in differentiating cystic RO from TCRCC. In difficult cases, or when a limited tissue precludes full morphologic assessment, immunohistochemical pattern of vimentin, CD10, CD117, AMACR, CK7, and Ki-67 could help in establishing the correct diagnosis.

  14. [NEOADJUVANT TARGET THERAPY IN A RENAL-CELL CANCER].

    Science.gov (United States)

    Stakhovskiy, E O; Voylenko, O A; Stakhovskiy, O E; Vitruk, Yu V; Vukalovych, P S; Kononenko, O A

    2015-12-01

    There were observed 30 patients (32 tumors), to whom preoperatively for renal-cell cancer (ROC) a neoadjuvant target therapy (NATTH) was conducted. In 19 (66.7%) of them a pazopanib (800 mg per os once a day through 2 mo) was applied, and in 10 (33.3%)--sunitinib (50 mg per os once a day through 28 days, the gap--14 days, repeated course--28 days). The indications for the NATTH conduction were: in 7 (21.9%) patients--a locally--spread RCC with the objective to localize a tumor and to search a further possibility of radical surgical intervention performance, and in 25 (78.1%)--the tumor reduction and searching possibility of the organpreserving treatment conduction. The NATTH conduction in the patients, suffering RCC, have guaranteed a primary pathological focus reduction in 90% of observations, and a partial regression in accordance to the RECIST criteria--in 28.1%. A tumor reduction by (22.9 ± 17.8)% at average have permitted to perform a renal resection in 75% of observations, concerning localized RCC, when indication of preservation of enough functioning renal parenchyma was secured.

  15. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fengju Chen

    2016-03-01

    Full Text Available On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression, we classified 894 renal cell carcinomas (RCCs of various histologic types into nine major genomic subtypes. Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes. Differences in patient survival and in alteration of specific pathways (including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC. Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.

  16. Role of N-glycosylation in renal betaine transport.

    Science.gov (United States)

    Schweikhard, Eva S; Burckhardt, Birgitta C; Joos, Friedericke; Fenollar-Ferrer, Cristina; Forrest, Lucy R; Kempson, Stephen A; Ziegler, Christine

    2015-09-01

    The osmolyte and folding chaperone betaine is transported by the renal Na(+)-coupled GABA (γ-aminobutyric acid) symporter BGT-1 (betaine/GABA transporter 1), a member of the SLC6 (solute carrier 6) family. Under hypertonic conditions, the transcription, translation and plasma membrane (PM) insertion of BGT-1 in kidney cells are significantly increased, resulting in elevated betaine and GABA transport. Re-establishing isotonicity involves PM depletion of BGT-1. The molecular mechanism of the regulated PM insertion of BGT-1 during changes in osmotic stress is unknown. In the present study, we reveal a link between regulated PM insertion and N-glycosylation. Based on homology modelling, we identified two sites (Asn(171) and Asn(183)) in the extracellular loop 2 (EL2) of BGT-1, which were investigated with respect to trafficking, insertion and transport by immunogold-labelling, electron microscopy (EM), mutagenesis and two-electrode voltage clamp measurements in Xenopus laevis oocytes and uptake of radiolabelled substrate into MDCK (Madin-Darby canine kidney) and HEK293 (human embryonic kidney) cells. Trafficking and PM insertion of BGT-1 was clearly promoted by N-glycosylation in both oocytes and MDCK cells. Moreover, association with N-glycans at Asn(171) and Asn(183) contributed equally to protein activity and substrate affinity. Substitution of Asn(171) and Asn(183) by aspartate individually caused no loss of BGT-1 activity, whereas the double mutant was inactive, suggesting that N-glycosylation of at least one of the sites is required for function. Substitution by alanine or valine at either site caused a dramatic loss in transport activity. Furthermore, in MDCK cells PM insertion of N183D was no longer regulated by osmotic stress, highlighting the impact of N-glycosylation in regulation of this SLC6 transporter.

  17. Xp11 translocation renal cell carcinoma morphologically mimicking clear cell-papillary renal cell carcinoma in an adult patient: report of a case expanding the morphologic spectrum of Xp11 translocation renal cell carcinomas.

    Science.gov (United States)

    Parihar, Asmita; Tickoo, Satish K; Kumar, Sunil; Arora, Vinod Kumar

    2015-05-01

    Xp11 translocation renal cell carcinoma (RCC) is a relatively rare tumor mainly affecting children and adolescents. It shows significant morphological overlap with the 2 most common adult renal tumors, which are the clear cell (conventional) RCC and papillary RCC. We describe case of a young adult female who presented with right flank pain and abdominal mass. Radiological investigations showed features suggestive of renal cell carcinoma in the right kidney. Histopathological findings while suggestive of Xp11 carcinoma, showed significant overlap with the recently described entity clear cell papillary RCC. TFE3 immunohistochemistry confirmed the tumor to be Xp11 translocation RCC. The patient had an aggressive course with lymph node metastasis. In this report, we discuss differential diagnosis and the diagnostic challenges of Xp11 translocation RCC in adults.

  18. Bilateral tubulocystic renal cell carcinomas in diabetic end-stage renal disease: first case report with cytogenetic and ultrastructural studies

    Directory of Open Access Journals (Sweden)

    Max Xiangtian Kong

    2013-11-01

    Full Text Available Tubulocystic renal cell carcinoma (TC-RCC is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.

  19. Multiple nephron-sparing procedures in solitary kidney with recurrent, metachronous, nonfamilial renal cell carcinoma.

    Science.gov (United States)

    Nosnik, Israel P; Mouraviev, Vladimir; Nelson, Rendon; Polascik, Thomas J

    2006-12-01

    Patients with metachronous bilateral renal cell carcinoma pose a significant challenge given the high mortality of renal cell carcinoma and the poor quality of life should dialysis become necessary. In addition, patients may be subject to morbidity due to potential multiple treatments of the multifocal renal tumors. We present the case of a 71-year-old woman with multifocal, bilateral clear cell carcinoma who maintained a minimal change in serum creatinine after undergoing unilateral radical nephrectomy, subsequent percutaneous radiofrequency ablation, percutaneous cryoablation, laparoscopic cryoablation, and open partial nephrectomy for recurrent renal cell carcinoma in a solitary kidney.

  20. Renal cell carcinoma metastasis to the cerebellopontine cistern: intraoperative Onyx embolization via direct needle puncture

    National Research Council Canada - National Science Library

    Johnson, Jeremiah; Morcos, Jacques; Elhammady, Mohamed; Pao, Christine L; Aziz-Sultan, Mohammad Ali

    2013-01-01

    We report a rare case of a renal cell carcinoma (RCC) metastasis occupying the cerebellopontine and cerebellomedullary cisterns, and describe an alternative strategy for embolizing hypervascular intracranial tumors...

  1. Microarray gene expression profiling and analysis in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sadhukhan Provash

    2004-06-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

  2. Clear Cell Adenocarcinoma of the Renal Pelvis in a Male Patient

    Directory of Open Access Journals (Sweden)

    Sarawut Kongkarnka

    2013-01-01

    Full Text Available Carcinoma of the renal pelvis is an uncommon renal neoplasm. Clear cell adenocarcinoma in the urinary tract is rare and has a histomorphology resembling that of the female genital tract. We herein present a case of clear cell adenocarcinoma of the renal pelvis, which is the first example in a male patient to our knowledge. A 54-year-old man presented with right flank pain. The tumor was associated with renal stones and hydronephrosis and invaded into the peripelvic fat tissue with regional lymph node metastasis. The patient died of metastatic disease six months postoperatively. Histologically, the tumor showed complex papillary architecture lined with clear and hobnail cells. Clear cell adenocarcinoma of the renal pelvis may pose a diagnostic challenge on histological grounds, particularly in the distinction from renal cell carcinoma. The immunohistochemical stains could help confirm the diagnosis. Due to its rarity, an effective treatment regimen remains to be determined.

  3. Molecular Genetic Alterations in Renal Cell Carcinomas With Tubulocystic Pattern: Tubulocystic Renal Cell Carcinoma, Tubulocystic Renal Cell Carcinoma With Heterogenous Component and Familial Leiomyomatosis-associated Renal Cell Carcinoma. Clinicopathologic and Molecular Genetic Analysis of 15 Cases.

    Science.gov (United States)

    Ulamec, Monika; Skenderi, Faruk; Zhou, Ming; Krušlin, Božo; Martínek, Petr; Grossmann, Petr; Peckova, Kvetoslava; Alvarado-Cabrero, Isabel; Kalusova, Kristyna; Kokoskova, Bohuslava; Rotterova, Pavla; Hora, Milan; Daum, Ondrej; Dubova, Magdalena; Bauleth, Kevin; Slouka, David; Sperga, Maris; Davidson, Whitney; Rychly, Boris; Perez Montiel, Delia; Michal, Michal; Hes, Ondrej

    2016-08-01

    The characteristic morphologic spectrum of tubulocystic renal cell carcinoma (TC-RCC) may include areas resembling papillary RCC (PRCC). Our study includes 15 RCCs with tubulocystic pattern: 6 TC-RCCs, 1 RCC-high grade with tubulocystic architecture, 5 TC-RCCs with foci of PRCC, 2 with high-grade RCC (HGRCC) not otherwise specified, and 1 with a clear cell papillary RCC/renal angiomyoadenomatous tumor-like component. We analyzed aberrations of chromosomes 7, 17, and Y; mutations of VHL and FH genes; and loss of heterozygosity at chromosome 3p. Genetic analysis was performed separately in areas of classic TC-RCC and in those with other histologic patterns. The TC-RCC component demonstrated disomy of chromosome 7 in 9/15 cases, polysomy of chromosome 17 in 7/15 cases, and loss of Y in 1 case. In the PRCC component, 2/3 analyzable cases showed disomy of chromosome 7 and polysomy of chromosome 17 with normal Y. One case with focal HGRCC exhibited only disomy 7, whereas the case with clear cell papillary RCC/renal angiomyoadenomatous tumor-like pattern showed polysomies of 7 and 17, mutation of VHL, and loss of heterozygosity 3p. FH gene mutation was identified in a single case with an aggressive clinical course and predominant TC-RCC pattern. The following conclusions were drawn: (1) TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. (2) The biological nature of PRCC/HGRCC-like areas within TC-RCC remains unclear. Our data suggest that heterogenous TC-RCCs may be associated with an adverse clinical outcome. (3) Hereditary leiomyomatosis-associated RCC can be morphologically indistinguishable from "high-grade" TC-RCC; therefore, in TC-RCC with high-grade features FH gene status should be tested.

  4. Open Partial Nephrectomy in Solitary Kidney with Multiple Renal Cell Carcinoma: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Ji-rui Niu; Quan-zong Mao; Zhi-gang Ji

    2011-01-01

    RENAL cell carcinoma (RCC) in a solitary kidney presents a unique clinical challenge to urological surgeons.Partial nephrectomy (PN) or nephron-sparing surgery in this condition provides good oncological and renal fuctional outcomes with an acceptable complication rate.1,2 Long-term renal function remains stable in most patients with solitary kidneys after a reduction of more than 50% in renal mass.3 PN is a surgical procedure reserved for patients with a tumor in a solitary kidney,bilateral renal tumors,or renal function impairment.4 The challenge of preserving renal parenchyma is significantly complicated with the discovery of multiple masses in a solitary kidney because any subsequent complications may result in a significant decline in quality of life.Particularly in the case of postoperative renal failure,dialysis becomes necessary.

  5. Renal cell carcinoma with metastasis to the submandibular and parotid glands A case report

    NARCIS (Netherlands)

    Smits, J.G.; Slootweg, P.J.

    1984-01-01

    Differential diagnosis between acinic cell carcinoma and renal cell carcinoma is an oft-quoted problem. A case is presented of a 60-year-old woman with metastatic lesions from a renal cell carcinoma to the parotid as well as the submandibular gland. Appropriate diagnosis was delayed due to lack of c

  6. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Directory of Open Access Journals (Sweden)

    K J Kelly

    Full Text Available Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  7. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Science.gov (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  8. Diagnosis and Management of Hereditary Renal Cell Cancer.

    Science.gov (United States)

    Menko, Fred H; Maher, Eamonn R

    2016-01-01

    Renal cell cancer (RCC) is the common denominator for a heterogeneous group of diseases. The subclassification of these tumours is based on histological type and molecular pathogenesis. Insight into molecular pathogenesis has led to the development of targeted systemic therapies. Genetic susceptibility is the principal cause of RCC in about 2-4% of cases. Hereditary RCC is the umbrella term for about a dozen different conditions, the most frequent of which is von Hippel-Lindau disease . Here, we describe the main hereditary RCC syndromes, consider criteria for referral of RCC patients for clinical genetic assessment and discuss management options for patients with hereditary RCC and their at-risk relatives.

  9. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

    OpenAIRE

    Liou, Victor D.; Darwish, Oussama M.; Henry, Mary M.; Jun, Ik C.; Sameer A. Siddiqui

    2015-01-01

    Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC) to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC wh...

  10. THE PURE RED BLOOD CELL APLASIA IN RENAL TRANSPLANT RECIPIENT

    Directory of Open Access Journals (Sweden)

    B. T. Dzumabaeva

    2011-01-01

    Full Text Available The pure red blood cell aplasia of renal transplant recipients caused by parvovirus B19 (PB19 is characterized by persistent anemia which resistant to erythropoietin therapy, lack of reticulocytes, bone marrow hypoplasia, and clinically accompanied by severe recurrent bacterial, fungal and viral infection. In case of reactivation PB19 it is necessarv, first of all, eliminate the causes activation of this virus and to cancel or reduce the dose of drugs which depressed the normal hematopoiesis germs, thus to reduce the pancytopenia associating complications in this population. 

  11. [WHO classification 2016 and first S3 guidelines on renal cell cancer: What is important for the practice?].

    Science.gov (United States)

    Moch, H

    2016-03-01

    The first S3 guidelines on renal cell cancer cover the practical aspects of imaging, diagnostics and therapy as well as the clinical relevance of pathology reporting. This review summarizes the changes in renal tumor classification and the new recommendations for reporting renal cell tumors. The S3 guidelines recommend the 2016 World Health Organization (WHO) classification of renal cell tumors. Novel renal cell tumor entities and provisional or emerging renal cell tumor entities of the 2016 WHO classification of renal tumors are discussed. The S3 guidelines for renal cell cancer also recommend the use of the WHO/International Society of Urologic Pathology (ISUP) grading system for clear cell and for papillary renal cell carcinomas, which replaces the previously used Fuhrman grading system.

  12. {sup 11}C-Acetate PET imaging for renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Kusukawa, Naoya; Kaneda, Taisei; Miwa, Yoshiji; Akino, Hironobu; Yokoyama, Osamu [University of Fukui, Department of Urology, Fukui (Japan); Okazawa, Hidehiko; Fujibayashi, Yasuhisa [University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Yonekura, Yoshiharu [National Institute of Radiological Sciences, Chiba (Japan); Welch, Michael J. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, Saint Louis, MO (United States)

    2009-03-15

    In this study, we investigated the effectiveness of positron emission tomography (PET) with {sup 11}C-acetate (AC) for evaluation of renal cell carcinoma. Enrolled in the study were 20 patients with suspected renal tumour, one of whom had three renal lesions. In all, 22 renal lesions were evaluated. Following administration of 350 MBq (10 mCi) of AC, whole-body PET images were obtained. Based on these PET findings, kidney lesions were scored as positive or negative. The PET results were correlated with the CT findings and histological diagnosis after surgery. In 18 patients, 20 tumours were diagnosed as renal cell carcinoma. Lesions in the remaining two patients were diagnosed as complicated cyst without malignant tissue. Of the 20 renal cell carcinomas. 14 (70%) showed positive AC PET findings; 6 were negative. The two patients with complicated cyst had negative AC PET findings. Of the 20 renal cell carcinomas, 19 were clear-cell carcinoma and 1 was a papillary cell carcinoma. This papillary cell carcinoma showed high AC uptake. AC demonstrates marked uptake in renal cell carcinoma. These preliminary data show that AC is a possible PET tracer for detection of renal cancer. (orig.)

  13. Regulatory T cells, dendritic cells and neutrophils in patients with renal cell carcinoma.

    Science.gov (United States)

    Minárik, Ivo; Lašťovička, Jan; Budinský, Vít; Kayserová, Jana; Spíšek, Radek; Jarolím, Ladislav; Fialová, Anna; Babjuk, Marek; Bartůňková, Jiřina

    2013-05-01

    We evaluated dendritic cells (DC), regulatory T lymphocytes (Treg) and neutrophils in 37 patients with newly diagnosed renal cell carcinoma (RCC) in the tumor and peripheral blood (PB) and correlated these parameters with tumor staging (early-T1, 2, late-T3, 4 and metastatic disease). The number of myeloid and plasmacytoid DC in blood of RCC patients was higher than in healthy controls. The percentage of myeloid dendritic cells (mDC) from CD45+ cells in tumors was higher in comparison with peripheral blood irrespective of disease stage. Higher percentage of these cells expressed a maturation marker in the periphery in the early stage (CD83 expressing cells). The number of plasmacytoid dendritic cells (pDC) in PB was similar in both early and late stage groups, but the early group displayed a significantly higher percentage of pDC in tumor cell suspension. Neutrophil counts in the peripheral blood of RCC patients were higher than in healthy controls, but the counts in both tumor stage groups were similar. The proportion of neutrophils from CD45+ cells was higher in late stage tumors. Higher percentage of Treg from CD4+ cells was detected in renal carcinoma tissue in comparison to PB with no difference between stages of the disease. Our results reflect the complex interplay between various cells of the immune system and the tumor microenvironment. Activation of dendritic cell subpopulations at early stages of the disease course is counterbalanced by the early appearance of T regulatory cells both in the periphery and tumor tissue. Later stages are characterized by the accumulation of neutrophils in the tumor. Appropriate timing of anticancer strategies, especially immunotherapy, should take these dynamics of the immune response in RCC patients into account.

  14. Multiple metastatic renal cell carcinoma isolated to pancreas.

    Science.gov (United States)

    Comunoğlu, Cem; Altaca, Gülüm; Demiralay, Ebru; Moray, Gökhan

    2012-06-01

    Renal cell carcinoma (RCC) metastases to the pancreas are reported to be rare. Isolated multiple pancreatic metastases are even rarer. We report a 68-year-old asymptomatic male patient who presented with multiple metastatic nodular lesions in the pancreas demonstrated by computerized tomography 3.5 years after radical nephrectomy performed for clear cell RCC. Spleen-preserving total pancreatectomy was performed. Gross examination revealed five well-demarcated tumoral nodules in the head, body and tail of the pancreas. Histopathological examination revealed clusters of epithelial clear cells, immunohistochemically positive for CD10 and vimentin, and negative for CK19 and chromogranin, supporting a diagnosis of metastatic RCC. The patient has remained well at 29 months post-resection, in agreement with recent experience that radical resection for multiple isolated metastatic nodular lesions can achieve improved survival and better quality of life.

  15. Obstructive renal injury: from fluid mechanics to molecular cell biology

    Science.gov (United States)

    Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

    2010-01-01

    Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making. PMID:24198613

  16. Obstructive renal injury: from fluid mechanics to molecular cell biology.

    Science.gov (United States)

    Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

    2010-04-22

    Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.

  17. Vasoactive intestinal peptide (VIP) inhibits human renal cell carcinoma proliferation.

    Science.gov (United States)

    Vacas, Eva; Fernández-Martínez, Ana B; Bajo, Ana M; Sánchez-Chapado, Manuel; Schally, Andrew V; Prieto, Juan C; Carmena, María J

    2012-10-01

    Clear renal cell carcinoma (cRCC) is an aggressive and fatal neoplasm. The present work was undertaken to investigate the antiproliferative potential of vasoactive intestinal peptide (VIP) exposure on non-tumoral (HK2) and tumoral (A498, cRCC) human proximal tubular epithelial cell lines. Reverse transcription and semiquantitative PCR was used at the VIP mRNA level whereas enzyme immunoanalysis was performed at the protein level. Both renal cell lines expressed VIP as well as VIP/pituitary adenylate cyclase-activating peptide (VPAC) receptors whereas only HK2 cells expressed formyl peptide receptor-like 1 (FPRL-1). Receptors were functional, as shown by VIP stimulation of adenylyl cyclase activity. Treatment with 0.1μM VIP (24h) inhibited proliferation of A498 but not HK2 cells as based on a reduction in the incorporation of [(3)H]-thymidine and BrdU (5'-Br-2'-deoxyuridine), PCNA (proliferating-cell nuclear antigen) expression and STAT3 (signal transducer and activator of transcription 3) expression and activation. VPAC(1)-receptor participation was established using JV-1-53 antagonist and siRNA transfection. Growth-inhibitory response to VIP was related to the cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP (EPAC)/phosphoinositide 3-kinase (PI3-K) signaling systems as shown by studies on adenylate cyclase stimulation, and using the EPAC-specific compound 8CPT-2Me-cAMP and specific kinase inhibitors such as H89, wortmannin and PD98059. The efficacy of VIP on the prevention of tumor progression was confirmed in vivo using xenografted athymic mouse. These actions support a potential role of this peptide and its agonists in new therapies for cRCC.

