Science.gov

Sample records for renal cell populations

  1. Experimental depletion of different renal interstitial cell populations

    SciTech Connect

    Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

    1988-04-01

    To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells.

  2. Renal cell carcinoma in the pediatric population: Results from the California Cancer Registry.

    PubMed

    Silberstein, Jonathan; Grabowski, Julia; Saltzstein, Sidney L; Kane, Christopher J

    2009-02-01

    Renal cell carcinoma (RCC) is a rare disease in children and adolescents. This study aimed to review epidemiologic characteristics and survival for pediatric RCC patients using a large, population-based database. The California Cancer Registry (CCR) was reviewed from 1988 to 2004. All cases of RCC in patients younger than 21 years were identified and annual age-adjusted incidence rates were determined for the overall population and subdivided by ethnicity. Tumors were classified by stage and grade, and actuarial mortality rates were calculated. From 1988 to 2004, 43 cases of RCC were identified in patients younger than 21 years, accounting for 4.3% of all renal tumors in this age group. The overall annual age-adjusted incidence was 0.01/100,000 with the tumor more common in non-Hispanic blacks (0.03/100,000) compared to non-Hispanic whites (0.01/100,000), Hispanics (<0.01/100,000), and non-Hispanic Asians/Pacific Islanders (<0.01/100,000). The mean age at presentation was 15.4 years (SD 4.03, SE 0.615). RCC was identified more frequently in females (58.14%). At the time of presentation, 53.49% of tumors were localized, 20.93% were regionally advanced, and 25.58% were metastatic. The observed actuarial survival at 5 and 10 years was 61% (+/-15.7%). Pediatric RCC is an uncommon and aggressive tumor that occurs most frequently in children in the second decade of life, more often in females and blacks. The epidemiological characteristics of this tumor differ from adult RCC and Wilms tumor, suggesting its distinctive biology and potential need for alternative treatment strategies. (c) 2008 Wiley-Liss, Inc.

  3. Renal transplant recipient with advanced HIV infection: graft and peripheral cell population analysis

    PubMed Central

    Bostock, Ian C; Furuzawa-Carballeda, Janette; Gómez-Martín, Diana; Lima, Guadalupe; Martin-Onraët, Alexandra; Sierra, Juan; Uribe-Uribe, Norma O; Vilatobá, Mario; Contreras, Alan G; Gabilondo, Bernardo; Morales-Buenrostro, Luis E; Alberú, Josefina

    2013-01-01

    Key Clinical Message The scenario of a renal transplant recipient who is diagnosed with HIV infection in the late post transplant period is very uncommon. The viral infection effect on immunologic stability, regulatory cells, and allogeneic response during immune quiescence and graft acceptance provides a fertile ground in organ transplantation research and translational immunology. PMID:25356218

  4. Participation of different macrophage populations and myofibroblastic cells in chronically developed renal interstitial fibrosis after cisplatin-induced renal injury in rats.

    PubMed

    Yamate, J; Sato, K; Ide, M; Nakanishi, M; Kuwamura, M; Sakuma, S; Nakatsuji, S

    2002-05-01

    To shed some light on the mechanisms behind renal fibrogenesis, the present study immunohistochemically investigated the participation of different macrophage populations and myofibroblastic cells in rat renal interstitial fibrosis developed chronically after repeated injection of cisplatin (2 mg/kg body weight, once weekly for 7 weeks). During the 19-week recovery period after the final injection, fibrotic lesions progressively developed in the corticomedullary junction, with the greatest level at post-final injection (FPI) week 5, and then the lesions were gradually repaired by PFI week 19, indicative of a healing process. In conformity with the development of fibrotic lesions, the number of myofibroblastic cells reacting with an anti-alpha-smooth muscle actin antibody was increased, with a peak at PFI week 3, and collagens (types I, III, and IV), fibronection, and laminin were excessively accumulated in these areas. Interstitial cells forming the fibrotic lesions showed mitotic activity at the early stages, whereas they disappeared by apoptosis in the healing process. A large number of cells reacting with an antibody of ED1 (for exudate macrophages), ED2 (for resident macrophages), or OX6 (for major histocompatibility complex class II-presenting macrophages and interstitial dendritic cells) had already appeared at PF1 week 1, and then their numbers increased, with a peak at PFI weeks 7, 3, and 9 in ED1-, ED2-, and OX6-positive cells, respectively. Thereafter, the number of ED1- and ED2-positive cells decreased, whereas the number of OX6-positive cells persisted at a high level until PFI week 19. In the healing process, clusters of lymphocytes were present, the development of which might have been related to OX6-positive cells. The present study demonstrated that chronically developing rat renal interstitial fibrosis might be produced by the complicated mechanisms evoked by interactions between different macrophage populations and myofibroblastic cells, because

