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https://www.readbyqxmd.com/read/28350874/snon-upregulation-ameliorates-renal-fibrosis-in-diabetic-nephropathy
#1
Lirong Liu, Mingjun Shi, Yuanyuan Wang, Changzhi Zhang, Bo Su, Ying Xiao, Bing Guo
Progressive reduction of SnoN is associated with gradual elevation of TGF-β1 during diabetic nephropathy progression, suggesting SnoN to be a possible mediator of TGF-β1 signaling, with potential therapeutic benefits against TGF- β1 -induced renal fibrosis. To characterize SnoN for its role in renal fibrosis, we assessed SnoN expression patterns in response to high glucose stress, and evaluated the effects of upregulating SnoN on renal fibrosis. High glucose stress induced significantly elevated SnoN, TGF-β1, and Arkadia transcription; however, significantly reduced SnoN protein levels were observed under these conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28350788/ldl-cholesterol-counteracts-the-antitumour-effect-of-tyrosine-kinase-inhibitors-against-renal-cell-carcinoma
#2
Sei Naito, Peter Makhov, Igor Astsaturov, Konstantin Golovine, Alexei Tulin, Alexander Kutikov, Robert G Uzzo, Vladimir M Kolenko
BACKGROUND: Treatment with tyrosine kinase inhibitors (TKIs) significantly improves survival of patients with renal cell carcinoma (RCC). However, about one-quarter of the RCC patients are primarily refractory to treatment with TKIs. METHODS: We examined viability of RCC and endothelial cells treated with low-density lipoprotein (LDL) and/or TKIs. Next, we validated the potential role of PI3K/AKT signalling in LDL-mediated TKI resistance. Finally, we examined the effect of a high-fat/high-cholesterol diet on the response of RCC xenograft tumours to sunitinib...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28346435/aav9-mediated-engineering-of-autotransplanted-kidney-of-non-human-primates
#3
S Tomasoni, P Trionfini, N Azzollini, L Zentilin, M Giacca, S Aiello, L Longaretti, E Cozzi, N Baldan, G Remuzzi, A Benigni
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic anti-rejection therapy. Gene delivery of the immunomodulatory protein CTLA4-Ig prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here, we generated AAV2 and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346348/vitamin-d-in-chronic-kidney-disease-and-dialysis-patients
#4
REVIEW
Guillaume Jean, Jean Claude Souberbielle, Charles Chazot
Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue...
March 25, 2017: Nutrients
https://www.readbyqxmd.com/read/28346230/glutaminase-and-poly-adp-ribose-polymerase-inhibitors-suppress-pyrimidine-synthesis-and-vhl-deficient-renal-cancers
#5
Arimichi Okazaki, Paulo A Gameiro, Danos Christodoulou, Laura Laviollette, Meike Schneider, Frances Chaves, Anat Stemmer-Rachamimov, Stephanie A Yazinski, Richard Lee, Gregory Stephanopoulos, Lee Zou, Othon Iliopoulos
Many cancer-associated mutations that deregulate cellular metabolic responses to hypoxia also reprogram carbon metabolism to promote utilization of glutamine. In renal cell carcinoma (RCC), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate citrate and lipids through reductive carboxylation (RC) of α-ketoglutarate (αKG). Glutamine can also generate aspartate, the carbon source for pyrimidine biosynthesis, and glutathione for redox balance. Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintain de novo pyrimidine biosynthesis...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346124/pax8-napsin-a-and-cd10-as-immunohistochemical-markers-of-canine-renal-cell-carcinoma
#6
Tyler J Peat, Elijah F Edmondson, Margaret A Miller, Dee M DuSold, José A Ramos-Vara
Pax8, napsin A, and CD10 are useful immunohistochemical markers of human renal cell carcinoma (RCC); however, their diagnostic utility in canine RCC is unclear. Forty formalin-fixed paraffin-embedded renal cell carcinomas from dogs (15 papillary, 12 solid, and 13 tubular) and 10 metastases were evaluated for expression of Pax8, napsin A, and CD10. Thirty-nine (98%), 24 (60%), and 19 (50%) tumors expressed Pax8 (nuclear labeling), napsin A (cytoplasmic labeling), and CD10 (cytoplasmic and membranous labeling), respectively...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28345492/rasburicase-induced-methemoglobinemia-the-eyes-do-not-see-what-the-mind-does-not-know
#7
Uroosa Ibrahim, Amina Saqib, Farhan Mohammad, Jean Paul Atallah, Marcel Odaimi
Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#8
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344344/detecting-truly-clonal-alterations-from-multi-region-profiling-of-tumours
#9
Benjamin Werner, Arne Traulsen, Andrea Sottoriva, David Dingli
Modern cancer therapies aim at targeting tumour-specific alterations, such as mutations or neo-antigens, and maximal treatment efficacy requires that targeted alterations are present in all tumour cells. Currently, treatment decisions are based on one or a few samples per tumour, creating uncertainty on whether alterations found in those samples are actually present in all tumour cells. The probability of classifying clonal versus sub-clonal alterations from multi-region profiling of tumours depends on the earliest phylogenetic branching event during tumour growth...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344323/new-knowledge-of-the-mechanisms-of-sorafenib-resistance-in-liver-cancer
#10
REVIEW
Yan-Jing Zhu, Bo Zheng, Hong-Yang Wang, Lei Chen
Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma (HCC) in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems...