  18. Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4

    Science.gov (United States)

    Allam, Ramanjaneyulu; Scherbaum, Christina Rebecca; Darisipudi, Murthy Narayana; Mulay, Shrikant R.; Hägele, Holger; Lichtnekert, Julia; Hagemann, Jan Henrik; Rupanagudi, Khader Valli; Ryu, Mi; Schwarzenberger, Claudia; Hohenstein, Bernd; Hugo, Christian; Uhl, Bernd; Reichel, Christoph A.; Krombach, Fritz; Monestier, Marc; Liapis, Helen; Moreth, Kristin; Schaefer, Liliana

    2012-01-01

    In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI. PMID:22677551

  19. Cystic papillary renal cell carcinoma arising from an involutional multicystic dysplastic kidney

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Jae; Kim, Bong Soo; Huh, Jung Sik; Park, Kyung Gi; Choi, Guk Myung; Kim, Seung Hyoung; Maeng, Young Hee [Jeju National University School of Medicine, Jeju National University Hospital, Jeju (Korea, Republic of)

    2015-11-15

    Multicystic dysplastic kidney is a common cystic renal disease that often occurs in infancy. Recent studies demonstrate the possibility for spontaneous involution of a dysplastic kidney. In such cases, the prognosis is generally excellent and there is a very low incidence of complications. Complications associated with multicystic dysplastic kidney include pain, infection, hypertension, and neoplasia. Renal cell carcinomas are extremely rare in multicystic dysplastic kidneys. To our knowledge, no case report has described a radiologic finding of renal cell carcinoma arising from an involutional multicystic dysplastic kidney. We report a case of histopathologically validated cystic papillary renal cell carcinoma arising from an involutional multicystic dysplastic kidney and describe its sonographic and CT features.

  20. Concurrent Multilocular Cystic Renal Cell Carcinoma and Leiomyoma in the Same Kidney: Previously Unreported Association

    Directory of Open Access Journals (Sweden)

    Min Su Cheong

    2010-07-01

    Full Text Available We present an unusual case of concurrent occurrence of a multilocular cystic renal cell carcinoma and a leiomyoma in the same kidney of a patient with no evident clinical symptoms. A 38-year-old man was found incidentally to have a cystic right renal mass on computed tomography. Laparoscopic radical nephrectomy was performed under a preoperative diagnosis of cystic renal cell carcinoma. Histology revealed a multilocular cystic renal cell carcinoma and a leiomyoma. This is the first report of this kind of presentation.

  1. Renal cell carcinoma co-existent with other renal disease: clinico-pathological features in pre-dialysis patients and those receiving dialysis or renal transplantation.

    Science.gov (United States)

    Peces, Ramón; Martínez-Ara, Jorge; Miguel, José Luis; Arrieta, Javier; Costero, Olga; Górriz, José Luis; Picazo, Mari-Luz; Fresno, Manuel

    2004-11-01

    Patients on chronic dialysis are prone to developing acquired cystic kidney disease (ACKD), which may lead to the development of renal cell carcinoma (RCC). The risk factors for the development of RCC so far have not been determined in pre-dialysis patients with co-existent renal disease. The aim of this study was to evaluate the clinico-pathological features of RCC in pre-dialysis patients with associated renal diseases or in those undergoing chronic dialysis and renal transplantation. We studied 32 kidneys from 31 patients with RCC and associated renal diseases. Of those, 18 kidneys were from 17 patients not on renal replacement therapy (RRT) when diagnosed with RCC; 14 patients received dialysis or dialysis followed by renal transplantation. Several clinico-pathological features were analysed and compared between the two groups. Overall, there was a preponderance of males (75%); nephrosclerosis was the predominant co-existent disease (31%). The median intervals from renal disease to RCC in the dialysis and transplanted groups were significantly longer than in the pre-dialysis group (15.8+/-1.1 vs 2.4+/-0.7 years, P<0.0001). In contrast to pre-dialysis RCC, the dialysis and transplant RCC groups had greater frequency of ACKD (100 vs 28%, P<0.0001), papillary type RCC (43 vs 11%, P<0.05) and multifocal tumours (43 vs 5%, P<0.05). At the end of the study, 71% of dialysis and transplanted patients and 72% of pre-dialysis patients were alive. ACKD develops in dialysis patients, as it does in those with renal disease prior to RRT. The duration of renal disease, rather than the dialysis procedure itself, appears to be the main determinant of ACKD and RCC. The RCC occurring in patients with ACKD and prolonged RRT is more frequently of the papillary type and multifocal than the RCC occurring in patients with no or few acquired cysts and a short history of renal disease. Long-term outcomes did not differ between the two groups.

  2. Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall'Oglio

    2005-02-01

    Full Text Available INTRODUCTION: Renal cell carcinoma with sarcomatoid differentiation is a tumor with aggressive behavior that is poorly responsive to immunotherapy. The objective of this study is to report our experience in the treatment of 15 patients with this tumor. MATERIALS AND METHODS: We retrospectively analyzed 15 consecutive cases of renal cell carcinoma with sarcomatoid differentiation diagnosed between 1991 and 2003. The clinical presentation and the pathological stage were assessed, as were the tumor's pathological features, use of adjuvant immunotherapy and survival. The study's primary end-point was to assess survival of these individuals. RESULTS: The sample included 8 women and 7 men with mean age of 63 years (44 - 80; follow-up ranged from 1 to 100 months (mean 34. Upon presentation, 87% were symptomatic and 4 individuals had metastatic disease. Mean tumor size was 9.5 cm (4 - 24 with the following pathological stages: 7% pT1, 7% pT2, 33% pT3, and 53% pT4. The pathological features showed high-grade tumors with tumoral necrosis in 87% of the lesions and 80% of intratumoral microvascular invasion. Disease-free and cancer-specific survival rates were 40 and 46% respectively, with 2 cases responding to adjuvant immunotherapy. CONCLUSIONS: Patients with sarcomatoid tumors of the kidney have a low life expectancy, and sometimes surgical resection associated with immunotherapy can lead to a long-lasting therapeutic response.

  3. The prospect of precision therapy for renal cell carcinoma.

    Science.gov (United States)

    Ciccarese, Chiara; Brunelli, Matteo; Montironi, Rodolfo; Fiorentino, Michelangelo; Iacovelli, Roberto; Heng, Daniel; Tortora, Giampaolo; Massari, Francesco

    2016-09-01

    The therapeutic landscape of renal cell carcinoma (RCC) has greatly expanded in the last decade. From being a malignancy orphan of effective therapies, kidney cancer has become today a tumor with several treatment options. Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). In this complex scenario it is important to find prognostic and predictive factors that can help in decision making in the treatment of mRCC.

  4. The role of glutathione transferases in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ćorić Vesna

    2016-01-01

    Full Text Available Mounting evidence suggest that members of the subfamily of cytosolic glutathione S-transferases (GSTs possess roles far beyond the classical glutathione-dependent enzymatic conjugation of electrophilic metabolites and xenobiotics. Namely, monomeric forms of certain GSTs are capable of forming protein: protein interactions with protein kinases and regulate cell apoptotic pathways. Due to this dual functionality of cytosolic GSTs, they might be implicated in both the development and the progression of renal cell carcinoma (RCC. Prominent genetic heterogeneity, resulting from the gene deletions, as well as from SNPs in the coding and non-coding regions of GST genes, might affect GST isoenzyme profiles in renal parenchyma and therefore serve as a valuable indicator for predicting the risk of cancer development. Namely, GSTs are involved in the biotransformation of several compounds recognized as risk factors for RCC. The most potent carcinogen of polycyclic aromatic hydrocarbon diol epoxides, present in cigarette smoke, is of benzo(apyrene (BPDE, detoxified by GSTs. So far, the relationship between GST genotype and BPDE-DNA adduct formation, in determining the risk for RCC, has not been evaluated in patients with RCC. Although the association between certain individual and combined GST genotypes and RCC risk has been debated in a the literature, the data on the prognostic value of GST polymorphism in patients with RCC are scarce, probably due to the fact that the molecular mechanism supporting the role of GSTs in RCC progression has not been clarified as yet.

  5. Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss

    Directory of Open Access Journals (Sweden)

    Mohammed Mahdi Althaf

    2016-01-01

    Full Text Available The incidence of renal cell carcinomas (RCCs in renal transplant recipients is reported as 1.1-1.5% in the native kidneys and 0.22-0.25% in the renal allograft. There are no data to support routine surveillance for tumors in transplant recipients. Most reported cases of RCCs occurring in renal allografts were incidental findings in asymptomatic patients. Herein, we report the second case of lone chromophobe RCC (ChRCC of the renal allograft presenting with weight loss. Loss of weight is a presenting symptom in one-third of ChRCCs occurring in the native kidneys in the general population. Based on the age of the patient, R.E.N.A.L nephrometry score of the tumor and the lack of data on the prognosis of this histological subtype in a climate of long-term immunosuppression, we elected for radical nephrectomy. We suggest that RCCs should be considered in the differential diagnosis of a transplant recipient presenting with weight loss even in the absence of localizing symptoms or signs.

  6. Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss.

    Science.gov (United States)

    Althaf, Mohammed Mahdi; Al-Sunaid, Mohammed S; Abdelsalam, Mohamed Said; Alkorbi, Lutfi A; Al-Hussain, Turki O; Dababo, Mohammed Anas; Haq, Naveed

    2016-01-01

    The incidence of renal cell carcinomas (RCCs) in renal transplant recipients is reported as 1.1-1.5% in the native kidneys and 0.22-0.25% in the renal allograft. There are no data to support routine surveillance for tumors in transplant recipients. Most reported cases of RCCs occurring in renal allografts were incidental findings in asymptomatic patients. Herein, we report the second case of lone chromophobe RCC (ChRCC) of the renal allograft presenting with weight loss. Loss of weight is a presenting symptom in one-third of ChRCCs occurring in the native kidneys in the general population. Based on the age of the patient, R.E.N.A.L nephrometry score of the tumor and the lack of data on the prognosis of this histological subtype in a climate of long-term immunosuppression, we elected for radical nephrectomy. We suggest that RCCs should be considered in the differential diagnosis of a transplant recipient presenting with weight loss even in the absence of localizing symptoms or signs.

  7. Isolation, growth, and characterization of human renal epithelial cells using traditional and 3D methods.

    Science.gov (United States)

    Gildea, John J; McGrath, Helen E; Van Sciver, Robert E; Wang, Dora Bigler; Felder, Robin A

    2013-01-01

    The kidney is a highly heterogeneous organ that is responsible for fluid and electrolyte balance. Much interest is focused on determining the function of specific renal epithelial cells in humans, which can only be accomplished through the isolation and growth of nephron segment-specific epithelial cells. However, human renal epithelial cells are notoriously difficult to maintain in culture. This chapter describes the isolation, growth, immortalization, and characterization of the human renal proximal tubule cell. In addition, we describe new paradigms in 3D cell culture which allow the cells to maintain more in vivo-like morphology and function.

  8. Single metastatic renal cell carcinoma in gallbladder: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Young; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Yi, Kyung Sik; Park, Kil Sun; Sung, Ro Hyun [Chungbuk National Univ. Hospital, Cheongju (Korea, Republic of)

    2012-07-15

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancy. 25% to 57% of RCC patients exhibit overt evidence of metastatic disease at initial presentation. Metastases to the gallbladder is uncommon and usually detected in only 0.4-0.6% of autopsies. We report the case of a 58 year old man who presented with a metastasis in the gallbladder from RCC. He had undergone went a right nephrectomy four years ago. There was no evidence of metastasis. A follow up abdomen CT scan taken three years after operation showed a polypoid lesion within the gallbladder. The size of the polypoid lesion had increased at the follow up CT and the enhancement pattern of lesion became similar to that of RCC. A Cholecystectomy was performed. Histopathological examination revealed the polyp was clear cell carcinoma of metastatic origin from kidney.

  9. Automated grading of renal cell carcinoma using whole slide imaging

    Directory of Open Access Journals (Sweden)

    Fang-Cheng Yeh

    2014-01-01

    Full Text Available Introduction: Recent technology developments have demonstrated the benefit of using whole slide imaging (WSI in computer-aided diagnosis. In this paper, we explore the feasibility of using automatic WSI analysis to assist grading of clear cell renal cell carcinoma (RCC, which is a manual task traditionally performed by pathologists. Materials and Methods: Automatic WSI analysis was applied to 39 hematoxylin and eosin-stained digitized slides of clear cell RCC with varying grades. Kernel regression was used to estimate the spatial distribution of nuclear size across the entire slides. The analysis results were correlated with Fuhrman nuclear grades determined by pathologists. Results: The spatial distribution of nuclear size provided a panoramic view of the tissue sections. The distribution images facilitated locating regions of interest, such as high-grade regions and areas with necrosis. The statistical analysis showed that the maximum nuclear size was significantly different (P < 0.001 between low-grade (Grades I and II and high-grade tumors (Grades III and IV. The receiver operating characteristics analysis showed that the maximum nuclear size distinguished high-grade and low-grade tumors with a false positive rate of 0.2 and a true positive rate of 1.0. The area under the curve is 0.97. Conclusion: The automatic WSI analysis allows pathologists to see the spatial distribution of nuclei size inside the tumors. The maximum nuclear size can also be used to differentiate low-grade and high-grade clear cell RCC with good sensitivity and specificity. These data suggest that automatic WSI analysis may facilitate pathologic grading of renal tumors and reduce variability encountered with manual grading.

  10. Long-term follow-up of kidney allografts in patients with sickle cell hemoglobinopathy Transplante renal na anemia falciforme

    OpenAIRE

    Friedrisch,João R.; Barros, Elvino J.; Roberto C. Manfro; Bittar,Cristhina M.; Silla,Lúcia M. R.

    2003-01-01

    Although sickle cell anemia and sickle cell disease produce a variety of functional renal abnormalities they uncommonly cause end stage renal failure. Renal transplantation has been a successful alternative for the treatment of the rare terminal chronic renal failure with outcomes comparable with non-sickle recipients. This approach, however, has not been often described on patients with renal failure associated with SC hemoglobinopathy. Here we report the outcomes of two patients with chroni...

  11. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy

    DEFF Research Database (Denmark)

    Ravaud, Alain; Motzer, Robert J; Pandha, Hardev S

    2016-01-01

    BACKGROUND Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephr...

  12. Association of dyslipidemia with renal cell carcinoma: a 1∶2 matched case-control study.

    Directory of Open Access Journals (Sweden)

    Chunfang Zhang

    Full Text Available Abnormal serum lipid profiles are associated with the risk of some cancers, but the direction and magnitude of the association with renal cell carcinoma is unclear. We explore the relationship between serum lipids and renal cell carcinoma via a matched case-control study. A 1∶2-matched case-control study design was applied, where one renal cell carcinoma patient was matched to two non-renal-cell-carcinoma residents with respect to age (±0 year and gender. Cases (n = 248 were inpatients with a primary diagnosis of renal cell carcinoma, confirmed by pathology after operations. Controls were sampled from a community survey database matched on age and gender with cases, 2 controls for each case. Stratified Cox proportional hazard regression analysis was used to obtain hazard ratios and corresponding 95% confidence intervals of lipids level and dyslipidemia for the risk of renal cell carcinoma. Elevated serum cholesterol (p<0.001, LDL cholesterol (p<0.001, and HDL cholesterol (p = 0.003 are associated with decreased hazard of renal cell carcinoma, adjusting for obesity, smoke, hypertension and diabetes. However, risk caused by hTG showed no statistical significance (p = 0.263. This study indicates that abnormal lipid profile influences the risk of renal cell carcinoma.

  13. Renal cell carcinoma in an ectopic pelvic kidney in a patient presenting with acute urinary retention

    Directory of Open Access Journals (Sweden)

    Isabella Dash

    2010-12-01

    Full Text Available The incidence of renal cell carcinoma in a pelvic kidney is rare, and has only been described in a very small number of cases. We describe a case where an incidental ectopic kidney with invasive renal cell carcinoma was diagnosed during a separate emergency admission for acute urinary retention.

  14. Insulin-like growth factor-1 sustains stem cell mediated renal repair.

    NARCIS (Netherlands)

    Imberti, B.; Morigi, M.; Tomasoni, S.; Rota, C.; Corna, D.; Longaretti, L.; Rottoli, D.; Valsecchi, F.; Benigni, A.; Wang, J.; Abbate, M.; Zoja, C.; Remuzzi, G.

    2007-01-01

    In mice with cisplatin-induced acute kidney injury, administration of bone marrow-derived mesenchymal stem cells (MSC) restores renal tubular structure and improves renal function, but the underlying mechanism is unclear. Here, we examined the process of kidney cell repair in co-culture experiments

  15. Transduction of interleukin-10 through renal artery attenuates vascular neointimal proliferation and infiltration of immune cells in rat renal allograft.

    Science.gov (United States)

    Xie, Jingxin; Li, Xueyi; Meng, Dan; Liang, Qiujuan; Wang, Xinhong; Wang, Li; Wang, Rui; Xiang, Meng; Chen, Sifeng

    2016-08-01

    Renal transplantation is the treatment of choice for end-stage renal failure. Although acute rejection is not a major issue anymore, chronic rejection, especially vascular rejection, is still a major factor that might lead to allograft dysfunction on the long term. The role of the local immune-regulating cytokine interleukin-10 (IL-10) in chronic renal allograft is unclear. Many clinical observations showed that local IL-10 level was negatively related to kidney allograft function. It is unknown this negative relationship was the result of immunostimulatory property or insufficient immunosuppression property of local IL-10. We performed ex vivo transduction before transplantation through artery of the renal allograft using adeno-associated viral vectors carrying IL-10 gene. Twelve weeks after transplantation, we found intrarenal IL-10 gene transduction significantly inhibited arterial neointimal proliferation, the number of occluded intrarenal artery, interstitial fibrosis, peritubular capillary congestion and glomerular inflammation in renal allografts compared to control allografts receiving PBS or vectors carrying YFP. IL-10 transduction increased serum IL-10 level at 4 weeks but not at 8 and 12 weeks. Renal IL-10 level increased while serum creatinine decreased significantly in IL-10 group at 12 weeks compared to PBS or YFP controls. Immunohistochemical staining showed unchanged total T cells (CD3) and B cells (CD45R/B220), decreased cytotoxic T cells (CD8), macrophages (CD68) and increased CD4+ and FoxP3+ cells in IL-10 group. In summary, intrarenal IL-10 inhibited the allograft rejection while modulated immune response.

  16. Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

    Directory of Open Access Journals (Sweden)

    Thomas C. Wehler

    2008-01-01

    Full Text Available Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P=.039, tumor dedifferentiation (P = .0005, and low hemoglobin (P = .039. In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma.

  17. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer.

    Science.gov (United States)

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-12-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormalities arising in the setting of known renal cell carcinoma, particularly late in the course of disease. This is frequently associated with internal jugular vein thrombi, which should be evaluated with an abnormal thyroid. Thyroglobulin levels are usually normal in such patients.

  18. Relationship of Serum Interleukin-18 and Interleukin-12 Levels with Clinicopathology in Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    NONG Shao-jun; WEN Duan-gai; FAN Cai-bin; OUYANG Jun

    2007-01-01

    Objective: To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods: Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results: Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers (P<0.05) and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels (P<0.05). In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion: Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.

  19. Imaging findings of common benign renal tumors in the era of small renal masses: Differential diagnosis from small renal cell carcinoma: Current status and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sung Min; Cho, Jeong Yeon [Dept. of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-02-15

    The prevalence of small renal masses (SRM) has risen, paralleling the increased usage of cross-sectional imaging. A large proportion of these SRMs are not malignant, and do not require invasive treatment such as nephrectomy. Therefore, differentation between early renal cell carcinoma (RCC) and benign SRM is critical to achieve proper management. This article reviews the radiological features of benign SRMs, with focus on two of the most common benign entities, angiomyolipoma and oncocytoma, in terms of their common imaging findings and differential features from RCC. Furthermore, the role of percutaneous biopsy is discussed as imaging is yet imperfect, therefore necessitating biopsy in certain circumstances to confirm the benignity of SRMs.

  20. Differences between renal effects of venom from two Bothrops jararaca populations from southeastern and southern Brazil.