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:27891093

  7. Population based analysis of survival in patients with renal cell carcinoma and venous tumor thrombus.

    PubMed

    Whitson, Jared M; Reese, Adam C; Meng, Maxwell V

    2013-02-01

    To identify prognostic factors for renal cell carcinoma (RCC) with venous tumor thrombus (VTT) and determine the significance of thrombus level on survival. Patients within the Surveillance, Epidemiology, and End Results (SEER) database with RCC and VTT were identified and included if managed surgically. The Kaplan-Meier method and Cox regression analyses were performed to identify factors associated with disease-specific survival. A total of 1,875 patients met the inclusion criteria. One-year survival for patients undergoing surgery was 60% for patients with metastases and 90% for those without. Factors associated with worse survival included larger tumor size (HR 1.2, 95% CI 1.0-1.4), medullary, collecting duct, or sarcomatoid histology (HR 2.2, 95% CI 1.5-3.3), Fuhrman grade 3 (HR 2.2, 95% CI 1.5-3.3) or grade 4 (HR 2.9, 95% CI 1.8-4.5) tumors, positive lymph nodes (HR 1.5, 95% CI 1.0-2.0), and metastases (HR 3.5, 95% CI 2.6-4.8). Thrombus level above the diaphragm (T3c) was not significantly associated with worse survival (HR 1.4, 95% CI 0.8-2.5). In this large, population-based study of patients with RCC and VTT, we identify several disease-specific factors strongly associated with cancer-specific mortality. After controlling for adverse prognostic factors, thrombus level was not associated with worse outcome. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Chromophobe cell renal carcinoma.

    PubMed

    Megumi, Y; Nishimura, K

    1998-01-01

    Chromophobe cell renal carcinoma is a recently established subtype of renal cell carcinoma. Herein we report a case of chromophobe cell renal carcinoma in a 67-year-old male patient who occasionally underwent computed tomography. In a microscopic study with hematoxylin and eosin stain, clear eosinophilic cytoplasm, and a moderately atypical nucleus were observed. And it was stained positively by Hale's colloidal iron. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. From these results, this tumor was pathologically diagnosed as chromophobe cell renal carcinoma.

