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renal cancer model

Shin-Rong Lee, Georgios Gemenetzis, Michol Cooper, Ammar A Javed, John L Cameron, Christopher L Wolfgang, Frederick E Eckhauser, Jin He, Matthew J Weiss
PURPOSE: The goal of this study was to assess the outcomes and characteristics of patients who underwent pancreatectomy for metastatic disease to the pancreas. METHODS: Patients who underwent surgical resection of metastatic disease to the pancreas from 1988 to 2016 were identified using a prospectively maintained database. Data on clinicopathological features and outcomes of these patients were analyzed. Cox proportional hazard models were employed to identify patient-specific risk factors that influence survival...
October 21, 2016: Annals of Surgical Oncology
Jing Chen, Xiaoyan Zhang, Han Zhang, Tongqiang Liu, Hui Zhang, Jie Teng, Jun Ji, Xiaoqiang Ding
Chronic kidney disease (CKD) is a state of Klotho deficiency. The Klotho expression may be suppressed due to DNA hypermethylation in cancer cells so we have investigated the effects and possible mechanisms by which Klotho expression is regulated in human aortic smooth muscle cells (HASMCs). The vascular Klotho hypermethylation in radial arteries of patients with end-stage renal disease was described. Cultured HASMCs and 5/6-nephrectomized Sprague Dawley (SD) rats treated with indoxyl sulfate (IS) were used as in vitro and in vivo models, respectively...
2016: International Journal of Biological Sciences
Leandro Z Crivellenti, Gyl E B Silva, Sofia Borin-Crivellenti, Rachel Cianciolo, Christopher A Adin, Márcio Dantas, Denner S Dos Anjos, Mirela Tinucci-Costa, Aureo E Santana
The incidence and prevalence of paraneoplastic glomerulopathy, especially associated with carcinoma, are a matter of debate and the causal link between cancer and glomerular diseases remains unclear. The aim of this study was to evaluate renal biopsies of selected bitches with spontaneous mammary gland carcinoma. We hypothesized that dogs with mammary carcinomas would show histologic evidence of glomerular pathology. A prospective study was performed in dogs with naturally occurring mammary carcinoma that were undergoing tumor resection and ovariohysterectomy...
2016: PloS One
Nuray Erin, Tümay İpekçi, Bahar Akkaya, İrem Hicran Özbudak, Mehmet Baykara
Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC...
October 19, 2016: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
Fangzhou Shen, Jian Li, Ying Zhu, Zhuo Wang
Cancer cells have different metabolism in contrast to normal cells. The advancement in omics measurement technology enables the genome-wide characterization of altered cellular processes in cancers, but the metabolic flux landscape of cancer is still far from understood. In this study, we compared the well-reconstructed tissue-specific models of five cancers, including breast, liver, lung, renal, and urothelial cancer, and their corresponding normal cells. There are similar patterns in majority of significantly regulated pathways and enriched pathways in correlated reaction sets...
August 29, 2016: Journal of Bioinformatics and Computational Biology
Iris J H van Vlodrop, Sophie C Joosten, Tim de Meyer, Kim M Smits, Leander Van Neste, Veerle Melotte, Marcella Baldewijns, Leo J Schouten, Piet A van den Brandt, Jana Jeschke, Joo Mi Yi, Kornel Schuebel, Nita Ahuja, James G Herman, Maureen Aarts, Fred T Bosman, Wim Van Criekinge, Manon van Engeland
PURPOSE: The currently used prognostic models for patients with non-metastatic clear cell renal cell carcinoma (ccRCC) are based on clinicopathological features and might be improved by adding molecular markers. Epigenetic alterations occur frequently in ccRCC and are promising biomarkers. The aim of this study is to identify prognostic promoter methylation markers for ccRCC. EXPERIMENTAL DESIGN: We integrated data generated by massive parallel sequencing of methyl-binding domain enriched DNA and microarray based RNA expression profiling of 5-aza-2'-deoxycytidine treated ccRCC cell lines to comprehensively characterize the ccRCC methylome...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Masahiro Ono, Atsumi Baden, Hiroyuki Okudaira, Masato Kobayashi, Keiichi Kawai, Shuntaro Oka, Hirokatsu Yoshimura
[(18)F]Fluciclovine (trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid; anti-[(18)F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97-230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [(18)F]fluciclovine reuptake. [(14)C]Fluciclovine (trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid) was used because of its long half-life...