    Science.gov (United States)

    Jorge, Roberta Jeane Bezerra; Jorge, Antônio Rafael Coelho; de Menezes, Ramon Róseo Paula Pessoa Bezerra; Mello, Clarissa Perdigão; Lima, Danya Bandeira; Silveira, João Alison de Moraes; Alves, Natacha Teresa Queiroz; Marinho, Aline Diogo; Ximenes, Rafael Matos; Corrêa-Netto, Carlos; Gonçalves Machado, Larissa; Zingali, Russolina Benedeta; Martins, Alice Maria Costa; Monteiro, Helena Serra Azul

    2017-01-01

    Components from animal venoms may vary according to the snake's age, gender and region of origin. Recently, we performed a proteomic analysis of Bothrops jararaca venom from southern (BjSv) and southeastern (BjSEv) Brazil, showing differences in the venom composition, as well as its biological activity. To continue the study, we report in this short communication the different effects induced by the BjSEv and BjSv on isolated kidney and MDCK renal cells. BjSEv decreased perfusion pressure (PP) and renal vascular resistance (RVR) and increased urinary flow (UF) and glomerular filtration rate (GFR), while BjSv did not alter PP and RVR and reduced UF and GFR. Both types of venom, more expressively BjSEv, reduced %TNa(+), %TK(+) and %Cl(-). In MDCK cells, the two types of venom showed cytotoxicity with IC50 of 1.22 μg/mL for BjSv and 1.18 μg/mL for BjSEv and caused different profiles of cell death, with BjSv being more necrotic. In conclusion, we suggest that BjSv is more nephrotoxic than BjSEv. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Tuberous sclerosis with bilateral renal cell carcinoma in a child: A case report

    Directory of Open Access Journals (Sweden)

    Sanjay Choudhuri

    2015-01-01

    Full Text Available Tuberous sclerosis complex (TCS is an autosomal dominant disease which comes under a group of diseases known as neurocutaneous syndrome. Incidence of TCS is around 1 in 6000. The clinical triad of papular facial nevus, seizures and mental retardation is found in less than 50% of the patients. Renal lesions in TCS commonly consist of simple renal cyst and angiomyolipomas. Renal cell carcinoma though rarely associated with tuberous sclerosis may be its significant manifestations. We report a case of TCS with bilateral renal cell carcinoma in a 12 year old child with classical radiological and clinical signs.

  2. Radiofrequency Ablation Treatment for Renal Cell Carcinoma: Early Clinical Experience

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seong Hoon; Yoon, Seong Kuk; Cho, Jin Han; Oh, Jong Young; Nam, Kyung Jin; Kwon, Hee Jin; Kim, Su Yeon; Kang, Myong Jin; Choi, Sun Seob; Sung, Gyung Tak [Dong-A University College of Medicine, Busan (Korea, Republic of)

    2008-08-15

    To evaluate the early clinical experience associated with radiofrequency (RF) ablation in patients with renal cell carcinoma (RCC). The RF ablation treatment was performed on 17 tumors from 16 patients (mean age, 60.5 years; range, 43 73 years) with RCC. The treatment indications were localized, solid renal mass, comorbidities, high operation risk, and refusal to perform surgery. All tumors were treated by a percutaneous CT (n = 10), followed by an US-guided (n = 2), laparoscopy-assisted US (n = 2), and an open (n = 2) RF ablation. Furthermore, patients underwent a follow- up CT at one day, one week, one month, three and six months, and then every six months from the onset of treatment. We evaluated the technical success, technical effectiveness, ablation zone, benign periablation enhancement, irregular peripheral enhancement, and complications. All 17 exophytic tumors (mean size, 2.2 cm; range, 1.1 5.0 cm) were completely ablated. Technical success and effectiveness was achieved in all cases and the mean follow-up period was 23.8 months (range, 17 33 months). A local recurrence was not detected in any of the cases; however, five patients developed complications as a result of treatment, including hematuria (n = 2), mild thermal injury of the psoas muscle (n = 1), mild hydronephrosis (n = 1), and fistula formation (n = 1). The RF ablation is an alternative treatment for exophytic RCCs and represents a promising treatment for some patients with small RCCs.

  3. Renal dysfunction in patients with sickle cell anemia or sickle cell trait

    Directory of Open Access Journals (Sweden)

    R. Sesso

    1998-10-01

    Full Text Available Patients with sickle cell anemia (Hb SS or sickle cell trait (Hb AS may present several types of renal dysfunction; however, comparison of the prevalence of these abnormalities between these two groups and correlation with the duration of disease in a large number of patients have not been thoroughly investigated. In a cross-sectional study using immunoenzymometric assays to measure tubular proteinuria, microalbuminuria, measurement of creatinine clearance, urinary osmolality and analysis of urine sediment, we evaluated glomerular and tubular renal function in 106 adults and children with Hb SS (N = 66 or Hb AS (N = 40 with no renal failure (glomerular filtration rate (GFR >85 ml/min. The percentage of individuals with microalbuminuria was higher among Hb SS than among Hb AS patients (30 vs 8%, P85 ml/min.

  4. Sunitinib activates Axl signaling in renal cell cancer.

    Science.gov (United States)

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies.

  5. End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells

    NARCIS (Netherlands)

    Westerweel, Peter E; Hoefer, Imo E; Blankestijn, Peter J; de Bree, Petra; Groeneveld, Dafna; van Oostrom, Olivia; Braam, Branko; Koomans, Hein A; Verhaar, Marianne C

    2007-01-01

    Patients with end-stage renal disease (ESRD) on hemodialysis have an increased risk of cardiovascular disease (CVD). Circulating endothelial progenitor cells (EPC) contribute to vascular regeneration and repair, thereby protecting against CVD. However, circulating smooth muscle progenitor cells (SPC

  6. Enhanced propagation of adult human renal epithelial progenitor cells to improve cell sourcing for tissue-engineered therapeutic devices for renal diseases.

    Science.gov (United States)

    Westover, Angela J; Buffington, Deborah A; Humes, H D

    2012-08-01

    Renal cell therapy employing cells derived from adult renal epithelial cell (REC) progenitors promises to reduce the morbidity of patients with renal insufficiency due to acute renal failure and end stage renal disease. To this end, tissue engineered devices addressing the neglected biologic component of renal replacement therapy are being developed. Because human donor tissue is limited, novel enhanced progenitor cell propagation (EP) techniques have been developed and applied to adult human kidney transplant discards from six donors. Changes include more efficient digestion and the amplification of progenitors prior to terminal epithelial differentiation promoted by contact inhibition and the addition of retinoic acid. Differentiated morphology in EP populations was demonstrated by the ability to form polarized epithelium with tight junctions, apical central cilia and expression of brush border membrane enzymes. Evaluation of lipopolysaccharide stimulated interleukin-8 secretion and γ-glutamyl transpeptisade activity in EP derived cells was used to confirm therapeutic equivalence to REC obtained using published techniques, which have previously shown efficacy in large animal models and clinical trials. Yield exceeded 10(16) cells/gram cortex from the only kidney obtained due to an anatomical defect, while the average yield from diseased kidneys ranged from 1.1 × 10(9) to 8.8 × 10(11) cells/gram cortex, representing an increase of more than 10 doublings over standard methods. Application of the EP protocol to REC expansion has solved the problem of cell sourcing as the limiting factor to the manufacture of cell based therapies targeting renal diseases and may provide a method for autologous device fabrication from core kidney biopsies. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in acute renal failure.

    Science.gov (United States)

    Ohnishi, Hiroyuki; Mizuno, Shinya; Nakamura, Toshikazu

    2008-02-01

    During the progression of acute renal failure (ARF), the renal tubular S3 segment is sensitive to ischemic stresses. For reversing tubular damage, resident tubular cells proliferate, and bone marrow-derived cells (BMDC) can be engrafted into injured tubules. However, how resident epithelium or BMDC are involved in tubular repair remains unknown. Using a mouse model of ARF, we examined whether hepatocyte growth factor (HGF) regulates a balance of resident cell proliferation and BMDC recruitment. Within 48 h post-renal ischemia, tubular destruction became evident, followed by two-waved regenerative events: 1) tubular cell proliferation between 2 and 4 days, along with an increase in blood HGF; and 2) appearance of BMDC in the tubules from 6 days postischemia. When anti-HGF IgG was injected in the earlier stage, tubular cell proliferation was inhibited, leading to an increase in BMDC in renal tubules. Under the HGF-neutralized state, stromal cell-derived factor-1 (SDF1) levels increased in renal tubules, associated with the enhanced hypoxia. Administrations of anti-SDF1 receptor IgG into ARF mice reduced the number of BMDC in interstitium and tubules. Thus possible cascades include 1) inhibition of tubular cell proliferation by neutralizing HGF leads to renal hypoxia and SDF1 upregulation; and 2) BMDC are eventually engrafted in tubules through SDF1-mediated chemotaxis. Inversely, administration of recombinant HGF suppressed the renal hypoxia, SDF1 upregulation, and BMDC engraftment in ARF mice by enhancing resident tubular cell proliferation. Thus we conclude that HGF is a positive regulator for eliciting resident tubular cell proliferation, and SDF1 for BMDC engraftment during the repair process of ARF.

  8. Cell cycle progression score predicts metastatic progression of clear cell renal cell carcinoma after resection.

    Science.gov (United States)

    Askeland, Eric J; Chehval, Vincent A; Askeland, Ryan W; Fosso, Placede G; Sangale, Zaina; Xu, Nafei; Rajamani, Saradha; Stone, Steven; Brown, James A

    2015-01-01

    The outcome of surgically resected, apparently localized, clear cell renal carcinoma (ccRCC) is uncertain. To evaluate if cell cycle progression (CCP) gene expression can predict future metastasis. Pathologic T2a-T3b tumors at University of Iowa were reviewed. Patients with known or suspected metastasis, lymph node involvement or who received neoadjuvant or adjuvant radiation, chemotherapy or immunotherapy were excluded. Case and control cohorts were defined as those who did or did not develop metastatic disease within 5 years. Measured levels of 31 cell cycle genes and 15 control genes from the tumor were calculated as a CCP score. Additionally, gene expression data for a separate ccRCC cohort was downloaded from The Cancer Genome Atlas (TCGA). Univariate analysis of 26 cases and 38 controls revealed that the CCP score predicted progression to metastasis (OR 2.65, p = 0.0091). In multivariate logistic regression modeling, CCP expression remained a significant independent predictor for progression (p = 0.026). The CCP score was also significantly associated with distant metastasis in the TCGA renal cancer cohort in both univariate (p = 1.0 × 10-9) and multivariate (p = 5.6 × 10-3) analysis. The CCP score has prognostic value in predicting metastatic progression after resection of organ-confined ccRCC.

  9. Tuberous sclerosis with bilateral renal cell carcinoma in a child: A case report

    OpenAIRE

    Sanjay Choudhuri; Jeevanjyoti Mishra; Gyan Prakash Singh; Datteswar Hota

    2015-01-01

    Tuberous sclerosis complex (TCS) is an autosomal dominant disease which comes under a group of diseases known as neurocutaneous syndrome. Incidence of TCS is around 1 in 6000. The clinical triad of papular facial nevus, seizures and mental retardation is found in less than 50% of the patients. Renal lesions in TCS commonly consist of simple renal cyst and angiomyolipomas. Renal cell carcinoma though rarely associated with tuberous sclerosis may be its significant manifestations. We report a c...

  10. Renal Abnormalities in Patients with Sickle Cell Disease: A Single Center Report from Saudi Arabia

    OpenAIRE

    Aleem Aamer

    2008-01-01

    Patients with sickle cell disease (SCD) are at increased risk of serious morbidity and mortality. Renal abnormalities in SCD are well known but renal involvement in Saudi patients with SCD has not been studied. We sought to identify renal abnormalities in adolescent and adult Saudi patients with SCD. We prospectively studied 73 patients with SCD followed up at King Khalid University Hospital, Riyadh, Saudi Arabia from July 2005 to November 2006,. All patients underwent evaluation of kidney fu...

  11. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

    Directory of Open Access Journals (Sweden)

    Victor D. Liou

    2015-01-01

    Full Text Available Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC which metastasized to the base of his penis within 1 month of symptom onset. We also discuss the possible route of metastasis based on primary tumor size and location within the retroperitoneum.

  12. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis.

    Science.gov (United States)

    Liou, Victor D; Darwish, Oussama M; Henry, Mary M; Jun, Ik C; Siddiqui, Sameer A

    2015-01-01

    Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC) to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC which metastasized to the base of his penis within 1 month of symptom onset. We also discuss the possible route of metastasis based on primary tumor size and location within the retroperitoneum.

  13. Serum and Urine Biomarkers for Human Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. L. Pastore

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called “targeted therapies.” The identification of molecular markers in body fluids (e.g., sera and urine, which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients.

  14. Perfluorooctanesulfonate Mediates Renal Tubular Cell Apoptosis through PPARgamma Inactivation.

    Directory of Open Access Journals (Sweden)

    Li-Li Wen

    Full Text Available Perfluorinated chemicals (PFCs are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs. In addition, PFOS increased transcription of inflammatory cytokines (i.e., TNFα, ICAM1, and MCP1 by NFκB activation. Conversely, PFOS reduced the mRNA levels of antioxidative enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase, as a result of reduced PPARγ transactivational activity by using reporter and chromatin immuoprecipitation (ChIP assays. PFOS reduced the protein interaction between PPARγ and PPARγ coactivator-1 alpha (PGC1α by PPARγ deacetylation through Sirt1 upregulation, of which the binding of PPARγ and PGC1α to a peroxisome proliferator response element (PPRE in the promoter regions of these antioxidative enzymes was alleviated in the ChIP assay. Furthermore, Sirt1 also deacetylated p53 and then increased the binding of p53 to Bax, resulting in increased cytosolic cytochrome C. The effect of PPARγ inactivation by PFOS was validated using the PPARγ antagonist GW9662, whereas the adverse effects of PFOS were prevented by PPARγ overexpression and activators, rosiglitozone and L-carnitine, in RTCs. The in vitro finding of protective effect of L-carnitine was substantiated in vivo using Balb/c mice model subjected to PFOS challenge. Altogether, we provide in vivo and in vitro evidence for the protective mechanism of L-carnitine in eliminating PFOS-mediated renal injury, at least partially, through PPARγ activation.

  15. Update on vaccine development for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Nina Chi

    2010-08-01

    Full Text Available Nina Chi1, Jodi K Maranchie2,3, Leonard J Appleman3,4, Walter J Storkus1,3,51Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 2Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 3University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States; 4Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 5Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAAbstract: Renal cell carcinoma (RCC remains a significant health concern that frequently presents as metastatic disease at the time of initial diagnosis. Current first-line therapeutics for the advanced-stage RCC include antiangiogenic drugs that have yielded high rates of objective clinical response; however, these tend to be transient in nature, with many patients becoming refractory to chronic treatment with these agents. Adjuvant immunotherapies remain viable candidates to sustain disease-free and overall patient survival. In particular, vaccines designed to optimize the activation, maintenance, and recruitment of specific immunity within or into the tumor site continue to evolve. Based on the integration of increasingly refined immunomonitoring systems in both translational models and clinical trials, allowing for the improved understanding of treatment mechanism(s of action, further refined (combinational vaccine protocols are currently being developed and evaluated. This review provides a brief history of RCC vaccine development, discusses the successes and limitations in such approaches, and provides a rationale for developing combinational vaccine approaches that may provide improved clinical benefits to patients with RCC.Keywords: renal cell carcinoma, vaccines, immunotherapy, combinational therapy, cellular immunity

  16. Tivozanib in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hepgur M

    2013-06-01

    Full Text Available Mehmet Hepgur, Sarmad Sadeghi, Tanya B Dorff, David I Quinn Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA Abstract: Renal cell carcinoma (RCC is an aggressive malignancy compared to other urological malignancies and has been associated with poor responses to conventional cytotoxic chemotherapy. Interferon-a and interleukin-2 were previously utilized in a limited number of patients with good performance status due to toxicity and safety issues. Over the last decade, through advances in the understanding of the biology and pathology of RCC, the important role of vascular endothelial growth factor (VEGF in RCC has been identified. Data from randomized trials have led to the approval of first-generation tyrosine kinase inhibitors (TKIs sorafenib, sunitinib, and pazopanib; however, these agents inhibit a wide variety of kinase targets and are associated with a range of adverse effects. More recently, a new generation TKI, axitinib, has been approved by the US Food and Drug Administration. Tivozanib is a novel TKI, which is a potent inhibitor of VEGF-1, VEGF-2, VEGF-3, c-kit, and PDGR kinases, with a more restricted target spectrum. Phase II and III studies have demonstrated significant activity and a favorable safety profile as an initial targeted treatment for advanced RCC. This review examines the emerging data with tivozanib for the treatment of advanced RCC. Preclinical investigations as well as Phase I, II, and III data are examined; data on the comparative benefits of tivozanib are reviewed. Finally, we discuss the future potential of tivozanib in combination, biomarkers associated with tivozanib response, and acquisition of resistance and nonkidney cancer indications. Keywords: targeted therapy, renal cell cancer, tyrosine kinase inhibitor, tivozanib

  17. An association between overexpression of DNA methyltransferase 3B4 and clear cell renal cell carcinoma.

    Science.gov (United States)

    Liu, You; Sun, Liantao; Fong, Peter; Yang, Jie; Zhang, Zhuxia; Yin, Shuihui; Jiang, Shuyuan; Liu, Xiaolei; Ju, Hongge; Huang, Lihua; Bai, Jing; Gong, Kerui; Yan, Shaochun; Zhang, Chunyang; Shao, Guo

    2017-02-01

    It is well known that abnormal DNA methylations occur frequently in kidney cancer. However, it remains unclear exactly which types of DNA methyltransferases (DNMT) contribute to the pathologies of kidney cancers. In order to determine the functions of DNA methyltransferase in kidney tumorigenesis on the molecular level, we examined the mRNA expression levels of DNMT1, DNMT3A, DNMT3B, and DNMT3B variants in renal cell carcinoma tissue. Both mRNA and protein levels of DNMT3B4, a splice variant of DNMT3B, were increased in renal cell carcinoma tissue compared with adjacent control tissues. Additionally, Alu elements and long interspersed nuclear elements (LINE-1) were hypomethylated in renal cell carcinoma tissue. Meanwhile, methylation of the promoter for RASSF1A, a tumor suppressor gene, was moderately increased in renal cell carcinoma tissue, while RASSF1A expression was decreased. Thus, our data suggest that the overexpression of DNMT3B4 may play an important role in human kidney tumorigenesis through chromosomal instability and methylation of RASSF1A.

  18. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    Science.gov (United States)

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

    2011-07-01

    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.

  19. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

    Science.gov (United States)

    Toyohara, Takafumi; Mae, Shin-Ichi; Sueta, Shin-Ichi; Inoue, Tatsuyuki; Yamagishi, Yukiko; Kawamoto, Tatsuya; Kasahara, Tomoko; Hoshina, Azusa; Toyoda, Taro; Tanaka, Hiromi; Araoka, Toshikazu; Sato-Otsubo, Aiko; Takahashi, Kazutoshi; Sato, Yasunori; Yamaji, Noboru; Ogawa, Seishi; Yamanaka, Shinya

    2015-01-01

    Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, the development of regenerative therapies using human induced pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for AKI. We describe our methodology for generating renal progenitors from hiPSCs that show potential in ameliorating AKI. We established a multistep differentiation protocol for inducing hiPSCs into OSR1+SIX2+ renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro and in vivo. Moreover, we found that renal subcapsular transplantation of hiPSC-derived renal progenitors ameliorated the AKI in mice induced by ischemia/reperfusion injury, significantly suppressing the elevation of blood urea nitrogen and serum creatinine levels and attenuating histopathological changes, such as tubular necrosis, tubule dilatation with casts, and interstitial fibrosis. To our knowledge, few reports demonstrating the therapeutic efficacy of cell therapy with renal lineage cells generated from hiPSCs have been published. Our results suggest that regenerative medicine strategies for kidney diseases could be developed using hiPSC-derived renal cells. Significance This report is the first to demonstrate that the transplantation of renal progenitor cells differentiated from human induced pluripotent stem (iPS) cells has therapeutic effectiveness in mouse models of acute kidney injury induced by ischemia/reperfusion injury. In addition, this report clearly demonstrates that the therapeutic benefits come from trophic effects by the renal progenitor cells, and it identifies the renoprotective factors secreted by the progenitors. The results of this study indicate the feasibility of developing regenerative medicine strategy using iPS cells against renal diseases

  20. Renal Cell Carcinoma of the Kidney with Synchronous Ipsilateral Transitional Cell Carcinoma of the Renal Pelvis

    Directory of Open Access Journals (Sweden)

    Dogan Atilgan

    2013-01-01

    Full Text Available A 73-year-old man was admitted to our clinic with flank pain and gross macroscopic hematuria. Radiologic examination revealed a solid mass in the left kidney and additionally another mass in the ureteropelvic junction of the same kidney with severe hydronephrosis. Left nephroureterectomy with bladder cuff removel was performed, and histopathological evolution showed a Fuhrman grade 3 clear cell type RCC with low-grade TCC of the pelvis.