  9. One-Carbon Metabolism Pathway Gene Variants and Risk of Clear Cell Renal Cell Carcinoma in a Chinese Population

    PubMed Central

    Cai, Hongzhou; Li, Pu; Cao, Qiang; Shao, Pengfei; Qin, Chao; Yin, Changjun

    2013-01-01

    Background One-carbon metabolism is the basement of nucleotide synthesis and the methylation of DNA linked to cancer risk. Variations in one-carbon metabolism genes are reported to affect the risk of many cancers, including renal cancer, but little knowledge about this mechanism is known in Chinese population. Methods Each subject donated 5 mL venous blood after signing the agreement. The study was approved by the Institutional Review Board of the Nanjing Medical University, Nanjing, China. 18 SNPs in six one-carbon metabolism-related genes (CBS, MTHFR, MTR, MTRR, SHMT1, and TYMS) were genotyped in 859 clear cell renal cell carcinoma (ccRCC) patients and 1005 cancer-free controls by the Snapshot. Results Strong associations with ccRCC risk were observed for rs706209 (P = 0.006) in CBS and rs9332 (P = 0.027) in MTRR. Compared with those carrying none variant allele, individuals carrying one or more variant alleles in these two genes had a statistically significantly decreased risk of ccRCC [P = 0.001, adjusted odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.06–0.90]. In addition, patients carrying one or more variant alleles were more likely to develop localized stage disease (P = 0.002, adjusted OR = 1.37, 95%CI = 1.11–1.69) and well-differentiated ccRCC (P<0.001, adjusted OR = 1.42, 95%CI = 0.87–1.68). In the subgroup analysis, individuals carrying none variant allele in older group (P = 0.007, adjusted OR = 0.67, 95%CI = 0.49–0.91), male group (P = 0.007, adjusted OR = 0.71, 95%CI = 0.55–0.92), never smoking group (P = 0.002, adjusted OR = 0.68, 95%CI = 0.53–0.88) and never drinking group (P<0.001, adjusted OR = 0.68, 95%CI = 0.53–0.88) had an increased ccRCC risk. Conclusions Our results suggest that the polymorphisms of the one-carbon metabolism-related genes are associated with ccRCC risk in Chinese population. Future population-based prospective studies

  10. Age-dependent association between sex and renal cell carcinoma mortality: a population-based analysis.

    PubMed

    Qu, Yuanyuan; Chen, Haitao; Gu, Weijie; Gu, Chengyuan; Zhang, Hailiang; Xu, Jianfeng; Zhu, Yao; Ye, Dingwei

    2015-03-17

    Research on sex differences in renal cancer-specific mortality (RCSM), which considered the sex effect to be constant throughout life, has yielded conflicting results. This study hypothesized the sex effect may be modified by age, which is a proxy for hormonal status. Data from the Surveillance, Epidemiology and End Results database (1988-2010) were used to identify 114,539 patients with renal cell carcinoma (RCC). The study cohort was divided into three age groups using cutoffs of 42 and 58 years, which represent the premenopausal and postmenopausal periods. The cumulative incidence function and competing risks analyses were used to examine the effect of covariates on RCSM and other-cause mortality (OCM). In premenopausal period, male sex was a significant predictor of poor RCSM for both localized (adjusted subdistribution hazard ratio [aSHR] = 1.63, P = 0.002) and advanced (aSHR = 1.20, P = 0.041) disease. In postmenopausal period, the sex disparity diminished (aSHR = 1.05, P = 0.16) and reversed (aSHR = 0.95, P = 0.017) in localized and advanced disease, respectively. On the contrary, similar trend was not found for OCM across all age groups. Our results demonstrated the sex effect on RCSM was strongly modified by age. These findings may aid in clinical practice and need further evaluation of underlying biological mechanisms.

  11. Genetic variation in IGF1 predicts renal cell carcinoma susceptibility and prognosis in Chinese population

    PubMed Central

    Cao, Qiang; Liang, Chao; Xue, Jianxin; Li, Pu; Li, Jie; Wang, Meilin; Zhang, Zhengdong; Qin, Chao; Lu, Qiang; Hua, Lixin; Shao, Pengfei; Wang, Zengjun

    2016-01-01

    Insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3) play an important role in the development and progression of renal cell carcinoma (RCC). We evaluated the association of functional polymorphisms in IGF1 and IGFBP3 with susceptibility and prognosis of RCC. We genotyped nine potentially functional polymorphisms in IGF1 and IGFBP3 and assessed their association with risk of RCC in a two-stage case-control study compromising 1027 cases and 1094 controls, and with prognosis in a cohort of 311 patients. We found rs5742714 in the 3′-UTR of IGF1 was significantly associated with risk and prognosis of RCC. In the combined set, the rs5742714 GC/CC genotypes were significantly associated with decreased risk of RCC compared with the GG genotype (OR = 0.82; 95% CI = 0.68–0.98, P = 0.002). Furthermore, patients with the rs5742714 GC/CC genotypes showed improved survival than those with the GG genotype (Log-rank P = 0.025, HR = 0.36, 95% CI = 0.14–0.93). Besides, the rs5742714 GC/CC genotypes were associated with significantly decreased expression of IGF1 mRNA and lower IGF1 serum levels. Moreover, the luciferase reporter assays revealed the potential effect of rs5742714 genotype on the binding of microRNAs to IGF1. Our findings suggest that the IGF1 polymorphism rs5742714 may be a genetic predictor of susceptibility and prognosis of RCC. PMID:27976731