October 14, 2016: International Journal of Molecular Sciences
D Peng, X S Li, C J Zhang, K W Yang, Q Tang, L Zhang, X T Yu, Z S He, L Q Zhou
OBJECTIVE: To evaluate the impacts of clinical, pathological, and laboratory factors on oncological outcomes of patients with T3N0M0 renal cell carcinoma. METHODS: The clinical data, laboratory exam results, and follow-up outcomes of 182 patients with T3N0M0 renal cell carcinoma who underwent nephrectomy from 2007 to 2012 in Peking University First Hospital were retrospectively collected. The 5-year cancer-specific survival and 5-year recurrence-free survival of all the patients were calculated using Kaplan-Meier method, and the statistical significance between the survival curves were compared using the Log-rank test...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
James J Hsieh, David Chen, Patricia I Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H Huberman, Umesh Bhanot, Michael S Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H Won, Daoqi You, Agnes Viale, William Lee, A Ari Hakimi, Michael F Berger, Nicholas D Socci, Emily H Cheng, Jennifer Knox, Martin H Voss, Maurizio Voi, Robert J Motzer
BACKGROUND: Metastatic renal cell carcinoma (RCC) patients are commonly treated with vascular endothelial growth factor (VEGF) inhibitors or mammalian target of rapamycin inhibitors. Correlations between somatic mutations and first-line targeted therapy outcomes have not been reported on a randomized trial. OBJECTIVE: To evaluate the relationship between tumor mutations and treatment outcomes in RECORD-3, a randomized trial comparing first-line everolimus (mTOR inhibitor) followed by sunitinib (VEGF inhibitor) at progression with the opposite sequence in 471 metastatic RCC patients...
October 14, 2016: European Urology
Valentina Di Gialleonardo, Sui Seng Tee, Hannah N Aldeborgh, Vesselin Z Miloushev, Lidia S Cunha, George D Sukenick, Kayvan R Keshari
Nuclear magnetic resonance (NMR) spectroscopy is used in metabolomics to perform quantitative profiling of low-molecular weight compounds from biological specimens. The measurement of endogenous metabolites using NMR can identify new metabolic biomarkers in physiological and pathological conditions, and assess treatment response. In this study we present a rapid approach to indirectly quantify 13C enriched molecules using one-dimensional (1D) 1H NMR. We demonstrate this approach using isotopically labeled [1,6-13C]glucose and in 4 different cell lines...
October 17, 2016: Analytical Chemistry
Wenting Ma, Le Tao, Xuefei Wang, Qinyi Liu, Wei Zhang, Qiuying Li, Chunfeng He, Dongying Xue, Jie Zhang, Cheng Liu
AIMS: Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism. METHODS: Mice underwent UUO followed by vehicle or sorafenib treatment...
October 17, 2016: Cellular Physiology and Biochemistry
Thomas Ebenhan, Isabel Schoeman, Daniel D Rossouw, Anne Grobler, Biljana Marjanovic-Painter, Judith Wagener, Hendrik G Kruger, Mike M Sathekge, Jan Rijn Zeevaart
PURPOSE: Radiopharmaceuticals containing the motive tripeptide arginyl-glycyl-asparatic acid (RGD) are known to target ανβ3 integrins during tumor angiogenesis. A more generic kit radiolabeling procedure accommodating Ga-68 from different generators was developed for NOTA-RGD and evaluated for its versatile use and safety in subsequent in vivo applications. The [(68)Ga]NOTA-RGD kit was further verified for its expected biodistribution and pharmacokinetics in nonhuman primates and its clinical sensitivity to detect solitary pulmonary nodules (SPN) in cancer patients...
October 14, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Ernesto Zecca, Cinzia Brunelli, Paola Bracchi, Giuseppe Biancofiore, Carlo De Sangro, Roberto Bortolussi, Luigi Montanari, Marco Maltoni, Cecilia Moro, Ugo Colonna, Gabriele Finco, Maria Teresa Roy, Vittorio Ferrari, Oscar Alabiso, Giovanni Rosti, Stein Kaasa, Augusto Caraceni
: Context Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain but evidence about their relative tolerability has significant methodological limitations. OBJECTIVES: This study is mainly aimed at comparing the risk of developing adverse events (AEs) with controlled release oral morphine versus oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups...