  1. Remanent cell traction force in renal vascular smooth muscle cells induced by integrin-mediated mechanotransduction.

    Science.gov (United States)

    Balasubramanian, Lavanya; Lo, Chun-Min; Sham, James S K; Yip, Kay-Pong

    2013-02-15

    It was previously demonstrated in isolated renal vascular smooth muscle cells (VSMCs) that integrin-mediated mechanotransduction triggers intracellular Ca(2+) mobilization, which is the hallmark of myogenic response in VSMCs. To test directly whether integrin-mediated mechanotransduction results in the myogenic response-like behavior in renal VSMCs, cell traction force microscopy was used to monitor cell traction force when the cells were pulled with fibronectin-coated or low density lipoprotein (LDL)-coated paramagnetic beads. LDL-coated beads were used as a control for nonintegrin-mediated mechanotransduction. Pulling with LDL-coated beads increased the cell traction force by 61 ± 12% (9 cells), which returned to the prepull level after the pulling process was terminated. Pulling with noncoated beads had a minimal increase in the cell traction force (12 ± 9%, 8 cells). Pulling with fibronectin-coated beads increased the cell traction force by 56 ± 20% (7 cells). However, the cell traction force was still elevated by 23 ± 14% after the pulling process was terminated. This behavior is analogous to the changes of vascular resistance in pressure-induced myogenic response, in which vascular resistance remains elevated after myogenic constriction. Fibronectin is a native ligand for α(5)β(1)-integrins in VSMCs. Similar remanent cell traction force was found when cells were pulled with beads coated with β(1)-integrin antibody (Ha2/5). Activation of β(1)-integrin with soluble antibody also triggered variations of cell traction force and Ca(2+) mobilization, which were abolished by the Src inhibitor. In conclusion, mechanical force transduced by α(5)β(1)-integrins triggered a myogenic response-like behavior in isolated renal VSMCs.

  2. Adrenal and renal corticomedullary junction iron deposition in red cell aplasia

    Energy Technology Data Exchange (ETDEWEB)

    Rakow-Penner, Rebecca; Vasanawala, Shreyas [Stanford University School of Medicine, Department of Radiology, Stanford, CA (United States); Glader, Bert [Stanford University School of Medicine, Department of Pediatric Hematology and Oncology, Stanford, CA (United States); Yu, Huanzhou [Global MR Applied Science Lab, GE Healthcare, Menlo Park, CA (United States)

    2010-12-15

    Iron deposition can occur in the kidneys as a result of hemolysis or extensive iron overload from transfusions. With T2* MRI, renal iron deposition can be visualized. In this report, renal corticomedullary junction iron deposition is noted using T2* MRI in a boy with red cell aplasia. The renal corticomedullary junction iron deposition is an indication of the severity of his iron overload. This is an unusual finding and brings clinical attention to the boy's renal function for further evaluation. (orig.)

  3. Relationships between oxidative stress markers and red blood cell characteristics in renal azotemic dogs.

    Science.gov (United States)

    Buranakarl, C; Trisiriroj, M; Pondeenana, S; Tungjitpeanpong, T; Jarutakanon, P; Penchome, R

    2009-04-01

    Oxidative stress parameters and erythrocyte characteristics were studied in 15 normal healthy dogs and 33 renal azotaemic dogs from Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University. Dogs with renal azotaemia had reduced mean corpuscular volume (MCV) (PDogs with severe renal azotaemia had higher intraerythrocytic sodium contents (RBC-Na) (Pred blood cell catalase activity and glutathione and plasma malondialdehyde were unaltered while urinary malondialdehyde-creatinine ratio (U-MDA/Cr) increased significantly (Pdogs. Moreover, the U-MDA/Cr is a sensitive biochemical parameter which increased along with degree of renal dysfunction.

  4. Immune reactivity of cells from long-term rat renal allograft survivors

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, A.; Stuart, F.P.; Fitch, F.W.

    1978-11-01

    Lewis rats receiving an LBN kidney allograft demonstrate no signs of rejection if they are pretreated with donor spleen cells and antiserum reactive with the donor alloantigen. We examined the cellular reactivity of long-term kidney allograft survivors. Normal proliferative and cytolytic responses were obtained with spleen cells from long-term survivors, in marked contrast to the diminished responses of cells from neonatally tolerant rats or the heightened cytolytic response of cells from rats that had rejected a renal allograft. Serum from long-term renal allograft survivors as well as serum obtained from rats at the time of transplantation did not suppress proliferative or cytolytic responses of normal cells. The results of this study suggest that long-term renal allograft survivors possess the precursors of those cells which are responsible for proliferative and cytolytic responses in mixed leukocyte cultures, but that they have not been sensitized to their renal allograft.

  5. Renal T-cell lymphoma with cerebral metastasis in a dog with chronic canine ehrlichiosis

    Directory of Open Access Journals (Sweden)

    E.P. Lane

    2002-07-01

    Full Text Available A renal T-cell lymphoma with exclusive cerebral metastasis was diagnosed in a 5-year-old Staffordshire bull terrier bitch euthanased for aggression. This is the first recorded case of primary renal lymphoma in a dog. Immune suppression, due to chronic canine monocytic ehrlichiosis, mayaccount for the unusual primary site and metastatic patternof the tumour.

  6. Renal adenocarcinoma, hepatocellular carcinoma, and pancreatic islet cell carcinoma in a binturong (Arctictis binturong).

    Science.gov (United States)

    Klaphake, Eric; Shoieb, Ahmed; Ramsay, Ed; Schumacher, Juergen; Craig, Linden

    2005-03-01

    A 19-yr-old binturong (Arctictis binturong) with acute upper respiratory disease was euthanized. Postmortem findings included hepatocellular carcinoma, pancreatic islet cell carcinoma, and renal adenocarcinoma with metastasis to the spleen, pleura, and pericardium. A link between primary hepatic and renal neoplasms has been noted in older humans.

  7. Renal Cell Carcinoma Metastasis from Biopsy Associated Hematoma Disruption during Robotic Partial Nephrectomy

    Directory of Open Access Journals (Sweden)

    Christopher Caputo

    2014-01-01

    Full Text Available We describe a case in which a patient with a past medical history of ovarian cancer received a diagnostic renal biopsy for an incidentally discovered renal mass. During left robotic partial nephrectomy (RPN, a perinephric hematoma was encountered. The hematoma was not present on preoperative imaging and was likely a result of the renal biopsy. The renal cell carcinoma (RCC and the associated hematoma were widely excised with negative surgical margins. On follow-up imaging at five months postoperatively, a recurrent renal mass at the surgical resection bed and several new nodules in the omentum were detected. During completion left robotic total nephrectomy and omental excision, intraoperative frozen sections confirmed metastatic RCC. We believe that a hematoma seeded with RCC formed as a result of the renal biopsy, and subsequent disruption of the hematoma during RPN caused contamination of RCC into the surrounding structures.

  8. Downregulated ECRG4 is associated with poor prognosis in renal cell cancer and is regulated by promoter DNA methylation.

    Science.gov (United States)

    Luo, Liya; Wu, Jianting; Xie, Jun; Xia, Lingling; Qian, Xuemin; Cai, Zhiming; Li, Zesong

    2016-01-01

    Esophageal cancer-related gene 4 (ECRG4) has been proposed as a putative tumor suppressor gene in several tumors. However, the role and regulation of ECRG4 in the pathogenesis of human renal cancer remain largely unknown. Our current study revealed that expression of ECRG4 is downregulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of tumors (p renal cancer patients. Silencing of ECRG4 expression in renal cell lines was associated with its promoter methylation. Moreover, ectopic expression of ECRG4 markedly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicated that ECRG4 is frequently silenced by the methylation of promoter in renal cell cancers. ECRG4 may be a tumor suppressor in renal cancer and serve as a prognostic marker.

  9. Mesenchymal stem cells derived from adipose tissue are not affected by renal disease.

    Science.gov (United States)

    Roemeling-van Rhijn, Marieke; Reinders, Marlies E J; de Klein, Annelies; Douben, Hannie; Korevaar, Sander S; Mensah, Fane K F; Dor, Frank J M F; IJzermans, Jan N M; Betjes, Michiel G H; Baan, Carla C; Weimar, Willem; Hoogduijn, Martin J

    2012-10-01

    Mesenchymal stem cells are a potential therapeutic agent in renal disease and kidney transplantation. Autologous cell use in kidney transplantation is preferred to avoid anti-HLA reactivity; however, the influence of renal disease on mesenchymal stem cells is unknown. To investigate the feasibility of autologous cell therapy in patients with renal disease, we isolated these cells from subcutaneous adipose tissue of healthy controls and patients with renal disease and compared them phenotypically and functionally. The mesenchymal stem cells from both groups showed similar morphology and differentiation capacity, and were both over 90% positive for CD73, CD105, and CD166, and negative for CD31 and CD45. They demonstrated comparable population doubling times, rates of apoptosis, and were both capable of inhibiting allo-antigen- and anti-CD3/CD28-activated peripheral blood mononuclear cell proliferation. In response to immune activation they both increased the expression of pro-inflammatory and anti-inflammatory factors. These mesenchymal stem cells were genetically stable after extensive expansion and, importantly, were not affected by uremic serum. Thus, mesenchymal stem cells of patients with renal disease have similar characteristics and functionality as those from healthy controls. Hence, our results indicate the feasibility of their use in autologous cell therapy in patients with renal disease.

  10. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

    Science.gov (United States)

    Ashouri, Kenan; Mohseni, Sophia; Tourtelot, John; Sharma, Pranav

    2015-01-01

    Von Hippel-Lindau syndrome (VHLS) is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves. This review will discuss the key aspects of the current management of VHLS.

  11. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kenan Ashouri

    2015-09-01

    Full Text Available Von Hippel-Lindau syndrome (VHLS is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves.  This review will discuss the key aspects of the current management of VHLS.

  12. Metastatic renal cell carcinoma from a native kidney of a renal transplant patient diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy

    Directory of Open Access Journals (Sweden)

    Yaseen Alastal

    2015-04-01

    Full Text Available Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy sampling of enlarged lymph nodes is increasingly used to diagnose metastatic tumors, especially of the gastrointestinal tract and the lungs. Herein, we describe the diagnosis of metastatic renal cell carcinoma from a native kidney of a 54 year-old male patient, who had a 5-years history of renal transplant, by EUS-FNA of mediastinal and celiac lymph nodes. Histological and immunohistochemical findings confirmed the origin of metastatic tumor. EUS-FNA with proper cytological evaluation can be useful in the diagnosis of metastatic renal cell carcinoma in renal transplant patients. 

  13. Reduced cilia frequencies in human renal cell carcinomas versus neighboring parenchymal tissue

    Directory of Open Access Journals (Sweden)

    Basten Sander G

    2013-01-01

    Full Text Available Abstract Background Cilia are essential organelles in multiple organ systems, including the kidney where they serve as important regulators of renal homeostasis. Renal nephron cilia emanate from the apical membrane of epithelia, extending into the lumen where they function in flow-sensing and ligand-dependent signaling cascades. Ciliary dysfunction underlies renal cyst formation that is in part caused by deregulation of planar cell polarity and canonical Wnt signaling. Renal cancer pathologies occur sporadically or in heritable syndromes caused by germline mutations in tumor suppressor genes including VHL. Importantly, Von Hippel-Lindau (VHL patients frequently develop complex renal cysts that can be considered a premalignant stage. One of the well-characterized molecular functions of VHL is its requirement for the maintenance of cilia. In this study, tissue from 110 renal cancer patients who underwent nephrectomy was analyzed to determine if lower ciliary frequency is a common hallmark of renal tumorigenesis by comparing cilia frequencies in both tumor and adjacent parenchymal tissue biopsies from the same kidney. Methods We stained sections of human renal material using markers for cilia. Preliminary staining was performed using an immunofluorescent approach and a combination of acetylated-α-tubulin and pericentrin antibodies and DAPI. After validation of an alternative, higher throughput approach using acetylated-α-tubulin immunohistochemistry, we continued to manually quantify cilia in all tissues. Nuclei were separately counted in an automated fashion in order to determine ciliary frequencies. Similar staining and scoring for Ki67 positive cells was performed to exclude that proliferation obscures cilia formation potential. Results Samples from renal cell carcinoma patients deposited in our hospital tissue bank were previously used to compose a tissue microarray containing three cores of both tumor and parenchymal tissue per patient

  14. Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Monika Vyas

    2013-01-01

    Full Text Available Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.

  15. Advanced Renal Failure in Patients with Sickle Cell Anemia: Clinical Course and Prognosis

    Science.gov (United States)

    Cruz, Iluminado A.; Hosten, Adrian O.; Dillard, Martin G.; Castro, Oswaldo L.

    1982-01-01

    Advanced renal failure occurred in nine adult sickle cell disease patients. There were six men and three women with a mean age of 38.6 years. Eight patients had homozygous SS disease, one had sickle cell thalassemia. Three patients had acute renal failure from which they partially recovered. Six developed endstage kidney disease requiring dialysis. Two of these received a kidney transplant, and there was one death in the immediate postoperative period. Angina pectoris, hyperkalemia, and severe anemia complicated chronic dialysis, suggesting that early transplantation should be considered for sickle cell anemia patients with renal failure. PMID:6757451

  16. Gender specific expression of tumor suppressor PKCd versus oncogenic PKCn in renal cell carcinoma

    OpenAIRE

    Brenner, Walburgis; Färber, Gloria; Jan G. Hengstler; Herget, Thomas; Thüroff, Joachim W.; Wiesner, Christoph

    2003-01-01

    Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was ex...

  17. Cadherin-9 is a novel cell surface marker for the heterogeneous pool of renal fibroblasts.

    Directory of Open Access Journals (Sweden)

    Cornelia Thedieck

    Full Text Available BACKGROUND: Interstitial fibroblasts are a minor, but nevertheless very important, component of the kidney. They secrete and remodel extracellular matrix and they produce active compounds such as erythropoietin. However, studying human renal fibroblasts has been hampered by the lack of appropriate surface markers. METHODS AND FINDINGS: The expression of cadherin-9 in various human renal cell lines and tissues was studied on the mRNA level by RT-PCR and on the protein level with the help of newly generated cadherin-9 antibodies. The classical type II cadherin-9, so far only described in the neural system, was identified as a reliable surface marker for renal fibroblasts. Compared to FSP1, a widely-used cytosolic renal fibroblast marker, cadherin-9 showed a more restricted expression pattern in human kidney. Under pathological conditions, cadherin-9 was expressed in the stroma of renal cell carcinoma, but not in the tumor cells themselves, and in renal fibrosis the percentage of cadherin-9-positive cells was clearly elevated 3 to 5 times compared to healthy kidney tissue. Induction of epithelial mesenchymal transition in renal epithelial cells with cyclosporin-A, which causes renal fibrosis as a side effect, induced cadherin-9 expression. Functional studies following siRNA-mediated knockdown of cadherin-9 revealed that it acts in the kidney like a typical classical cadherin. It was found to be associated with catenins and to mediate homophilic but not heterophilic cell interactions. CONCLUSIONS: Cadherin-9 represents a novel and reliable cell surface marker for fibroblasts in healthy and diseased kidneys. Together with the established marker molecules FSP1, CD45 and alpha smooth muscle actin, cadherin-9 can now be used to differentiate the heterogenic pool of renal fibroblasts into resident and activated fibroblasts, immigrated bone marrow derived fibroblast precursors and cells in different stages of epithelial mesenchymal transition.

  18. Decoy cells in the urine cytology of a renal transplant recipient: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Pillai K

    2010-04-01

    Full Text Available Human polyoma virus causes renal dysfunction and graft loss as a result of tubulo-interstial nephritis in renal transplant recipients after reactivation of latent virus in renal epithelium. The infected cells in the urinary sediments are characterized by large homogenous inclusions, which may cause diagnostic error in urine cytology. The epithelial cells with polyoma viral inclusions in urine cytology specimens are termed Decoy cells to caution pathologists not to misdiagnose these cells as cancer cells. We present a case of polyoma viral changes detected the first time in our laboratory in the urine of a 46year old male who underwent renal transplantation six months back and followed by immunotherapy. Urine cytological examination showed decoy cells and subsequently revealed on histopathology. Immunoperoxidase staining for SV-40 LT antigen (LT ag, expression of proliferating cell nuclear antigen (PCNA, p53 and Rb genes were also studied in the tissue sections for further observation. The expression of SV40 LT ag was negative, while PCNA showed strong positivity; p53 and Rb were expressed moderately in the nuclei of cells in the tubules. The report of a case of decoy cells in the urine of a patient with renal transplantation focuses the importance of cytologic analysis of urine as a diagnostic tool for screening renal transplant recipients at risk of polyoma viral infection.

  19. Decoy cells in the urine cytology of a renal transplant recipient: an immunohistochemical study.

    Science.gov (United States)

    Pillai, K Raveendran; Jayasree, K; Pisharody, Ramdas; Abraham, Elizabeth K

    2010-01-01

    Human polyoma virus causes renal dysfunction and graft loss as a result of tubulo-interstial nephritis in renal transplant recipients after reactivation of latent virus in renal epithelium. The infected cells in the urinary sediments are characterized by large homogenous inclusions, which may cause diagnostic error in urine cytology. The epithelial cells with polyoma viral inclusions in urine cytology specimens are termed Decoy cells to caution pathologists not to misdiagnose these cells as cancer cells. We present a case of polyoma viral changes detected the first time in our laboratory in the urine of a 46year old male who underwent renal transplantation six months back and followed by immunotherapy. Urine cytological examination showed decoy cells and subsequently revealed on histopathology. Immunoperoxidase staining for SV-40 LT antigen (LT ag), expression of proliferating cell nuclear antigen (PCNA), p53 and Rb genes were also studied in the tissue sections for further observation. The expression of SV40 LT ag was negative, while PCNA showed strong positivity; p53 and Rb were expressed moderately in the nuclei of cells in the tubules. The report of a case of decoy cells in the urine of a patient with renal transplantation focuses the importance of cytologic analysis of urine as a diagnostic tool for screening renal transplant recipients at risk of polyoma viral infection.

  20. Radiotherapy for renal cell carcinoma: renaissance of an overlooked approach.

    Science.gov (United States)

    Siva, Shankar; Kothari, Gargi; Muacevic, Alexander; Louie, Alexander V; Slotman, Ben J; Teh, Bin S; Lo, Simon S

    2017-06-20

    Conventional radiotherapy previously had a limited role in the definitive treatment of renal cell carcinoma (RCC), owing to the disappointing outcomes of several trials and the perceived radioresistance of this type of cancer. In this context, radiotherapy has been relegated largely to the palliation of symptoms in patients with metastatic disease, with variable rates of response. Following the availability of newer technologies that enable safe delivery of high-dose radiotherapy, stereotactic ablative radiotherapy (SABR) has become increasingly used in patients with RCC. Preclinical evidence demonstrates that RCC cells are sensitive to ablative doses of radiotherapy (≥8-10 Gy). Trials in the setting of intracranial and extracranial oligometastases, as well as primary RCC, have demonstrated excellent tumour control using this approach. Additionally, an awareness of the capacity of high-dose radiation to stimulate antitumour immunity has resulted in novel combinations of SABR with immunotherapies. Here we describe the historical application of conventional radiotherapy, the current biological understanding of the effects of radiation, and the clinical evidence supporting the use of ablative radiotherapy in RCC. We also explore emerging opportunities to combine systemic targeted agents or immunotherapies with radiation. Radiotherapy, although once an overlooked approach, is moving towards the forefront of RCC treatment.

  1. TroVax(®) vaccine therapy for renal cell carcinoma.

    Science.gov (United States)

    Zhang, Rui-Tao; Bines, Steven D; Ruby, Carl; Kaufman, Howard L

    2012-01-01

    Renal cell carcinoma (RCC) is the most common primary malignancy affecting the kidney. In the past decade, several well-designed clinical trials have shifted the treatment paradigm for RCC to favor targeted therapies as first-line agents. Recognition of the immunogenic nature of RCC has also resulted in the development of immunotherapy approaches with high-dose IL-2 treatment being the best established and associated with durable disease control. The lack of defined antigens in RCC has hindered more specific vaccine development. TroVax(®) is a novel vaccine based on a modified vaccinia virus Ankara vector engineered to express the 5T4 tumor-associated antigen, found on over 95% of clear cell and papillary RCC tumors. The safety and efficacy of TroVax has been evaluated in several Phase I/II clinical trials and in a multicenter Phase III trial. This article will discuss the clinical background of RCC, the rationale for TroVax development, results of several TroVax clinical trials and future directions for optimizing TroVax therapy in patients with RCC and other cancers.