March 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28344130/aquaporin-3-deletion-in-mice-results-in-renal-collecting-duct-abnormalities-and-worsens-ischemia-reperfusion-injury
#11
Lei Lei, Weiling Wang, Yingli Jia, Limin Su, Hong Zhou, Alan S Verkman, Baoxue Yang
Aquaporin-3 (AQP3), a transporter of water, glycerol and H2O2, is expressed in basolateral membranes of principal cells in kidney collecting duct. Here, we report that AQP3 deletion in mice affects renal function and modulates renal injury. We found collecting duct hyperplasia and cell swelling in kidneys of adult AQP3 null mice. After mild renal ischemia-reperfusion (IR), AQP3 null mice had significantly greater blood urea nitrogen (57mg/dl) and creatinine (136μM) than wild-type mice (35mg/dl and 48μM, respectively), and showed renal morphological changes, including tubular dilatation, erythrocyte diapedesis and collecting duct incompletion...
March 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28343584/percutaneous-cryoablation-of-the-horseshoe-kidney-an-initial-experience
#12
Junjian Huang, Thomas D Atwell, A Nicholas Kurup, Stephen A Boorjian, R Houston Thompson, Grant D Schmit
Between June 2006 and January 2016, 6 renal cryoablation procedures were performed in 5 patients with horseshoe kidneys. Renal cell carcinoma (RCC) accounted for 5 of the tumors, and the sixth was a carcinoid tumor. All 6 procedures were technically successful. The patient with the carcinoid tumor developed local tumor progression 38 months after ablation. Technique effectiveness was achieved in all 5 patients with RCC. Two complications occurred: obstructive hematuria and transient inguinal neuralgia after ablation...
April 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28343356/development-of-a-novel-strategy-to-target-cd39-antithrombotic-activity-to-the-endothelial-platelet-microenvironment-in-kidney-ischemia-reperfusion-injury
#13
Maithili Sashindranath, Karen M Dwyer, Shala Dezfouli, Carly Selan, Sandra Crikis, Bo Lu, Yuping Yuan, Michael J Hickey, Karlheinz Peter, Simon C Robson, Peter J Cowan, Harshal H Nandurkar
Kidney ischemia-reperfusion injury (IRI) is common during transplantation. IRI is characterised by inflammation and thrombosis and associated with acute and chronic graft dysfunction. P-selectin and its ligand PSGL-1 are cell adhesion molecules that control leukocyte-endothelial and leukocyte-platelet interactions under inflammatory conditions. CD39 is the dominant vascular nucleotidase that facilitates adenosine generation via extracellular ATP/ADP-phosphohydrolysis. Adenosine signalling is protective in renal IRI, but CD39 catalytic activity is lost with exposure to oxidant stress...
March 25, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28343336/sunitinib-induced-hypothyroidism-predicts-progression-free-survival-in-metastatic-renal-cell-carcinoma-patients
#14
Anna Buda-Nowak, Jakub Kucharz, Paulina Dumnicka, Marek Kuzniewski, Roman Maria Herman, Aneta L Zygulska, Beata Kusnierz-Cabala
Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28343197/-skin-cancers-in-kidney-transplant-recipients
#15
Anna Bieryło, Szymon Brzósko, Elżbieta Laudańska, Beata Naumnik
Kidney transplantation is the best treatment for end-stage renal failure. It prolongs the patient's life, improves quality of life and reduces costs associated with renal replacement therapy. Increasingly, newer immunosuppressive regimens allow for the proper functioning of the transplanted organ for many years. The progress in transplantation, qualification patients in older age for the procedure and longer survival of kidney graft lead to an increase in the number of patients receiving immunosuppressive drugs...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28343003/essential-design-considerations-for-the-resazurin-reduction-assay-to-noninvasively-quantify-cell-expansion-within-perfused-extracellular-matrix-scaffolds
#16
Joseph S Uzarski, Michael D DiVito, Jason A Wertheim, William M Miller
Precise measurement of cellularity within bioartificial tissues and extracellular matrix (ECM) scaffolds is necessary to augment rigorous characterization of cellular behavior, as accurate benchmarking of tissue function to cell number allows for comparison of data across experiments and between laboratories. Resazurin, a soluble dye that is reduced to highly fluorescent resorufin in proportion to the metabolic activity of a cell population, is a valuable, noninvasive tool to measure cell number. We investigated experimental conditions in which resazurin reduction is a reliable indicator of cellularity within three-dimensional (3D) ECM scaffolds...