  12. [Imaging renal cell carcinoma].

    PubMed

    Bazan, F; Busto, M

    2014-01-01

    Renal cell carcinoma is the eighth most common malignancy in adults and the most common malignancy in the kidney. It is thus a very common disease for radiologists. This review aims to provide a general overview of the imaging techniques used to diagnose, characterize, and help plan the treatment of renal cell carcinoma as well as to review basic aspects related to staging, imaging-guided percutaneous treatment, and follow-up in the most common clinical scenarios. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  13. Human renal tubular cells contain CD24/CD133 progenitor cell populations: Implications for tubular regeneration after toxicant induced damage using cadmium as a model.

    PubMed

    Shrestha, Swojani; Somji, Seema; Sens, Donald A; Slusser-Nore, Andrea; Patel, Divyen H; Savage, Evan; Garrett, Scott H

    2017-09-15

    The proximal tubules of the kidney are target sites of injury by various toxicants. Cadmium (Cd(+2)), an environmental nephrotoxicant can cause adverse effects and overt renal damage. To decipher the mechanisms involved in nephrotoxicity, an in vitro model system is required. Mortal cultures of human proximal tubule (HPT) cells have served, as models but are difficult to acquire and do not lend themselves to stable transfection. The immortalized human proximal tubule cell line HK-2, has served as a model but it lacks vectorial active transport and shows signs of lost epithelial features. Recently a new proximal tubule cell line was developed, the RPTEC/TERT1, and the goal of this study was to determine if this cell line could serve as a model to study nephrotoxicity. Global gene expression analysis of this cell line in comparison to the HK-2 and HPT cells showed that the RPTEC/TERT1 cells had gene expression patterns similar to HPT cells when compared to the HK-2 cells. The HPT and the RPTEC/TERT1 cell line had an increased population of stem/progenitor cells co-expressing CD24 and CD133 when compared to the HK-2 cells. The level of expression of cadherins, claudins and occludin molecules was also similar between the RPTEC/TERT1 and the HPT cells. Acute exposure to Cd(+2) resulted in necrosis of the RPTEC/TERT1 cells when compared to the HK-2 cells which died by apoptosis. Thus, the RPTEC/TERT1 cells are similar to HPT cells and can serve as a good model system to study mechanisms involved in toxicant induced renal damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Renal Medullary Interstitial Cells

    NASA Astrophysics Data System (ADS)

    Rao, Reena; Hao, Chuan-Ming; Breyer, Matthew D.

    2007-04-01

    Renal medullary interstitial cells (RMICs) are specialized fibroblast-like cells that reside in the renal medulla among the vasa recta, the thin limbs of Henle's loop, and medullary collecting ducts. These cells are characterized by abundant lipid droplets in the cytoplasm. The lipid droplets are composed of triglycerides, cholesterol esters and free long-chain fatty acids, including arachidonic acid. RMICs are also a major site of cyclooxygenase2 (COX-2) expression, and thus a major site of COX-2 derived prostanoid biosynthesis. RMICs are also a potential target of hormones such as angiotensin II and endothelin. The RMIC COX-2 expression and the abundance of lipid droplets change with salt and water intake. These properties of RMICs are consistent with an important role of these cells in modulating physiologic and pathologic processes of the kidney.