  2. Renal Medullary Cancer in a Patient with Sickle Cell Trait

    Directory of Open Access Journals (Sweden)

    Narendrakumar Alappan

    2013-01-01

    Full Text Available Renal medullary cancer is a rare malignancy almost exclusively seen in young patients of African ethnicity. These patients often present with the cardinal symptoms of hematuria, flank pain, and an abdominal mass, and this malignancy has been associated with patients carrying sickle cell trait. It is estimated that 300 million people worldwide carry sickle cell trait, and the presence of hematuria in these patients should be treated as a harbinger of a possible malignancy. Notably, this tumor mostly develops on the right side of the body. Patients often present with it at an advanced stage and the prognosis is poor. Therefore, a high index of suspicion in a patient of African descent presenting with a right sided abdominal mass and hematuria may assist in an early diagnosis. Current chemotherapy options are very limited, and early detection may provide a chance for surgical resection. It may also provide a bigger time frame for the initiation of novel chemotherapy regimens in patients who fail current chemotherapy regimens.

  3. Renal medullary cancer in a patient with sickle cell trait.

    Science.gov (United States)

    Alappan, Narendrakumar; Marak, Creticus P; Chopra, Amit; Joy, Parijat S; Dorokhova, Olena; Guddati, Achuta K

    2013-01-01

    Renal medullary cancer is a rare malignancy almost exclusively seen in young patients of African ethnicity. These patients often present with the cardinal symptoms of hematuria, flank pain, and an abdominal mass, and this malignancy has been associated with patients carrying sickle cell trait. It is estimated that 300 million people worldwide carry sickle cell trait, and the presence of hematuria in these patients should be treated as a harbinger of a possible malignancy. Notably, this tumor mostly develops on the right side of the body. Patients often present with it at an advanced stage and the prognosis is poor. Therefore, a high index of suspicion in a patient of African descent presenting with a right sided abdominal mass and hematuria may assist in an early diagnosis. Current chemotherapy options are very limited, and early detection may provide a chance for surgical resection. It may also provide a bigger time frame for the initiation of novel chemotherapy regimens in patients who fail current chemotherapy regimens.

  4. Genetic characteristics of the non-clear cell renal cancer

    Directory of Open Access Journals (Sweden)

    D. S. Mikhaylenko

    2016-01-01

    Full Text Available Renal cancer (RC is one of the most frequent diseases in oncological urology; the most common form of RC is the clear cell carcinoma. However, percentage of less-studied non-clear cell RC (nccRC reaches up to 25 % of cases suggesting further studying, improvement of diagnosis and treatment of these tumors. The key events of carcinogenesis are genetic alterations including chromosomal aberrations and point mutations in proto-oncogenes and tumor suppressor genes. This review describes cytogenetic aberrations in the context of nccRC diversity according to the current ISUP classification. Translocation variants of nccRC (MiT-RC were characterized separately as particular cases of the chromosome rearrangements involving MiT gene family (TFE3, TFEB, MITF. In addition, the main nccRC hereditary forms caused by germinal mutations in the genes FLCN, FH, and MET, as well as recent studies of sporadic tumors with using the next generation sequencing techniques were reviewed. These experiments were designed to search for somatic mutations throughout the tumor genome or exom and revealed the different mutational profiles of I/II papillary RC subtypes, chromophobe carcinoma versus oncocytoma. The review may be informative for oncologists, urologists, geneticists and specialists in related sciences. 

  5. Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Arash Akhavein

    2014-05-01

    Full Text Available Xp11 translocation renal cell carcinoma (TRCC is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor–targeted therapy in case of recurrence.

  6. CD 9 and vimentin distinguish clear cell from chromophobe renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ljunberg Börje

    2009-11-01

    Full Text Available Abstract Background Clear cell renal cell carcinoma (ccRCC and chromophobe renal cell carcinoma (chRCC can usually be distinguished by histologic characteristics. Occasionally, diagnosis proves challenging and diagnostic difficulty will likely increase as needle biopsies of renal lesions become more common. Methods To identify markers that aid in differentiating ccRCC from chRCC, we used gene expression profiles to identify candidate markers that correlate with histology. 39 antisera and antibodies, including 35 for transcripts identified from gene expression profiling, were evaluated. Promising markers were tested on a tissue microarray (TMA containing 428 renal neoplasms. Strength of staining of each core on the TMA was formally scored and the distribution of staining across different types of renal neoplasms was analyzed. Results Based on results from initial immunohistochemical staining of multitissue titer arrays, 23 of the antisera and antibodies were selected for staining of the TMA. For 7 of these markers, strength of staining of each core on the TMA was formally scored. Vimentin (positive in ccRCC and CD9 (positive in chRCC best distinguished ccRCC from chRCC. The combination of vimentin negativity and CD9 positivity was found to distinguish chRCC from ccRCC with a sensitivity of 100.0% and a specificity of 95.2%. Conclusion Based on gene expression analysis, we identify CD9 and vimentin as candidate markers for distinguishing between ccRCC and chRCC. In difficult cases and particularly when the amount of diagnostic tissue is limited, vimentin and CD9 staining could serve as a useful adjunct in the differential diagnosis of ccRCC and chRCC.

  7. Neovascularity as a prognostic marker in renal cell carcinoma.

    Science.gov (United States)

    Bauman, Tyler M; Huang, Wei; Lee, Moon Hee; Abel, E Jason

    2016-11-01

    Endothelial markers platelet and endothelial cell adhesion molecule (PECAM-1), cluster of differentiation (CD31) and endoglin (CD105) may be used to identify endothelium and activated endothelium, respectively, with the CD105/CD31 ratio used to measure neovascularity. This study investigated the hypothesis that neovascularity in renal cell carcinoma (RCC) is associated with more aggressive RCC tumors and can be used to predict oncological outcomes. Multiplexed immunohistochemistry using antibodies to detect endoglin and PECAM-1 was performed on tissue microarray of benign kidney samples and RCC tumors including clear cell, papillary, chromophobe, and collecting duct and unclassified tumors (combined for statistics), and multispectral imaging was used for analysis. The CD105/CD31 ratio was compared with clinical and pathologic features of RCC as well as clinical outcomes after surgery using Cox proportional hazards regression and Kaplan-Meier analysis. A total of 502 tumor samples and 122 normal kidney samples from 251 RCC patients were analyzed. The average CD105/CD31 expression ratio, an indicator of neovascularization, was increased in higher pathologic stage tumors (P< .0001). Among RCC morphotypes, the ratio was lower in papillary RCC morphotype tumors (P= .001) and higher in collecting duct/unclassified tumors (P= .0001) compared with clear cell RCC. Among nuclear grades, grade 4 RCC displayed a significantly elevated CD105/CD31 ratio (P< .0001). In multivariable analysis, increased neovascularity was associated with decreased overall survival (hazard ratio, 1.54 [95% confidence interval, 1.06-2.23]; P= .02). In patients receiving anti-vascular endothelial growth factor therapy (VEGF, n = 13) for metastatic RCC, a low CD105/CD31 ratio was associated with increased survival (P= .02). We conclude that higher neovascularity is associated with worse outcomes after surgery for RCC. The ratio of CD105/CD31 expression is a potential indicator of response to anti

  8. Reference Genes for Gene Expression Analysis by Real-time Reverse Transcription Polymerase Chain Reaction of Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Pedersen, Shona; Kristensen, Søren Risom

    2011-01-01

    Differentiation between malignant renal cell carcinoma and benign oncocytoma is of great importance to choose the optimal treatment. Accurate preoperative diagnosis of renal tumor is therefore crucial; however, existing imaging techniques and histologic examinations are incapable of providing...

  9. The proximal tubular cell, a key player in renal damage

    NARCIS (Netherlands)

    Timmeren, Mirjan Miranda van

    2008-01-01

    A decline in renal function is associated with the degree of proteinuria and with histological findings of glomerulosclerosis and interstitial fibrosis. Proteinuria is not only a marker of renal damage, but ultrafiltered proteins can be toxic to the kidney, thereby contributing to tubulo-interstitia

  10. Bone marrow-derived cells in renal repair

    NARCIS (Netherlands)

    Broekema, Martine

    2007-01-01

    The kidney can recover after acute renal injury due to its highly effective endogenous regenerative capacity. However, under certain conditions the balance between injury and repair can get disturbed. This can ultimately lead to chronic renal failure, which is an increasing problem in the clinical s

  11. Trisacryl Gelatin Microembolism and Metastases in the Lung after Renal Artery Embolization and Nephrectomy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Andres Borja Alvarez

    2015-01-01

    Full Text Available This is the first report, to our knowledge, of widespread, histologically confirmed trisacryl gelatin pulmonary microembolism after renal artery embolization (RAE. In addition, this is the first report of lung involvement by both metastatic renal cell carcinoma (RCC and an embolic agent used for RAE. The patient was a 63-year-old woman who recently presented with both dyspnea on exertion and productive cough. Her past medical history included clear cell RCC, which was treated with preoperative trisacryl gelatin microsphere RAE and right nephrectomy 9 years earlier. Computed tomography of the chest showed multiple lung nodules, a mass-like density in the left lower lobe, and mediastinal and hilar lymphadenopathy. Wedge resections of the lung showed multiple foci of metastatic RCC and extensive involvement of the muscular pulmonary arteries by trisacryl gelatin microspheres.

  12. In vitro selection of DNA aptamers against renal cell carcinoma using living cell-SELEX.

    Science.gov (United States)

    Wang, Jine; Zhang, Yajie; Chen, Yang; Hong, Shanni; Sun, Yan; Sun, Na; Pei, Renjun

    2017-12-01

    Renal cell carcinoma (RCC) is the most common form of kidney cancer with poor prognosis. Early diagnosis of RCC would significantly improve patient prognosis and quality of life. In this work, we developed new aptamer probes for RCC by using cell-SELEX (systematic evolution of ligands by exponential enrichment) only after 12 rounds of selection, in which a clear cell renal cell carcinoma (ccRCC) cell line 786-O was used as target cell, and embryonic kidney cell line 293T as negative control cell. The selected aptamers were subjected to flow cytometry and laser confocal fluorescence microscopy to evaluate their binding affinity and selectivity. The dissociation constant Kd values of four selected aptamers are all in the nanomolar range. Aptamer W786-1 with the best binding affinity and a Kd value of 9.4 ± 2.0nM was further optimized and its truncated sequence W786-1S showed considerable affinity to 786-O cells. The proteinase and temperature treatment experiment indicated that W786-1 could recognize the target 786-O cells through surface proteins, and remain good binding affinity and excellent selectivity under physiological conditions. Therefore, on the basis of its excellent targeting properties and functional versatility, W786-1 holds great potential to be used as a molecular probe for identifying and targeting RCC. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. LMP2, a novel immunohistochemical marker to distinguish renal oncocytoma from the eosinophilic variant of chromophobe renal cell carcinoma.

    Science.gov (United States)

    Zheng, Gang; Chaux, Alcides; Sharma, Rajni; Netto, George; Caturegli, Patrizio

    2013-02-01

    LMP2 is a subunit of the immunoproteasome that is overexpressed in oncocytic lesions of the thyroid gland. This study was designed to assess the expression profile and diagnostic utility of LMP2 in two renal oncocytic tumors that share similar morphologic features but have different clinical outcomes: renal oncocytoma (RO) and the eosinophilic variant of chromophobe renal cell carcinoma (CHRCC-EO). A total of 56 RO, 38 classic CHRCC, and 7 CHRCC-EO cases, as well 84 normal kidney controls, were selected from the Johns Hopkins surgical pathology archive and stained for LMP2 using a standard immunohistochemical protocol. Sections were scored for cellular location (nuclear versus cytosolic), intensity (from 0 to 3), and percent of area involved (from 0 to 100%), and an H score was calculated multiplying the intensity by the extent of the staining signal. The cytoplasmic expression of LMP2 was similar among the renal lesions, being present in 44 of 56 (79%) ROs, 27 of 38 (71%) CHRCCs, and 7 of 7 (100%) CHRCC-EO cases. The nuclear expression of LMP2, however, was more informative. All CHRCC-EO cases (7 of 7, 100%) strongly showed nuclear LMP2 staining, as opposed to only 2 of 56 (4%, P<0.0001) ROs and 9 of 38 (24%, P=0.0001) classic CHRCCs. These results suggest that the nuclear LMP2 expression can be used in clinical scenarios where histological distinction between RO and CHRCC-EO remains challenging.

  14. Testicular metastasis of renal cell carcinoma mimicking seminoma; Metastasis testicular de adenocarcinoma de celulas renales simulando un seminoma

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, P.; Marco, S. F.; Gil, S.; Cervera, J. [Hospital General de Castellon. (Spain)

    1999-07-01

    We report a case of renal cell carcinoma presenting with secondary signs resulting from this lesion, and review the pertinent literature. The interesting aspect of this case is its uncommon presentation as a testicular metastasis that mimicked a seminomatous lesion associated with a lytic lesion in ipsilateral ilium. These findings lend additional support to the need to perform thoracoabdominal computed tomography for staging of testicular neoplasms discovered by ultrasound prior to surgery. (Author) 21 refs.

  15. Clear cell renal cell carcinoma with hemangioblastoma-like features: A recently described pattern with unusual immunohistochemical profile

    Directory of Open Access Journals (Sweden)

    Sankalp Sancheti

    2015-01-01

    Full Text Available The diagnosis of clear cell renal cell carcinoma may sometimes pose challenges because of the presence of uncharacteristic morphology, varied immunophenotypic patterns and due to lack of molecular or genetic determinants. More often, the morphological variations can be easily overlooked in routine practice and a more common diagnosis is usually put forward. Solid, acinar and alveolar are the common patterns described in the literature. We report a recently described pattern of clear cell renal cell carcinoma which has hemangioblastoma-like morphology and an unusual immunoprofile. In our case, the tumor showed a diffuse hemangioblastoma-like pattern and diffuse positivity for Alpha-inhibin on immunohistochemistry. A thorough literature search, extensive sampling and an expanded immunohistochemistry panel revealed a clear cell renal cell carcinoma component. Presence of renal vein thrombosis and focal necrosis were other helpful features in discerning the malignant nature of tumor.

  16. Differentiations of transplanted mouse spermatogonial stem cells in the adult mouse renal parenchyma in vivo

    Institute of Scientific and Technical Information of China (English)

    Da-peng WU; Da-lin HE; Xiang LI; Zhao-hui LIU

    2008-01-01

    Aim:Spermatogonial stem cells can initiate the process of cellular differentia-tion to generate mature spermatozoa, but whether it possess the characteristic of pluripotency and plasticity, similar to embryonic stem cells, has not been elucidated. This study was designed to evaluate the differentiation potential of spermatogonial stem cells into renal cells in vivo. Methods: Neonatal mouse spermatogonial stem cells were transplanted into mature male mice lacking en-dogenous spermatogenesis. The restoration of fertility in recipient males was observed. Spermatogonial stem cells were then injected into renal parenchyma of mature female mice to make a new extracellular environment for differentia-tion. Fluorescence in situ hybridization technology (FISH) was used to detect the expression of chromosome Y in recipient renal tissues. To determine the type of cells differentiated from spermatogonial stem cells, the expression of ricinus communis agglutinin, vimentin, CD45, and F4/80 proteins were examined in the renal tissues by immunohistochemistry. Results: The proliferation of seminiferous epithelial cells was distinctly observed in seminiferous tubules of transplanted testes, whereas no regeneration of spermatogenesis was observed in non-transplanted control testes. In transplanted female renal tissues, FISH showed a much stronger immuno-fluorescence signal of chromosome Y in the nucleolus of epithelial cells of the renal tubule and podocytes of the glomerulus. Conclusion: The spermatogonial stem cells were successfully purified from mouse testicles. This finding demonstrated that spermatogonial stem cells could not only restore damaged spermatogenesis, but were also capable of differentiat-ing into mature renal parenchyma cells in vivo.

  17. Auxin induces cell proliferation in an experimental model of mammalian renal tubular epithelial cells.

    Science.gov (United States)

    Cernaro, Valeria; Medici, Maria Antonietta; Leonello, Giuseppa; Buemi, Antoine; Kohnke, Franz Heinrich; Villari, Antonino; Santoro, Domenico; Buemi, Michele

    2015-06-01

    Indole-3-acetic acid is the main auxin produced by plants and plays a key role in the plant growth and development. This hormone is also present in humans where it is considered as a uremic toxin deriving from tryptophan metabolism. However, beyond this peculiar aspect, the involvement of auxin in human pathophysiology has not been further investigated. Since it is a growth hormone, we evaluated its proliferative properties in an in vitro model of mammalian renal tubular epithelial cells. We employed an experimental model of renal tubular epithelial cells belonging to the LLC-PK1 cell line that is derived from the kidney of healthy male pig. Growth effects of auxin against LLC-PK1 cell lines were determined by a rapid colorimetric assay. Increasing concentrations of auxin (to give a final concentration from 1 to 1000 ng/mL) were added and microplates were incubated for 72 h. Each auxin concentration was assayed in four wells and repeated four times. Cell proliferation significantly increased, compared to control cells, 72 h after addition of auxin to cultured LLC-PK1 cells. Statistically significant values were observed when 100 ng/mL (p auxin influences cell growth not only in plants, where its role is well documented, but also in mammalian cell lines. This observation opens new scenarios in the field of tissue regeneration and may stimulate a novel line of research aiming at investigating whether this hormone really influences human physiology and pathophysiology and in particular, kidney regeneration.

  18. Spatially resolved shear distribution in microfluidic chip for studying force transduction mechanisms in cells.

    Science.gov (United States)

    Wang, Jianbin; Heo, Jinseok; Hua, Susan Z

    2010-01-21

    Fluid shear stress has profound effects on cell physiology. Here we present a versatile microfluidic method capable of generating variable magnitudes, gradients, and different modes of shear flow, to study sensory and force transduction mechanisms in cells. The chip allows cell culture under spatially resolved shear flow conditions as well as study of cell response to shear flow in real-time. Using this chip, we studied the effects of chronic shear stress on cellular functions of Madin-Darby Canine Kidney (MDCK), renal epithelial cells. We show that shear stress causes reorganization of actin cytoskeleton, which suppresses flow-induced Ca(2+) response.

  19. Epidemiologic characteristics of renal cell carcinoma in Brazil

    Directory of Open Access Journals (Sweden)

    Aguinaldo C. Nardi

    2010-04-01

    Full Text Available PURPOSE: In Brazil, National data regarding the epidemiology of renal cell carcinoma (RCC are scarce. The aim of this study was to describe the demographic, clinical, and pathologic characteristics of RCC diagnosed and treated by members of the SBU - Brazilian Society of Urology. MATERIALS AND METHODS: For this cross-sectional study, data were collected through an on line questionnaire available to the members of the Brazilian Society of Urology (SBU. Between May 2007 and May 2008, voluntary participant urologists collected data on demographic, clinical and pathological characteristics from patients diagnosed with RCC in their practice. RESULTS: Fifty SBU affiliated institutions contributed with patient information to the study. Of the 508 patients, 58.9% were male, 78.9% were white, and the mean age was 59.8 years. Smoking history, high blood pressure and a body mass index above 30 kg/m2 were present in 14.8%, 46.1% and 17.9% of the patients, respectively. Abdominal ultrasound and computed tomography were the main diagnostic methods. The majority of the cases were localized tumors and metastasis were presented in 9.5% of the patients; 98.4% underwent nephrectomy. Clear cell carcinoma was the most common histological type. In comparison with private institutions, stage IV disease was less frequent among patients treated at public health services (P = 0.033. CONCLUSIONS: RCC in Brazil is more common in white men in their sixth decade of life. Ultrasound is the main diagnostic tool for the diagnosis of clear cell carcinoma and we found that localized disease was predominant. A national registry of RCC is feasible and may provide valuable information.

  20. Rate of renal cell carcinoma subtypes in different races

    Directory of Open Access Journals (Sweden)

    Alexander Sankin

    2011-02-01

    Full Text Available PURPOSE: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC between black and non-black patients in an equal-access health care system. MATERIALS AND METHODS: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. RESULTS: 204 kidney tumors were identified (Table-1. Of these, 117 (57.4% were in black patients and 87 (42.6% were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%, papillary RCC in 65 cases (31.9%, chromophobe RCC in 13 cases (6.4%, collecting duct/medullary RCC in 2 cases (1.0%, RCC with multiple histological subtypes in 8 cases (3.9%, malignant tumors of other origin in 6 cases (2.9%, and benign histology in 13 cases (6.4%. Among black patients, papillary RCC was seen in 56 cases (47.9%, compared to 9 cases (10.3% among non-black patients (p < 0.001 (Table-2. Clear cell RCC was present in 38 (32.5% of black patients and in 59 (67.8% of non-blacks (p < 0.001. CONCLUSIONS: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

  1. Synchronous sigmoid and caecal cancers together with a primary renal cell carcinoma.

    LENUS (Irish Health Repository)

    Bhargava, A

    2012-06-01

    Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms.