February 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/28342978/a-new-benzenediamine-derivative-modulates-toll-like-receptors-induced-myeloid-dendritic-cells-activation-and-ameliorates-lupus-like-syndrome-in-mrllpr-lpr-mice
#17
Sheng Gao, Yongsheng Gong, Jianjian Ji, Linbo Yuan, Liping Han, Yimin Guo, Xiaofang Fan, Yayi Hou, Chunyan Hua
Modulators of the over-activation of myeloid dendritic cells (mDCs) by Toll-like receptors (TLRs) have an advantage in the treatment of systemic lupus erythematosus (SLE). This study was designed to evaluate the effects of FC-99, a novel benzenediamine derivative, on TLR-induced activation of mDCs, and to assess the efficacy of FC-99 in a murine model of SLE. In vitro, FC-99 inhibited the phenotypic (CD40 and MHC-II) and functional activation (IL-12 and CXCL10) of mDCs induced by TLR ligands. In vivo, MRLlpr/lpr mice displayed renal diseases associated with increased levels of proteinuria and immunoglobulin, which were ameliorated by FC-99...
March 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28342931/clear-cell-renal-cell-carcinoma-with-extensive-osseous-metaplasia-report-of-a-rare-case
#18
Huixing Pan, Deyao Wu, Huaizhang Wang, Yan Pan, Ting Zhang, Jian Zhou
A 48-year-old Chinese woman presenting with continuing dull pain in the right lower back and abdomen was found to have a tumor with extensive osseous metaplasia in the the upper-middle pole of the right kidney. The exsected neoplasm specimen revealed a 29×26mm hard tumor with dense ossification. Histopathological examination of the tumor contained lamellar bone forming trabeculae intermingled and showed spherical or polygonal epithelial cells which contained slightly irregular nuclei with small nucleoli and abundant pink to clear cytoplasm...
March 22, 2017: Urology
https://www.readbyqxmd.com/read/28341816/increased-expression-of-toll-like-receptors-2-and-4-in-renal-transplant-recipients-that-develop-allograft-dysfunction-a-cohort-study
#19
Morteza Hosseinzadeh, Mohsen Nafar, Pedram Ahmadpoor, Farshid Noorbakhsh, Mir Saeed Yekaninejad, Mohammad Hossein Niknam, Aliakbar Amirzargar
BACKGROUND: The incidence of ischemic reperfusion injury (IRI) in early phase post-transplantation and activation of toll-like receptor (TLR-2) and TLR-4 remarkably impact the outcome of a renal allograft. OBJECTIVE: To investigate whether the expression of TLRs in peripheral blood mononuclear cells (PBMCs) can predict the clinical outcome of kidney allografts. METHODS: We obtained blood samples from 52 renal transplant patients before transplant, and 2, 90, and 180 days post-transplantation in order to analyze the surface expressions of TLR-2 and TLR-4 on peripheral blood monocytes...
March 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28341694/mineralocorticoid-receptor-and-nacl-transport-mechanisms-in-the-renal-distal-nephron
#20
Shigeru Shibata
A key role of aldosterone and mineralocorticoid receptor is to regulate fluid volume and K+ homeostasis in the body by acting on the renal distal nephron. Global responses of the kidney to elevated aldosterone levels are determined by the coordinate action of different constituent tubule cells, including principal cells, intercalated cells, and distal convoluted tubule cells. Recent studies on genetic mutations causing aldosterone overproduction have identified molecules involved in aldosterone biosynthesis in the adrenal gland, and there is also increasing evidence for mechanisms and signaling pathways regulating the balance between renal NaCl reabsorption and K+ secretion, the two major effects of aldosterone...
March 24, 2017: Journal of Endocrinology
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