October 11, 2016: Journal of Pain and Symptom Management
Isla S Mackenzie, Steven V Morant, Li Wei, Alastair M Thompson, Thomas M MacDonald
AIMS: Spironolactone is widely used to treat heart failure, hypertension and liver disease with increased usage in recent years. Spironolactone has endocrine effects that could influence cancer risks and historical reports suggest possible links with increased risk of certain types of cancer. The aim of this study was to assess the effect of spironolactone exposure on cancer incidence. METHODS: A pharmacoepidemiological propensity score-matched cohort study was performed to assess the effect of spironolactone exposure on cancer incidence...
October 13, 2016: British Journal of Clinical Pharmacology
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
Hannah L Bader, Tien Hsu
BACKGROUND: Mutations in the tumor suppressor gene von Hippel-Lindau (VHL) underlie a hereditary cancer syndrome-VHL disease-and are also frequently observed in sporadic renal cell carcinoma of the clear cell type (ccRCC). VHL disease is characterized by malignant and benign tumors in a few specific tissues, including ccRCC, hemangioblastoma and pheochromocytoma. The etiology of these tumors remains unresolved. METHODS: Conditional inactivation of the VHL gene in mouse (Vhlh) was generated to examine the pathophysiological role of the VHL gene function...
October 12, 2016: BMC Cancer
Yan-Su Chen, Fei Meng, Hai-Long Li, Qing-Hua Liu, Ping-Fu Hou, Jin Bai, Jun-Nian Zheng
Dicer, a key component of the microRNA processing machinery, has been reported to exert discrepant prognostic values and biological roles in different types of cancers. Here, we investigated the function and prognostic value of Dicer in clear cell renal cell carcinoma (ccRCC). Using the retrospective ccRCC patients' cohorts with tissue microarray (TMA), we demonstrated that Dicer expression was significantly down-regulated in ccRCC compared with renal non-tumor tissues, and negatively associated with pN status (P = 0...
October 8, 2016: Oncotarget
David M Gill, David D Stenehjem, Kinjal Parikh, Joseph Merriman, Arun Sendilnathan, Archana M Agarwal, Andrew W Hahn, Sumati Gupta, Srinivas Kiran Tantravahi, Wolfram E Samlowski, Neeraj Agarwal
Conditional survival (CS) is a clinically useful prediction measure which adjusts a patient's prognosis based on their duration of survival since initiation of therapy. CS has been described in numerous malignancies, and recently described in patients with metastatic renal cell carcinoma (mRCC) who received vascular endothelial growth factor tyrosine kinase inhibitor (VEGFTKI) therapy. However, CS has been not reported in the context of mRCC treated with high-dose interleukin-2 therapy (HDIL-2). A total of 176 patients with histologically confirmed metastatic clear cell RCC (mccRCC) treated with HDIL-2 at the University of Utah Huntsman Cancer Institute from 1988-2012 were evaluated...
2016: Ecancermedicalscience
Anastasia Asimakopoulou, Sabine Weiskirchen, Ralf Weiskirchen
Lipocalin 2 (LCN2) is a secreted protein that belongs to the Lipocalins, a group of transporters of small lipophilic molecules such as steroids, lipopolysaccharides, iron, and fatty acids in circulation. Two decades after its discovery and after a high variety of published findings, LCN2's altered expression has been assigned to critical roles in several pathological organ conditions, including liver injury and steatosis, renal damage, brain injury, cardiomyopathies, muscle-skeletal disorders, lung infection, and cancer in several organs...
2016: Frontiers in Physiology
Sumanta K Pal, Harry A Drabkin, James A Reeves, John D Hainsworth, Susan E Hazel, Dario A Paggiarino, Jon Wojciak, Gary Woodnutt, Rupal S Bhatt
BACKGROUND: Upregulation of sphingosine-1-phosphate (S1P) may mediate resistance to vascular endothelial growth factor (VEGF)-directed therapies and inhibit antitumor immunity. Antagonism of S1P in preclinical models appears to overcome this resistance. In this phase 2 study, the authors assessed the activity of sonepcizumab, a first-in-class inhibitor of S1P, in patients with metastatic renal cell carcinoma (mRCC) with a history of prior VEGF-directed therapy. METHODS: Patients were required to have clear cell mRCC and to have received treatment with at least 1 prior VEGF-directed agent...
October 11, 2016: Cancer
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