  2. A unique presentation of a renal clear cell carcinoma with atypical metastases

    Directory of Open Access Journals (Sweden)

    F. Staderini

    2015-01-01

    Conclusion: Recent series highlight surgery as a key-point in the management of advanced renal clear cell carcinoma. Our case demonstrates the validity of a surgical strategy supported by a multidisciplinary approach.

  3. CYTOGENETIC ANALYSIS OF EPITHELIAL RENAL-CELL TUMORS - RELATIONSHIP WITH A NEW HISTOPATHOLOGICAL CLASSIFICATION

    NARCIS (Netherlands)

    VANDENBERG, E; VANDERHOUT, AH; OOSTERHUIS, JW; STORKEL, S; DIJKHUIZEN, T; ZWEERS, HMM; MENSINK, HJA; BUYS, CHCM; DEJONG, B; Dam, A.

    1993-01-01

    Renal-cell carcinomas (RCC) are clinically, histologically and cytogenetically very heterogeneous. The present histological WHO classification shows no clear correlation between histologic subtypes and specific chromosomal abnormalities. In 1986, a new classification was proposed by Thoenes and

  4. Atypical presentation of primary renal squamous cell cancer: a case report

    Directory of Open Access Journals (Sweden)

    Mrinal Pahwa

    2014-02-01

    Full Text Available Renal squamous cell cancer is one of the rare primary urothelial tumors with only a handful of cases reported in literature. Because of high grade, advanced and late presentation, they herald a grave prognosis. They are frequently associated with calculus disease, smoking, phenacetin consumption and foci of squamous metaplasia due to chronic irritation. Nephroureterectomy is the treatment of choice for such tumors. We hereby present a case of 59 year old female who presented with squamous cell cancer of renal pelvis. The case presented here is different from what has already been reported in literature, as the patient had no antecedent risk factors for renal squamous cell carcinoma.-------------------------------------------------Cite this article as: Pahwa M, Pahwa AR, Girotra M, Chawla A. Atypical presentation of primary renal squamous cell cancer: a case report. Int J Cancer Ther Oncol 2014; 2(1:02015.DOI: http://dx.doi.org/10.14319/ijcto.0201.5

  5. Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

    Science.gov (United States)

    Johnston, Kimberly A; Westover, Angela J; Rojas-Pena, Alvaro; Buffington, Deborah A; Pino, Christopher J; Smith, Peter L; Humes, H David

    2016-11-18

    Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 10(8) renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Perioperative outcomes of laparoscopic radical nephrectomy for renal cell carcinoma in patients with dialysis-dependent end-stage renal disease.

    Science.gov (United States)

    Yamashita, Kaori; Ito, Fumio; Nakazawa, Hayakazu

    2012-06-01

    The aims of this study were: (i) to analyze the perioperative outcomes of laparoscopic radical nephrectomy for renal cell carcinoma in patients with dialysis-dependent end-stage renal disease and (ii) to reveal perioperative management problems that are unique to these patients. Between June 2004 and June 2011, laparoscopic radical nephrectomy was performed in 39 patients who had renal cell carcinoma and dialysis-dependent end-stage renal disease. The operative outcomes of these patients were compared with the operative outcomes of 104 non-end-stage renal disease patients with sporadic renal cell carcinoma who underwent laparoscopic radical nephrectomy during the same period. Laparoscopic surgery was completed in thirty-eight end-stage renal disease patients. One patient was converted to open surgery because of an intraoperative injury to the inferior vena cava. This patient was excluded from the analysis. The mean operative time was 240 min; blood loss, 157 mL; and postoperative hospital stay, 9.6 days. Postoperative complications were observed in six patients, as follows: retroperitoneal hematoma and abscess in one patient, thrombosis of the arteriovenous fistula in three patients, pneumonia in one patient, and gastrointestinal bleeding in one patient. Eleven patients required blood transfusions. There was no significant difference between the end-stage renal disease patients and the non-end-stage renal disease patients in the mean operative time or the amount of blood loss. In conclusion, laparoscopic radical nephrectomy is feasible for dialysis-dependent end-stage renal disease patients, as well as for non-end-stage renal disease patients; however, end-stage renal disease patients may have a higher probability of experiencing non-life-threatening complications.

  7. Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio [Jichi Medical School, Division of Environmental Medicine, Center for Community Medicine, Tochigi (Japan); Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST), Saitama (Japan)

    2006-10-15

    The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production. (orig.)

  8. Cardiac metastasis from renal cell carcinoma successfully treated with pazopanib: impact of TKIs' antiangiogenic activity.

    Science.gov (United States)

    Schinzari, Giovanni; Monterisi, Santa; Signorelli, Diego; Cona, Silvia; Cassano, Alessandra; Danza, Francesco; Barone, Carlo

    2014-01-01

    Cardiac metastasis from renal cell carcinoma, especially without neoplastic thrombosis of the vena cava, is extremely rare. The prognosis of patients with metastatic renal cell carcinoma has been radically influenced by the introduction of tyrosine kinase inhibitors, but very few reports in the literature have described their activity in heart metastasis. We report the case of a woman with a left ventricle metastasis from kidney cancer without renal vein involvement, who was treated with pazopanib. The patient achieved a prolonged partial response, with clear signs of metastasis devascularization and a favorable toxicity profile.

  9. Analysis of renal cancer cell lines from two major resources enables genomics-guided cell line selection

    Science.gov (United States)

    Sinha, Rileen; Winer, Andrew G.; Chevinsky, Michael; Jakubowski, Christopher; Chen, Ying-Bei; Dong, Yiyu; Tickoo, Satish K.; Reuter, Victor E.; Russo, Paul; Coleman, Jonathan A.; Sander, Chris; Hsieh, James J.; Hakimi, A. Ari

    2017-05-01

    The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines.

  10. Hyponatremia as a prognostic and predictive factor in metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Jeppesen, A N; Jensen, H K; Donskov, Frede;

    2010-01-01

    Low serum sodium has recently been associated with poor survival in localised renal cell carcinoma (RCC). We now show the prognostic effect of serum sodium in patients with metastatic RCC (mRCC).......Low serum sodium has recently been associated with poor survival in localised renal cell carcinoma (RCC). We now show the prognostic effect of serum sodium in patients with metastatic RCC (mRCC)....

  11. The importance of histology and cytogenetics in decision making for renal cell carcinoma.

    Science.gov (United States)

    Garcia, Julia G; Picken, Maria M; Flanigan, Robert C

    2008-04-01

    The role of histology and cytogenetics in the diagnosis of renal cell carcinoma continues to evolve. The symbiotic relationship between histology and cytogenetics helps assure the most accurate diagnosis. Prognostic factors are known and continue to be undiscovered. Patient counseling certainly benefits from this information. Further knowledge and differentiation of renal cell carcinoma disease pathways has allowed for the development of targeted therapies. The benefit of these therapies hinges on the critical diagnosis attained via the role of histology and cytogenetics.

  12. Metastatic Renal Cell Carcinoma to the Parotid Gland in the Setting of Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Robert Deeb

    2012-01-01

    Full Text Available Renal cell carcinoma (RCC is infamous for its unpredictable behavior and metastatic potential. We report a case of a patient with a complex history of multifocal renal cell carcinoma and chronic lymphocytic leukemia (CLL, who subsequently developed a parotid mass. Total parotidectomy revealed this mass to be an additional site of metastasis which had developed 19 years after his initial diagnosis of RCC.

  13. CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells.

    Science.gov (United States)

    Liu, Xuejiao; Chong, Yulong; Liu, Huize; Han, Yan; Niu, Mingshan

    2016-03-01

    Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor eff ects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory eff ect of S109 on CRM1 is reversible. Our data demonstrated that S109 signifi cantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the eff ects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.

  14. DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

    Science.gov (United States)

    Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

    2014-07-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death.

  15. Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Rachna Raman

    2015-01-01

    Full Text Available Localized renal cell carcinoma (RCC is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

  16. Update on contemporary management of clinically localized renal cell carcinoma.

    Science.gov (United States)

    Jorns, J J; Thiel, D D; Castle, E P

    2012-12-01

    Renal cell carcinoma (RCC) continues to increase in incidence with the largest increase manifesting in small, organ-confined tumors. This review outlines the epidemiology and current data pertaining to the management of clinically-localized RCC. In this manuscript, the current data outlining the benefit of nephron sparing to the overall survival of the patient is described. The data pertaining to minimally invasive nephron sparing is also explained in detail. From laparoscopic and robotic partial nephrectomy to watchful waiting and percutaneous ablation, the urologist is continually assaulted with new data for the management of clinically-localized RCC. The data can be confusing, and much of it is conflicting. The addition of new scoring systems or nomograms may aid in predicting which therapy would be most beneficial in certain patient groups. New scoring systems may also predict the difficulty of surgical resection and predict surgical complications. The limitations of the data pertaining to the management of clinically-localized RCC are also outlined.

  17. Usefulness of resistive index on spectral Doppler ultrasonography in the detection of renal cell carcinoma in patients with end-stage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Youn; Woo, Sung Min; Cho, Jeong Yeon; Kim, Seung Hyup [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Hwang, Sung Il; Lee, Hak Jong [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Moon, Min Hoan; Sung, Chang Kyu [Dept. of adiology, Seoul National University Boramae Hospital, Seoul (Korea, Republic of)

    2014-04-15

    The aim of this study was to explore the usefulness of the resistive index (RI) on spectral Doppler ultrasonography (US) in the detection of renal cell carcinoma (RCC) in patients with end-stage renal disease (ESRD). Seventeen ESRD patients with kidneys in which renal masses were suspected in routine US were subjected. They underwent computed tomography scans and additional Doppler US for the characterization of the detected lesions. All underwent radical nephrectomy with the suspicion of RCC. Fourteen patients finally were included. RI measurements were conducted in the region of the suspected renal mass and the background renal parenchyma. The intra class correlation coefficient was used to assess the reproducibility of the RI measurement. A paired t-test was used to compare the RI values between the renal mass and the background renal parenchyma (P<0.05). The RI values measured at the RCCs were significantly lower than those measured at the background renal parenchyma (0.41-0.65 vs. 0.75-0.89; P<0.001). The intrareader reproducibility proved to be excellent and good for the renal masses and the parenchyma, respectively (P<0.001). RI on spectral Doppler US is useful in detecting RCC in patients with ESRD. The RI values measured at the RCCs were significantly lower than those measured at the background renal parenchyma.

  18. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Science.gov (United States)

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

    The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of

  19. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  20. Continuous production of erythropoietin by an established human renal carcinoma cell line: development of the cell line

    Energy Technology Data Exchange (ETDEWEB)

    Sherwood, J.B.; Shouval, D.

    1986-01-01

    Establishment of a stable, transformed human renal carcinoma cell line that produces erythropoietin in vitro and has maintained this function continuously since 1981 and for > 150 passages in monolayer culture was accomplished by transplantation of human renal clear cell carcinoma tissue from a patient with erythrocytosis into an immunosuppressed athymic mouse. In addition to its immunocrossreactivity with native human urinary erythropoietin, the tumor erythropoietin demonstrates biological activity in the in vitro mouse erythroid colony-forming unit assay and in tumor-bearing nude mice. The cloned renal carcinoma cell line has an abnormal human karyotype and has ultrastructural features characteristic of human renal clear cell carcinoma. This cell line provides a reproducible model system for the production of an erythropoietin-like material and for the study of its synthesis and secretion.

  1. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    Science.gov (United States)

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study.

  2. Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence.

    Science.gov (United States)

    Ofo, Enyinnaya; Mandavia, Rishi; Jeannon, Jean-Pierre; Odell, Edward; Simo, Ricard

    2014-01-01

    Metastases to the parathyroid gland are very uncommon. Although renal cell carcinoma metastasis to the head and neck region is well recognised, with a predilection for unpredictable metastasis to unusual sites such as the thyroid gland, nose, paranasal sinuses, and cranial bones, there are no reports of parathyroid gland involvement. We describe an unusual case of renal cell carcinoma metastasis to a parathyroid gland in a 69-year-old male who had been treated 8 years previously for a pT3b N0 M1 clear cell carcinoma of the right kidney with a right nephrectomy, and interferon immunotherapy for 18 months. The patient had originally presented to the plastic surgeons with a rapidly enlarging 3cm superficial lesion on the ventral aspect of the left forearm, which was excised with histology revealing metastatic renal (clear) cell carcinoma. Renal cell carcinoma has a reputation for unpredictable patterns of metastasis, and our case highlights this, with the first description in the literature of parathyroid gland metastasis. Despite the poor prognosis associated with metastatic renal cell carcinoma, our patient is still alive 10 years following original presentation, despite having metastasis to two different extra-renal sites and a shortened course of initial adjuvant systemic therapy. In parathyroid gland metastasis, metastectomy can offer excellent local long term local control. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. An obscure cause of gastrointestinal bleeding: Renal cell carcinoma metastasis to the small bowel

    Directory of Open Access Journals (Sweden)

    Robyn L. Gorski

    2015-01-01

    Full Text Available Renal cell carcinoma metastasis to the small intestine is a rare condition. It usually results in gastrointestinal bleeding and it could happen many years after the diagnosis with renal cell cancer. Treatment includes surgery as well as targeted agents such as tyrosine kinases. We report here the case of an 82-year-old man with a past medical history of high-grade renal cell carcinoma and right nephrectomy 6 years earlier, who presented with recurrent episodes of syncope and black stools. He underwent esophagogastroduodenoscopy (EGD and colonoscopy without evident source of bleeding. Video capsule endoscopy (VCE showed three bleeding lesions in the jejunum and ileum. Push enteroscopy revealed a proximal jejunum bleeding mass that was suspicious for malignancy. Histopathology demonstrated poorly differentiated carcinoma. Given the patient’s history of high-grade renal cell carcinoma, and similarity of histologic changes to the old renal cell cancer specimen, metastatic renal cell carcinoma was felt to be the responsible etiology.

  4. Interventions to improve chronic cyclosporine A nephrotoxicity through inhibiting renal cell apoptosis: a systematic review

    Institute of Scientific and Technical Information of China (English)

    XIAO Zheng; LI Cheng-wen; SHAN Juan; LUO Lei; FENG Li; LU Jun; LI Sheng-fu

    2013-01-01

    Objective To reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies,we analyzed all relevant studies about interventions in renal cell apoptosis.Data sources We collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010),Embase (1980 to July 2010) and ISI (1986 to July 2010),evaluated their quality,extracted data following PICOS principles and synthesized the data.Study selection We included all relevant studies about interventions in CsA-induced renal cell apoptosis no limitation of research design and language) and excluded the duplicated articles,meeting abstracts and reviews without specific data.Results There were three kinds of intervention,include anti-oxidant (sulfated polysaccharides,tea polyphenols,apigenin,curcumin,spirulina,etc),biologics (recombinant human erythropoietin (rhEPO),a murine pan-specific transforming growth factor (TGF)-beta-neutralizing monoclonal antibody1D11,cartilage oligomeric matrix protein (COMP)-angiopoietin-1 and hepatocyte growth factor (HGF) gene),and other drugs (spironolactone,rosiglitazone,pirfenidone and colchicine).These interventions significantly improved the CCN,renal cell apoptosis and renal dysfunction through intervening in four apoptotic pathways in animals or protected renal cells from apoptosis induced by CsA and increased cell survival through respectively four pathways in vitro.Conclusions There are three group interventions for CCN.Especially anti-oxidant drugs can significantly improve CCN,renal cell apoptosis and renal dysfunction.Many drugs can improve CCN through intervening in Fas/Fas ligand or mitochondrial pathway with sufficient evidences.Angiotensin Ⅱ,nitric oxide (NO) and endoplasmic reticulum (ER) pathways will be new targets for CCN.

  5. Mecanismos del daño celular en la insuficiencia renal aguda Mechanisms of cell damage in acute renal failure

    Directory of Open Access Journals (Sweden)

    José Martínez

    1989-01-01

    Full Text Available

    Los mecanismos del da no celular en la insuficiencia renal aguda Incluyen alteraciones en la producción de energía, la permeabilidad celular y el transporte de calcio. Dichas alteraciones producen cambios progresivos en la estructura celular que pueden ser reversibles si desaparece la causa que llevó a la falla renal, excepto cuando se alcanza la fase final de la lesión de la membrana y se llega a necrosis celular. Este mismo fenómeno probablemente ocurre tambIén en situaciones clínicas.

    The mechanisms of cellular damage In acute renal failure Include alterations In energy production, cell membrane permeability and calcium transport. These changes lead to progressive damage of the whole cellular structure which In general can be reversible If the precipitating cause disappears, except when the final stages of cell membrane lesion take place and cellular necrosis has occurred. This phenomenon probably applies for the clinical settling as well.

  6. Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation.

    Science.gov (United States)

    Di Giusto, Gisela; Flamenco, Pilar; Rivarola, Valeria; Fernández, Juan; Melamud, Luciana; Ford, Paula; Capurro, Claudia

    2012-12-01

    We have previously demonstrated that in renal cortical collecting duct cells (RCCD(1)) the expression of the water channel Aquaporin 2 (AQP2) raises the rate of cell proliferation. In this study, we investigated the mechanisms involved in this process, focusing on the putative link between AQP2 expression, cell volume changes, and regulatory volume decrease activity (RVD). Two renal cell lines were used: WT-RCCD(1) (not expressing aquaporins) and AQP2-RCCD(1) (transfected with AQP2). Our results showed that when most RCCD(1) cells are in the G(1)-phase (unsynchronized), the blockage of barium-sensitive K(+) channels implicated in rapid RVD inhibits cell proliferation only in AQP2-RCCD(1) cells. Though cells in the S-phase (synchronized) had a remarkable increase in size, this enhancement was higher and was accompanied by a significant down-regulation in the rapid RVD response only in AQP2-RCCD(1) cells. This decrease in the RVD activity did not correlate with changes in AQP2 function or expression, demonstrating that AQP2-besides increasing water permeability-would play some other role. These observations together with evidence implying a cell-sizing mechanism that shortens the cell cycle of large cells, let us to propose that during nutrient uptake, in early G(1), volume tends to increase but it may be efficiently regulated by an AQP2-dependent mechanism, inducing the rapid activation of RVD channels. This mechanism would be down-regulated when volume needs to be increased in order to proceed into the S-phase. Therefore, during cell cycle, a coordinated modulation of the RVD activity may contribute to accelerate proliferation of cells expressing AQP2. Copyright © 2012 Wiley Periodicals, Inc.

  7. Chromophobe renal cell carcinoma: Comprehensive analysis of 11 cases

    Directory of Open Access Journals (Sweden)

    Rajendra B Nerli

    2015-01-01

    Full Text Available Background: Chromophobe renal cell carcinoma (chRCC is a subtype of RCC. chRCC is diagnosed mainly in sixth decade of life. An incidence of chRCC is similar in both men and woman. Eighty-six percent of chRCCs cases are diagnosed in early stages. To analyze the clinical behavior of chRCC, we retrospectively evaluated the data from our hospital. The aim of this study was to evaluate the incidence, clinical presentation, prognosis, and clinical outcome of chRCC in a retrospective series of nephrectomy specimens. Materials and Methods: We retrospectively looked at our hospital database, which included 318 patients who had undergone surgery for RCC between January 2000 and December 2013. Several parameters were noted in each patient, which included age, sex, symptoms at presentation, Eastern Cooperative Oncology Group performance status, tumor diameter, tumor node metastasis stage and grade, histologic cell type, follow-up time, local recurrence, disease progression, and death. Results: Of 318 patients included in the database, 11 (3.45% had chRCC. Preoperatively, 9 (81% had T1 lesions, and the remaining 2 (18.9% had T2 lesions. Of the T1 lesions, 6 had tumors ≤4 cm (T1a in diameter and the remaining 3 had tumors >4 cm (T1b in diameter. The mean survival of the patients was 99.27 ΁ 27 months. Conclusions: Our series confirms a favorable outcome for the chRCC subtype with little local aggressiveness and a low propensity for progression and death from cancer.

  8. H-ras-transformed NRK-52E renal epithelial cells have altered growth, morphology, and cytoskeletal structure that correlates with renal cell carcinoma in vivo.

    Science.gov (United States)

    Best, C J; Tanzer, L R; Phelps, P C; Merriman, R L; Boder, G G; Trump, B F; Elliget, K A

    1999-04-01

    We studied the effect of the ras oncogene on the growth kinetics, morphology, cytoskeletal structure, and tumorigenicity of the widely used NRK-52E rat kidney epithelial cell line and two H-ras oncogene-transformed cell lines, H/1.2-NRK-52E (H/1.2) and H/6.1-NRK-52E (H/6.1). Population doubling times of NRK-52E, H/1.2, and H/6.1 cells were 28, 26, and 24 h, respectively, with the transformed cells reaching higher saturation densities than the parent cells. NRK-52E cells had typical epithelial morphology with growth in colonies. H/1.2 and H/6.1 cell colonies were more closely packed, highly condensed, and had increased plasma membrane ruffling compared to parent cell colonies. NRK-52E cells showed microfilament, microtubule, and intermediate filament networks typical of epithelial cells, while H/1.2 and H/6.1 cells showed altered cytoskeleton architecture, with decreased stress fibers and increased microtubule and intermediate filament staining at the microtubule organizing center. H/1.2 and H/6.1 cells proliferated in an in vitro soft agar transformation assay, indicating anchorage-independence, and rapidly formed tumors in vivo with characteristics of renal cell carcinoma, including mixed populations of sarcomatoid, granular, and clear cells. H/6.1 cells consistently showed more extensive alterations of growth kinetics, morphology, and cytoskeleton than H/1.2 cells, and formed tumors of a more aggressive phenotype. These data suggest that analysis of renal cell characteristics in vitro may have potential in predicting tumor behavior in vivo, and significantly contribute to the utility of these cell lines as in vitro models for examining renal epithelial cell biology and the role of the ras proto-oncogene in signal transduction involving the cytoskeleton.

  9. Renal cell carcinoma in pregnancy: Still a management challenge

    Directory of Open Access Journals (Sweden)

    I.C. Akpayak

    2015-09-01

    Conclusion: Renal malignancy though rare in pregnancy can however occur. The key treatment is radical nephrectomy. Offering this very invasive treatment and getting patient to accept the treatment at any stage of pregnancy is difficult.

  10. Splenic and portal vein thrombosis in pancreatic metastasis from Renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Loos Martin

    2006-05-01

    Full Text Available Abstract Background Pancreatic metastases from previously treated renal cell carcinoma are uncommon. Surgical resection of pancreatic metastasis remains the only worthwhile modality of treatment. Case presentation A case where pancreatic metastasis from previously resected right sided renal cell carcinoma was resected with a subtotal left pancreatectomy is described. An unusual feature was the presence of a large splenic vein tumor thrombus extending into the portal vein with associated portal hypertension. The patient underwent an uneventful portal vein resection with primary anastomosis. Conclusion This is possibly the first documented case of portal vein renal tumor thrombosis in a case of isolated pancreatic metastasis from previously operated renal cell carcinoma in published world surgical literature.

  11. The ISUP system of staging, grading and classification of renal cell neoplasia

    Directory of Open Access Journals (Sweden)

    Hemamali Samaratunga

    2014-07-01

    Full Text Available There have been significant changes in the staging, classification and grading of renal cell neoplasia in recent times. Major changes have occurred in our understanding of extra-renal extension by renal cell cancer and how gross specimens must be handled to optimally display extra-renal spread. Since the 1981 World Health Organization (WHO classification of renal tumors, in which only a handful of different entities were reported, many new morphological types have been described in the literature, resulting in 50 different entities reported in the 2004 WHO classification. Since 2004, further new entities have been recognized and reported necessitating an update of the renal tumor classification. There have also been numerous grading systems for renal cell carcinoma with Fuhrman grading, the most widely used system. In recent times, the prognostic value and the applicability of the Fuhrman grading system in practice has been shown to be, at best, suboptimal. To address these issues and to recommend reporting guidelines, the International Society of Urological Pathology (ISUP undertook a review of adult renal neoplasia through an international consensus conference in Vancouver in 2012. The conduct of the conference was based upon evidence from the literature and the current practice amongst recognized experts in the field. Working groups selected to deal with key topics evaluated current data and identified points of controversy. A pre-meeting survey of the ISUP membership was followed by the consensus conference at which a formal ballot was taken on each key issue. A 65% majority vote was taken as consensus. This review summarizes the outcome and recommendations of this conference with regards to staging, classification and grading of renal cell neoplasia.

  12. The ISUP system of staging, grading and classification of renal cell neoplasia.

    Science.gov (United States)

    Samaratunga, Hemamali; Gianduzzo, Troy; Delahunt, Brett

    2014-01-01

    There have been significant changes in the staging, classification and grading of renal cell neoplasia in recent times. Major changes have occurred in our understanding of extra-renal extension by renal cell cancer and how gross specimens must be handled to optimally display extra-renal spread. Since the 1981 World Health Organization (WHO) classification of renal tumors, in which only a handful of different entities were reported, many new morphological types have been described in the literature, resulting in 50 different entities reported in the 2004 WHO classification. Since 2004, further new entities have been recognized and reported necessitating an update of the renal tumor classification. There have also been numerous grading systems for renal cell carcinoma with Fuhrman grading, the most widely used system. In recent times, the prognostic value and the applicability of the Fuhrman grading system in practice has been shown to be, at best, suboptimal. To address these issues and to recommend reporting guidelines, the International Society of Urological Pathology (ISUP) undertook a review of adult renal neoplasia through an international consensus conference in Vancouver in 2012. The conduct of the conference was based upon evidence from the literature and the current practice amongst recognized experts in the field. Working groups selected to deal with key topics evaluated current data and identified points of controversy. A pre-meeting survey of the ISUP membership was followed by the consensus conference at which a formal ballot was taken on each key issue. A 65% majority vote was taken as consensus. This review summarizes the outcome and recommendations of this conference with regards to staging, classification and grading of renal cell neoplasia.

  13. In vitro transformation of rat renal cells by treatment with ferric nitrilotriacetate.

    Directory of Open Access Journals (Sweden)

    Kakehashi C

    2001-04-01

    Full Text Available Administration of ferric nitrilotriacetate (Fe-NTA in vivo causes acute renal tubular injury and finally induces renal cell carcinoma. There is accumulating evidence that these processes involve free radicals generated by Fe-NTA. To study the mechanism of renal carcinogenesis by Fe-NTA, we attempted to induce malignant transformation of primary cultured renal cells by treatment with Fe-NTA. When primary cultured renal cells (PRC were treated continuously with Fe-NTA, all of the PRC died without transformation. On the other hand, when PRC were treated intermittently with Fe-NTA, transformed epithelial colonies were observed at 3 weeks after the first treatment. The established transformed cell line (RK523 showed drastic morphological transformation, grew in soft agar, and formed tumors when transplanted into athymic nude mice. These results indicate that the balance between cytotoxicity and mutagenecity is important for Fe-NTA induced transformation. The RK523 cell line may be a useful model for studying renal carcinogenesis in vitro.

  14. Effects of phlebotomy on the growth of ferric nitrilotriacetate-induced renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Mizote A

    2002-08-01

    Full Text Available The ferric nitrilotriacetate-induced carcinogenesis model is unique in that reactive oxygen species-free radicals are involved in the carcinogenic process. But the effects of iron-withdrawal in the progression of renal cell carcinoma are not well understood. We performed repeated phlebotomies on animals that had been administered ferric nitrilotriacetate in the initiation stage of renal cell carcinoma (phlebotomy group, and compared the development of renal tumors with those not receiving repeated phlebotomies (non-phlebotomy group. Ferric nitrilotriacetate-treated male Wistar rats were randomly divided into 2 groups: a phlebotomy group (21 rats and a non-phlebotomy group (17 rats. Ten age-adjusted normal rats were also observed as a normal group. Hematocrit was maintained under 25% in the phlebotomy group. Hematocrit levels in the normal group and in the non-phlebotomy group were not significantly different. As a result, the incidence of renal cell carcinoma was not significantly different between phlebotomy and non-phlebotomy animals. However, the total weight of the renal cell carcinoma was significantly heavier in the animals from non-phlebotomy group than in those from the phlebotomy group (23.64 g +/- 18.54 vs. 54.40 g +/- 42.40, P < 0.05. The present study demonstrated that phlebotomy after the administration of ferric nitrilotriacetate did not reduce the incidence of renal cell carcinoma. In addition, we showed that iron withdrawal at the promotion stage of carcinogenesis will retard tumor growth.

  15. Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Fernando G. Abarzua-Cabezas

    2015-02-01

    Full Text Available Purpose To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. Materials and Methods We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR was calculated according to the Modification of Diet in Renal Disease equation. Results The majority (85% of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%. Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months. Conclusion While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

  16. Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features.

    Science.gov (United States)

    Lu, Qing; Li, Cui-xian; Huang, Bei-jian; Xue, Li-yun; Wang, Wen-ping

    2015-02-01

    To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p quantitative analysis, RT and TTP were much shorter in ccRCCs than those in EAMLs and TAMLs. However, all these qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p 97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.

  17. Angiomotin promotes renal epithelial and carcinoma cell proliferation by retaining the nuclear YAP.

    Science.gov (United States)

    Lv, Meng; Li, Shuting; Luo, Changqin; Zhang, Xiaoman; Shen, Yanwei; Sui, Yan Xia; Wang, Fan; Wang, Xin; Yang, Jiao; Liu, Peijun; Yang, Jin

    2016-03-15

    Renal cell carcinoma (RCC) is one of the common tumors in the urinary system without effective therapies. Angiomotin (Amot) can interact with Yes-associated protein (YAP) to either stimulate or inhibit YAP activity, playing a potential role in cell proliferation. However, the role of Amot in regulating the proliferation of renal epithelial and RCC cells is unknown. Here, we show that Amot is expressed predominantly in the nucleus of RCC cells and tissues, and in the cytoplasm and nucleus of renal epithelial cells and paracancerous tissues. Furthermore, Amot silencing inhibited proliferation of HK-2 and 786-O cells while Amot upregulation promoted proliferation of ACHN cells. Interestingly, the location of Amot and YAP in RCC clinical samples and cells was similar. Amot interacted with YAP in HK-2 and 786-O cells, particularly in the nucleus. Moreover, Amot silencing mitigated the levels of nuclear YAP in HK-2 and 786-O cells and reduced YAP-related CTGF and Cyr61 expression in 786-O cells. Amot upregulation slightly increased the nuclear YAP and YAP-related gene expression in ACHN cells. Finally, enhanced YAP expression restored proliferation of Amot-silencing 786-O cells. Together, these data indicate that Amot is crucial for the maintenance of nuclear YAP to promote renal epithelial and RCC proliferation.

  18. Interferon-Gamma-Induced Nitric Oxide Inhibits the Proliferation of Murine Renal Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    David J. Tate Jr., John R. Patterson, Cruz Velasco-Gonzalez, Emily N. Carroll, Janie Trinh, Daniel Edwards, Ashok Aiyar, Beatriz Finkel-Jimenez, Arnold H. Zea

    2012-01-01

    Full Text Available Renal cell carcinoma (RCC remains one of the most resistant tumors to systemic chemotherapy, radiotherapy, and immunotherapy. Despite great progress in understanding the basic biology of RCC, the rate of responses in animal models and clinical trials using interferons (IFNs has not improved significantly. It is likely that the lack of responses can be due to the tumor's ability to develop tumor escape strategies. Currently, the use of targeted therapies has improved the clinical outcomes of patients with RCC and is associated with an increase of Th1-cytokine responses (IFNγ, indicating the importance of IFNγ in inhibiting tumor proliferation. Thus, the present study was designed to investigate a new mechanism by which IFNγ mediates direct anti-proliferative effects against murine renal cell carcinoma cell lines. When cultured RCC cell lines were exposed to murine recombinant IFNγ, a dose dependent growth inhibition in CL-2 and CL-19 cells was observed; this effect was not observed in Renca cells. Growth inhibition in CL-2 and CL-19 cell lines was associated with the intracellular induction of nitric oxide synthase (iNOS protein, resulting in a sustained elevation of nitric oxide (NO and citrulline, and a decrease in arginase activity. The inhibition of cell proliferation appears to be due to an arrest in the cell cycle. The results indicate that in certain RCC cell lines, IFNγ modulates L-arginine metabolism by shifting from arginase to iNOS activity, thereby developing a potent inhibitory mechanism to encumber tumor cell proliferation and survival. Elucidating the cellular events triggered by IFNγ in murine RCC cell lines will permit anti-tumor effects to be exploited in the development of new combination therapies that interfere with L-arginine metabolism to effectively combat RCC in patients.

  19. Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age : implications for surveillance

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Badeloe, Sadhanna; Oosting, Sjoukje F.; Hovenga, Sjoerd; Semmelink, Harry J. F.; van Moorselaar, R. Jeroen A.; van Waesberghe, Jan Hein; Mensenkamp, Arjen R.; Menko, Fred H.

    2012-01-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation

  20. Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance

    NARCIS (Netherlands)

    Spaendonck-Zwarts, K.Y. van; Badeloe, S.; Oosting, S.F.; Hovenga, S.; Semmelink, H.J.; Moorselaar, R.J. van; Waesberghe, J.H. van; Mensenkamp, A.R.; Menko, F.H.

    2012-01-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation

  1. Polycystin-1 Induces Cell Migration by Regulating Phosphatidylinositol 3-kinase-dependent Cytoskeletal Rearrangements and GSK3β-dependent Cell–Cell Mechanical Adhesion

    Science.gov (United States)

    Boca, Manila; D'Amato, Lisa; Distefano, Gianfranco; Polishchuk, Roman S.; Germino, Gregory G.

    2007-01-01

    Polycystin-1 (PC-1) is a large plasma-membrane receptor encoded by the PKD1 gene mutated in autosomal dominant polycystic kidney disease (ADPKD). Although the disease is thought to be recessive on a molecular level, the precise mechanism of cystogenesis is unclear, although cytoarchitecture defects seem to be the most likely initiating events. Here we show that PC-1 regulates the actin cytoskeleton in renal epithelial cells (MDCK) and induces cell scattering and cell migration. All of these effects require phosphatidylinositol 3-kinase (PI3-K) activity. Consistent with these observations Pkd1−/− mouse embryonic fibroblasts (MEFs) have reduced capabilities to migrate compared with controls. PC-1 overexpressing MDCK cells are able to polarize normally with proper adherens and tight junctions formation, but show quick reabsorption of ZO-1, E-cadherin, and β-catenin upon wounding of a monolayer and a transient epithelial-to-mesenchymal transition (EMT) that favors a rapid closure of the wound and repolarization. Finally, we show that PC-1 is able to control the turnover of cytoskeletal-associated β-catenin through activation of GSK3β. Expression of a nondegradable form of β-catenin in PC-1 MDCK cells restores strong cell–cell mechanical adhesion. We propose that PC-1 might be a central regulator of epithelial plasticity and its loss results in impaired normal epithelial homeostasis. PMID:17671167

  2. (1)H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava; Cormier, Kevin; Touaibia, Mohamed; Reyjal, Julie; Robichaud, Sarah; Belbraouet, Mehdi; Turcotte, Sandra

    2016-05-15

    Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors.

  3. Chronic lymphocytic lymphoma and concomitant renal cell carcinoma (Clear Cell Type: Review of the literature

    Directory of Open Access Journals (Sweden)

    Burak Uz

    2016-01-01

    Full Text Available In the present report, a 73 years-old male patient who developed clear cell type renal cell carcinoma (RCC 5 years after the diagnosis of chronic lymphocytic lymphoma (CLL and plausible explanations for this association were discussed by the authors. The incidence of CLL and RCC occurring in the same patient is higher than that expected in the general population. Various explicative hypotheses of this concurrence include treatment-related development of a second malignancy, immunomodulatory mechanisms, viral aetiology, cytokine (interleukin 6 release from a tumor, and common genetic mutations. Further investigations are warranted.

  4. Anti-T-cell antibodies for the treatment of acute rejection after renal transplantation.

    NARCIS (Netherlands)

    Hoogen, M.W.F. van den; Hoitsma, A.J.; Hilbrands, L.B.

    2012-01-01

    INTRODUCTION: Given the central role of T cells in the alloimmune response, anti-T-cell antibodies retain a prominent place in the treatment of renal allograft rejection. During the past decades, many anti-T-cell antibodies have emerged and subsequently left the field of solid organ transplantation,

  5. HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem-like Cells

    NARCIS (Netherlands)

    Nishizawa, Satoshi; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Takahashi, Akari; Tamura, Yasuaki; Mori, Takashi; Kanaseki, Takayuki; Kamiguchi, Kenjiro; Asanuma, Hiroko; Morita, Rena; Sokolovskaya, Alice; Matsuzaki, Junichi; Yamada, Ren; Fujii, Reona; Kampinga, Harm H.; Kondo, Toru; Hasegawa, Tadashi; Hara, Isao; Sato, Noriyuki

    2012-01-01

    Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB

  6. Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

    Directory of Open Access Journals (Sweden)

    Nadine Gelbrich

    2017-01-01

    Full Text Available Objective. Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods. Four renal cell cancer (RCC cell lines (Caki-1, 786-O, RCC4, and A498 and a nonmalignant renal cell line (RC-124 were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany, and expression profiles were compared. Results. Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion. This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.

  7. Salidroside reduces renal cell carcinoma proliferation by inhibiting JAK2/STAT3 signaling.

    Science.gov (United States)

    Lv, Cai; Huang, Yuan; Liu, Zhen-Xiang; Yu, Dan; Bai, Zhi-Ming

    2016-06-07

    Salidroside has been reported to exhibit anticancer properties. This study aimed to investigate the effects of salidroside on renal cell carcinoma growth. Cell viability and proliferation was assessed by Cell Counting Kit-8 and colony formation assays in A498 and 786-0 cells. The effects of salidroside on in vivo tumor growth were also assessed in a mouse xenograft model of renal cell carcinoma. Flow cytometry was used to analyze cell cycle and apoptosis and protein levels were determined by western blotting. Salidroside reduced cell viability and colony formation in both cell lines in a concentration- and time-dependent manner. Tumor growth was also suppressed in the mouse model. Furthermore, salidroside induced significant G1 phase cell cycle arrest and induced apoptosis in both A498 and 786-0 cells. Higher concentrations of salidroside reduced the levels of phosphorylated signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). These results suggested that salidroside produced potent anticancer properties in renal cell carcinoma by modulating JAK2/STAT3 signaling. Administration of salidroside to patients with renal cell carcinoma might provide a promising therapeutic strategy for this malignancy.

  8. Association between RASSF1A promoter methylation and renal cell cancer susceptibility: a meta-analysis.

    Science.gov (United States)

    Huang, Y Q; Guan, H; Liu, C H; Liu, D C; Xu, B; Jiang, L; Lin, Z X; Chen, M

    2016-04-25

    Epigenetic inactivation of Ras-associated domain family 1A (RASSF1A) by hyper-methylation of its promoter region has been identified in various cancers. However, the role of RASSF1A in renal cancer has neither been thoroughly investigated nor reviewed. In this study, we reviewed and performed a meta-analysis of 13 published studies reporting correlations between methylation frequency of the RASSF1A promoter region and renal cancer risk. The odds ratios (ORs) of eligible studies and their corresponding 95% confidence intervals (95%CIs) were used to correlate RASSF1A promoter methylation with renal cell cancer risk and clinical or pathological variables, respectively. RASSF1A promoter methylation was significantly associated with the risk of renal cell cancer (OR = 19.35, 95%CI = 9.57-39.13). RASSF1A promoter methylation was significantly associated with pathological tumor grade (OR = 3.32, 95%CI = 1.55-7.12), and a possible positive correlation between RASSF1A promoter methylation status and tumor stage was noted (OR = 1.89, 95%CI = 1.00-3.56, P = 0.051). Overall, this meta-analysis demonstrated that RASSF1A promoter methylation is significantly associated with increased risk of renal cell cancer. RASSF1A promoter methylation frequency was positively correlated with pathological tumor grade, but not the clinical stage. This study showed that RASSF1A promoter methylation could be utilized to predict renal cell cancer prognosis.

  9. Recurrence rates and survival in a Danish cohort with renal cell carcinoma

    DEFF Research Database (Denmark)

    Azawi, Nessn H; Tesfalem, Helen; Mosholt, Karina Sif Søndergaard;

    2016-01-01

    INTRODUCTION: Patients with localised and locally advanced renal cancer experience about 20% recurrence during a five-year follow-up period. The aim of the present study was to report recurrence rates and survival in a Danish population with renal cancer. METHODS: Data on patients diagnosed...... with renal cell carcinoma (RCC) at our institute from January 2005 to December 2013 were collected retrospectively. RESULTS: Overall, 367 patients were diagnosed with RCC during the period, and 78 patients (21%) presented with metastasis. The mean follow-up period for all patients was 41 months (standard...

  10. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels;

    2009-01-01

    PURPOSE: We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 121 consecutive patients...... neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P .... CONCLUSION: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC....

  11. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ronald M. Bukowski

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  12. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  13. Expression of CIDE proteins in clear cell renal cell carcinoma and their prognostic significance.

    Science.gov (United States)

    Yu, Ming; Wang, Hui; Zhao, Jun; Yuan, Yuan; Wang, Chao; Li, Jing; Zhang, Lijun; Zhang, Liying; Li, Qing; Ye, Jing

    2013-06-01

    Clear cell renal cell carcinoma (ccRCC) is the major and aggressive subtype of renal cell carcinoma. It is known to derive its histologic appearance from accumulation of abundant lipids and glycogens. The cell death-inducing DFF45-like effector (CIDE) family has been characterized as the lipid droplet proteins involved in the metabolism of lipid storage droplets. The purpose of this study was to evaluate the expression of CIDE proteins in ccRCC cells and to investigate their prognostic significance. We examined consecutive patients with sporadic ccRCC, who underwent nephrectomy, to measure their mRNA and protein expression of CIDE proteins. We found that Cidec and ADRP expression were significantly up-regulated in ccRCC, compared with normal kidney tissues. Cideb was down-regulated. We also found that Cideb was expressed more in low-grade ccRCC than in high-grade tumors. To further clarify the relationship between Cideb expression and patient prognosis, we evaluated 57 ccRCC patients followed up for 120 months. Reduced ccRCC Cideb expression was associated with a higher Fuhrman nuclear grade. Patients with high Cideb expression had better overall survival rate than those with low expression (p < 0.05). Cideb expression was an independent predictor of survival (p = 0.001). Although the biologic function of Cideb in ccRCC remains unknown, the expression level of Cideb might be a novel predictor of prognosis in ccRCC.

  14. An aggressive merkel cell carcinoma in a patient with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Sevda Gizlenti

    2014-12-01

    Full Text Available Merkel cell carcinoma (MCC is a rare cutaneous tumor arising from neuroendocrine cells and Merkel cells. Early diagnosis and treatment is important because of its aggressive course. We here report a 61 years old man with chronic renal failure, 3x5 cm mass on his right leg and inguinal-paraaortic lymph node metastases and resulting in death. MCC in the literature of the AIDS disease, organ transplantation, immunosuppressive therapy areas, and additional malignancies (multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and melanoma have been reported in patients with increased incidence. Up to date a patient with renal transplantation and Merkel cell carcinoma have been reported in the literature, Merkel cell carcinoma with chronic renal failure have not been reported.

  15. An atypical case of dermatomyositis associated with chromophobe renal cell carcinoma.

    Science.gov (United States)

    George, Michael David; Lahouti, Arash H; Christopher-Stine, Lisa

    2016-01-19

    Dermatomyositis and polymyositis are the major idiopathic inflammatory myopathies in adults. They are associated with an elevated risk of malignancy. However, renal tumours have rarely been described in dermatomyositis patients. We report the case of a 27-year-old Caucasian man with chromophobe renal cell cancer (ChRCC) and antinuclear matrix protein (NXP-2)-associated dermatomyositis. To the best of our knowledge, there are no previous reports of ChRCC presenting with dermatomyositis.

  16. Renal Cell Protection of Erythropoietin beyond Correcting The Anemia in Chronic Kidney Disease Patients

    OpenAIRE

    Hamid Nasri

    2013-01-01

    Currently many patients with chronic renal failure have profited from the use of erythropoietin to correct anemia (1,2). In chronic kidney disease, anemia is believed to be a surrogate index for tissue hypoxia that continues preexisting renal tissue injury (1-3). Erythropoietin is an essential glycoprotein that accelerates red blood cell maturation from erythroid progenitors and facilitates erythropoiesis. It is a 30.4 kD glycoprotein and class I cytokine containing 165 amino acids (3,4). App...

  17. Induction of trismus by sunitinib and pazopanib in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ridhima Iyer

    2017-01-01

    Full Text Available Tyrosine kinase inhibitors sunitinib and pazopanib are used as first-line agents in the treatment of metastatic renal cell carcinoma. Treatment-related toxicities have been described with both these drugs. This report describes a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is, to the best of our knowledge, the first such case to be reported.

  18. A case of renal cell carcinoma with an extensive inferior vena cava thrombosis

    Directory of Open Access Journals (Sweden)

    Majd Alfreijat

    2016-10-01

    Full Text Available Renal cell carcinoma (RCC is the most prevalent primary renal malignant neoplasm in adults. Most of the cases are usually found incidentally. It is commonly associated with venous thrombosis. We demonstrate a case of a RCC which was associated with an extensive thrombus that reached the upper part of the inferior vena cava (IVC. We also perform a brief literature review about the association between RCC and IVC thrombosis.

  19. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn;

    2008-01-01

    Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype...

  20. Adherence of uropathogenic Escherichia coli to human primary epithelial cells of renal pelvis

    Institute of Scientific and Technical Information of China (English)

    CHAO GU; JIN YING CHEN; MIN HOU; JING DONG HE; JI WU CHANG

    2006-01-01

    Human primary epithelial cells of renal pelvis was established to investigate the adherence of uropathogenic Escherichia coli (UPEC) to this cell line, in which the primary cell culture was performed by using cultivation of the normal epithelium of renal pelvis in keratinocyte serum free medium (K-SFM)with epidermal growth factor (EGF) and bovine pituitary extract (BPE). Both UPEC132 obtained from urine specimen of patients with pyelonephritis and the pilus-free representative strain E. coli K-12p678-54 were used to study the adherence of these strains on human primary epithelial cells of renal pelvis.The UPEC adherence was performed with observation on the morphological changes of the adhered cells,while the adhesion rates and indices were calculated in different times of experiment. In addition, the virulence genes hly and cnf1 of UPEC132 were detected by multiplex PCR assay. In this study, the human primary epithelial cells of renal pelvis was found to exhibit the character of the transitional epithelial cells. Compared with the control group, the adhesion rates and indices began to increase from 15 min of the experiment time and reached its peak in 120 min. The adhesion rate and index of UPEC132 to human primary epithelial cells of renal pelvis were 74.4% and 34.0 respectively. Many microscopic changes in the primary cells adhered with UPEC132 could be detected, such as rounding or irregularity in shape,unevenness in staining and the cytoplasmic and nuclear changes. It suggests that human primary epithelial cells of renal pelvis can be used for the experiment on UPEC adhesion, thus providing a basis for the further study on the pathogenesis of UPEC.

  1. Amygdalin inhibits the growth of renal cell carcinoma cells in vitro.

    Science.gov (United States)

    Juengel, Eva; Thomas, Anita; Rutz, Jochen; Makarevic, Jasmina; Tsaur, Igor; Nelson, Karen; Haferkamp, Axel; Blaheta, Roman A

    2016-02-01

    Although amygdalin is used by many cancer patients as an antitumor agent, there is a lack of information on the efficacy and toxicity of this natural compound. In the present study, the inhibitory effect of amygdalin on the growth of renal cell carcinoma (RCC) cells was examined. Amygdalin (10 mg/ml) was applied to the RCC cell lines, Caki-1, KTC-26 and A498, for 24 h or 2 weeks. Untreated cells served as controls. Tumor cell growth and proliferation were determined using MTT and BrdU tests, and cell cycle phases were evaluated. Expression of the cell cycle activating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1 and D3 as well as of the cell cycle inhibiting proteins p19 and p27 was examined by western blot analysis. Surface expression of the differentiation markers E- and N-cadherin was also investigated. Functional blockade by siRNA was used to determine the impact of several proteins on tumor cell growth. Amygdalin treatment caused a significant reduction in RCC cell growth and proliferation. This effect was correlated with a reduced percentage of G2/M-phase RCC cells and an increased percentage of cells in the G0/1-phase (Caki-1 and A498) or cell cycle arrest in the S-phase (KTC-26). Furthermore, amygdalin induced a marked decrease in cell cycle activating proteins, in particular cdk1 and cyclin B. Functional blocking of cdk1 and cyclin B resulted in significantly diminished tumor cell growth in all three RCC cell lines. Aside from its inhibitory effects on growth, amygdalin also modulated the differentiation markers, E- and N-cadherin. Hence, exposing RCC cells to amygdalin inhibited cell cycle progression and tumor cell growth by impairing cdk1 and cyclin B expression. Moreover, we noted that amygdalin affected differentiation markers. Thus, we suggest that amygdalin exerted RCC antitumor effects in vitro.

  2. Metastatic renal cell carcinoma of spleen diagnosed by fine-needle aspiration.

    Science.gov (United States)

    McGregor, Douglas H; Wu, Yaping; Weston, Allan P; McAnaw, Mary P; Bromfield, Cecil; Bhattatiry, Manu M

    2003-07-01

    Splenic metastases are infrequent, and determination of the primary site by fine-needle aspiration (FNA) can be complex. We report the case of a 65-year-old man who was found to have a large heterogeneously enhancing 8 x 7-inch splenic mass by abdominal computed tomography (CT). FNA by transesophageal endoscopic ultrasonography demonstrated atypical cells conclusive for malignancy and consistent with metastatic renal cell carcinoma based on cytomorphology, histochemical lipid positivity, and immunohistochemical positivity for cytokeratin, vimentin, and renal cell carcinoma marker. Repeat CT with and without arteriovenous contrast demonstrated bilateral renal cysts, including a 0.9 x 0.8-cm lesion on the left with significant enhancement. Splenectomy confirmed the radiological and cytological findings, and left kidney exploration and nephrectomy demonstrated a small (1.5 cm) lower pole renal cell carcinoma of chromophil (papillary) type, histologically similar to the splenic metastasis. This case demonstrates the diagnostic importance of interdisciplinary involvement (oncology, radiology, gastroenterology, pathology, and general and urologic surgery); cytomorphology; histochemistry, including fat stain on frozen cell block; and immunohistochemistry, including the recently developed renal cell carcinoma marker.

  3. Succinate Dehydrogenase B (SDHB): A New Prognostic Biomarker in Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    Cornejo, Kristine M.; Lu, Min; Yang, Ping; Wu, Shulin; Cai, Chao; Zhong, Wei-de; Olumi, Aria; Young, Robert H.; Wu, Chin-Lee

    2015-01-01

    Succinate dehydrogenase B (SDHB) is a mitochondrial enzyme complex subunit. Loss of SDHB protein expression has been found to correlate with SDHx gene mutations. Little is known about its expression in subtypes of renal cell carcinoma (RCC), and whether it’s a prognostic indicator. Four-hundred-fifty renal epithelial neoplasms were analyzed for SDHB, comprising of clear cell RCC (CCRCC) (n=240), papillary RCC (PRCC) (n=84), chromophobe RCC (ChRCC) (n=49), renal oncocytoma (RO) (n=47), clear cell papillary RCC (CCPRCC) (n=19) and von Hippel Lindau (VHL)- associated CCPRCC-like tumors (n=11). SDHB expression was graded based upon staining intensity using a 4-tiered system (0–3+), in which 3+ was strongest and complete absence was 0. Neoplasms were further categorized based upon staining extent into SDHB-weak (1–2+) and strong (3+). SDHB was strongly preserved in 131/240 (55%) CCRCCs, 84/84 (100%) PRCCs, 49/49 (100%) ChRCCs, 1/19 (5%) CCPRCC, 5/11 (45%) VHL-associated CCPRCC-like tumors and 47/47 (100%) ROs. The remaining 109 CCRCCs (45%), 18 CCPRCCs and 6 VHL-associated CCPRCC-like tumors had weak but preserved SDHB. SDHB expression in CCRCCs with high International Society of Urological Pathology (ISUP) nucleolar grade (G3-G4) correlated significantly with survival (log rank P=0.0004). SDHB is variably expressed in RCCs with clear cell morphology and strongly preserved in most other neoplasms. Therefore, weak staining, particularly in clear neoplasms, should not be misinterpreted as negative. Finally, SDHB expression in CCRCCs with high nucleolar grade (G3-G4) is significantly associated with survival, indicating it may be both a diagnostic and prognostic marker in RCC. PMID:25827535

  4. Renal cell carcinoma mimicking IgG4-related pseudotumor in autoimmune pancreatitis.

    Science.gov (United States)

    Khan, Muhammad Ali; Kamal, Sehrish; Ahmad, Usman; Chowdhury, Mohammed Andaleeb; Nawras, Ali

    2014-09-28

    Autoimmune pancreatitis is classified into two distinct clinical profiles. Type 1 autoimmune pancreatitis (AIP) is considered to be a manifestation of a novel clinicopathological entity called IgG4 related sclerosing disease, diagnosed using the Mayo Clinic HISORt criteria. Extra-pancreatic manifestations can include involvement of bile ducts, salivary gland, lung nodules, thyroiditis, tubulointerstitial nephritis, renal masses, and retroperitoneal fibrosis. Type 2 autoimmune pancreatitis on the other hand is confirmed by histologically seen duct centric pancreatitis without elevation of IgG4 or involvement of other organs. In type 1 autoimmune pancreatitis, extrapancreatic manifestations like bile duct strictures, tubulointerstitial nephritis, renal nodules, retroperitoneal fibrosis respond to steroid therapy. We present a case of type 1 autoimmune pancreatitis in which the renal mass did not respond to steroid therapy and was later on found to be renal cell carcinoma. To the best of our knowledge this is only the third reported case of autoimmune pancreatitis in which the patient had renal cell carcinoma. Our case highlights the importance of close follow up of lesions that do not respond to steroid treatment which in this case proved to be renal cell cancer.

  5. Renal Cell Carcinoma Mimicking Igg4-Related Pseudotumor in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan

    2014-09-01

    Full Text Available Context Autoimmune pancreatitis is classified into two distinct clinical profiles. Care report Type 1 autoimmunepancreatitis (AIP is considered to be a manifestation of a novel clinicopathological entity called IgG4 related sclerosingdisease, diagnosed using the Mayo Clinic HISORt criteria. Extra-pancreatic manifestations can include involvement of bileducts, salivary gland, lung nodules, thyroiditis, tubulointerstitial nephritis, renal masses, and retroperitoneal fibrosis. Type2 autoimmune pancreatitis on the other hand is confirmed by histologically seen duct centric pancreatitis without elevationof IgG4 or involvement of other organs. In type 1 autoimmune pancreatitis, extrapancreatic manifestations like bile ductstrictures, tubulointerstitial nephritis, renal nodules, retroperitoneal fibrosis respond to steroid therapy. Conclusion Wepresent a case of type 1 autoimmune pancreatitis in which the renal mass did not respond to steroid therapy and was later on found to be renal cell carcinoma. To the best of our knowledge this is only the third reported case of autoimmune pancreatitis in which the patient had renal cell carcinoma. Our case highlights the importance of close follow up of lesions that do not respond to steroid treatment which in this case proved to be renal cell cancer.

  6. Prognostic impact of in vivo soluble cell adhesion molecules in metastatic renal cell carcinoma.

    Science.gov (United States)

    Hoffmann, R; Franzke, A; Buer, J; Sel, S; Oevermann, K; Duensing, A; Probst, M; Duensing, S; Kirchner, H; Ganser, A; Atzpodien, J

    1999-04-01

    The purpose of the study was to determine prognostic significance of pretreatment serum levels of different molecules involved in cell to cell interactions along with other clinical parameters in patients with metastatic renal cell carcinoma. sICAM-1, sVCAM-1 and sELAM-1 serum levels were determined by ELISA assays in sera from 99 patients with histologically confirmed progressive metastatic renal cell carcinoma prior to initiation of systemic therapy. Kaplan-Meier survival analysis, log-rank statistics and two-proportional Cox regression analyses were employed to identify risk factors and to demonstrate statistical independence. In univariate analyses, the following pretreatment risk factors could be identified: serum sICAM-1 level > 360 ng ml(-1), erythrocyte sedimentation rate > 70 mm h(-1), serum C-reactive protein level > 8 mg l(-1), serum lactic dehydrogenase level > 240 U/l and neutrophil count > 6000 microl(-1). Multivariate analyses demonstrated statistical independence for serum sICAM-1 level, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level as pretreatment predictors of overall patient survival. The prognostic significance of sICAM-1 might indicate a role of this molecule for tumour progression, potentially in association with the abrogation of anti-tumour immune responses. The possibility of defining a pretreatment risk model based on sICAM-1 level, ESR and CRP also warrants further investigation, with regard to a possible linkage between acute phase proteins and sICAM-1 levels.

  7. Expression of insulin-like growth factor family genes in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ryszard Braczkowski

    2016-06-01

    Full Text Available Aim of the study : Despite significant progress in the pathology of clear cell renal cell carcinoma (ccRCC, diagnostic and predictive factors of major importance have not been discovered. Some hopes are associated with insulin-like growth factors. The aim of the study was to compare the expression of genes for insulin-like growth factor family in tumours and in tissue of kidneys without cancer. Material and methods : Fifty-two patients years with clear cell renal cell cancer were qualified to the study group; patients nephrectomised because of hydronephrosis were included in the control group. Expression of genes were evaluated by RT-PCR. Results : Expression of IGFR-1 gene in tumour accounts for about 60% of cases. The incidence is higher than in corresponding adjacent non-cancerous kidney tissues and higher (but with no statistical significance than in kidney without cancer. Expression of IGFR-2 gene in tumours has not been established. The incidence of the expression in corresponding adjacent non-cancerous kidney tissues is small. Expression of this gene has been present in all specimens from kidneys without cancer. Expression of IGFBP-3 gene ascertained in all (except four cases of ccRCC and in the majority of clippings from adjacent tissue. It was not found in kidneys from the control group. IGF-1, IGF-2, and IGFR-1 mRNA copy numbers in ccRCC were higher than in the material from the control group

  8. Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells.

    Science.gov (United States)

    Khan, Mohammed I; Czarnecka, Anna M; Lewicki, Sławomir; Helbrecht, Igor; Brodaczewska, Klaudia; Koch, Irena; Zdanowski, Robert; Król, Magdalena; Szczylik, Cezary

    2016-01-01

    Recent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells-stem cell-like cancer cells (SCLCCs)-which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells. The main goal of the project was to describe the gene-expression profile of stem cell-like cancer cells of primary tumor and metastatic origin. Real-time PCR analysis of stemness genes (Oct-4, Nanog and Ncam) and soft agar colony formation assay were conducted to check the stemness properties of renal cell carcinoma (RCC) cell lines. FACS analysis of CD105+ and CD133+ cells was performed on RCC cells. Isolated CD105+ cells were verified for expression of mesenchymal markers-CD24, CD146, CD90, CD73, CD44, CD11b, CD19, CD34, CD45, HLA-DR and alkaline phosphatase. Hanging drop assay was used to investigate CD105+ cell-cell cohesion. Analysis of free-floating 3D spheres formed by isolated CD105+ was verified, as spheres have been hypothesized to contain undifferentiated multipotent progenitor cells. Finally, CD105+ cells were sorted from primary (Caki-2) and metastatic (ACHN) renal cell cancer cell lines. Gene-expression profiling of sorted CD105+ cells was performed with Agilent's human GE 4x44K v2 microarrays. Differentially expressed genes were further categorized into canonical pathways. Network analysis and downstream analysis were performed with Ingenuity Pathway Analysis. Metastatic RCC cell lines (ACHN and Caki-1) demonstrated higher colony-forming ability in comparison to primary RCC cell lines. Metastatic RCC cell lines harbor numerous CD105+ cell subpopulations and have

  9. Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps.

    Directory of Open Access Journals (Sweden)

    Vu Tran

    Full Text Available Transepithelial potential (TEP is the voltage across a polarized epithelium. In epithelia that have active transport functions, the force for transmembrane flux of an ion is dictated by the electrochemical gradient in which TEP plays an essential role. In epithelial injury, disruption of the epithelial barrier collapses the TEP at the wound edge, resulting in the establishment of an endogenous wound electric field (∼100 mV/mm that is directed towards the center of the wound. This endogenous electric field is implicated to enhance wound healing by guiding cell migration. We thus seek techniques to enhance the TEP, which may increase the wound electric fields and enhance wound healing. We report a novel technique, termed synchronization modulation (SM using a train of electric pulses to synchronize the Na/K pump activity, and then modulating the pumping cycles to increase the efficiency of the Na/K pumps. Kidney epithelial monolayers (MDCK cells maintain a stable TEP and transepithelial resistance (TER. SM significantly increased TEP over four fold. Either ouabain or digoxin, which block Na/K pump, abolished SM-induced TEP increases. In addition to the pump activity, basolateral distribution of Na/K pumps is essential for an increase in TEP. Our study for the first time developed an electrical approach to significantly increase the TEP. This technique targeting the Na/K pump may be used to modulate TEP, and may have implication in wound healing and in diseases where TEP needs to be modulated.

  10. Prolactin and dopamine 1-like receptor interaction in renal proximal tubular cells.

    Science.gov (United States)

    Crambert, Susanne; Sjöberg, Agneta; Eklöf, Ann-Christine; Ibarra, Fernando; Holtbäck, Ulla

    2010-07-01

    Prolactin is a natriuretic hormone and acts by inhibiting the activity of renal tubular Na(+)-K(+)-ATPase activity. These effects require an intact renal dopamine system. Here, we have studied by which mechanism prolactin and dopamine interact in Sprague-Dawley rat renal tissue. Na(+)-K(+)-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected renal proximal tubular segments. Intracellular signaling