  15. Overall survival in renal cell carcinoma after introduction of targeted therapies: a Norwegian population-based study

    PubMed Central

    Beisland, Christian; Johannesen, Tom B; Klepp, Olbjorn; Axcrona, Ulrika; Torgersen, Knut Martin; Kowalski, Jan; Solli, Oddvar; Sandin, Rickard; Oldenburg, Jan

    2017-01-01

    Background This population-wide retrospective, non-interventional registry study assessed changes in overall survival (OS) and factors influencing OS in Norwegian patients with renal cell carcinoma (RCC). Methods Two population-wide health registries were used to identify all RCC patients with (mRCC) or without metastases diagnosed before (2002–2005) and after (2006–2008 and 2009–2011) introduction of targeted therapies. Median OS was estimated using Kaplan–Meier method. Cox proportional hazards regression modeling was used to identify prognostic factors. Results Overall, 5,463 patients were diagnosed with RCC during 2002–2005 (n=1,898), 2006–2008 (n=1,631), and 2009–2011 (n=1,934); of these, 1,678 (31%) had mRCC. Patients diagnosed in 2009–2011 and 2006–2008 had significant (P<0.001) improvements in OS versus those diagnosed in 2002–2005: median OS, not reached and not reached versus 82.0 months in RCC; 14.0 and 12.0 months versus 9.0 months in mRCC. Similarly, OS improvements were seen in the primary and elderly (≥75 years) mRCC populations. Median OS was comparable (12 months) between clear cell and papillary mRCC, but it was longer (24.0 months) for chromophobe mRCC. Multivariate regression analyses showed that younger age, previous nephrectomy, and 1 or more prescriptions of targeted therapy were significantly associated with longer OS in mRCC patients. Conclusion OS increased in RCC and mRCC patients in Norway between 2002 and 2011 following introduction of targeted therapies. PMID:28144152

  16. Cytoreductive partial nephrectomy does not undermine cancer control in metastatic renal cell carcinoma: a population-based study.

    PubMed

    Capitanio, Umberto; Zini, Laurent; Perrotte, Paul; Shariat, Shahrokh F; Jeldres, Claudio; Arjane, Philippe; Pharand, Daniel; Widmer, Hugues; Péloquin, François; Montorsi, Francesco; Patard, Jean-Jacques; Karakiewicz, Pierre I

    2008-11-01

    We examined the population-based rates of cancer-specific survival in patients with metastatic renal cell carcinoma (MRCC) treated with either partial (PN) or radical cytoreductive nephrectomy (RN). Patients diagnosed with MRCC and treated with either PN or RN were identified within nine SEER cancer registries. Matched and unmatched Kaplan-Meier survival analyses, as well as multivariable Cox regression models compared the effect of RN (n = 1997, 97.8%) vs. PN (n = 46, 2.2%) on cancer-specific survival (CSS). Covariates consisted of age, gender, community type (rural vs urban), race, Surveillance, Epidemiology, and End Results (SEER) registry, tumor size and year of diagnosis. In multivariable unmatched Cox regression analyses, no statistically significantly difference was found in CSS between the two groups (hazard ratio [HR] 1.40, P = .16). Similarly, no difference in CSS was found in the matched analyses (HR 1.35, log rank P = .34). Cytoreductive PN does not appear to undermine survival in patients with MRCC.

  17. Subfractionation of Differentiating Human Embryonic Stem Cell Populations Allows the Isolation of a Mesodermal Population Enriched for Intermediate Mesoderm and Putative Renal Progenitors

    PubMed Central

    Lin, S. Adelia; Kolle, Gabriel; Grimmond, Sean M.; Zhou, Qi; Doust, Elizabeth; Little, Melissa H.; Aronow, Bruce; Ricardo, Sharon D.; Pera, Martin F.; Bertram, John F.

    2010-01-01

    Human embryonic stem (ES) cells are pluripotent and are believed to be able to generate all cell types in the body. As such, they have potential applications in regenerative therapy for kidney disease. However, before this can be achieved, a protocol to differentiate human ES cells to mesodermal renal progenitor lineages is required. Reduction of serum concentration and feeder layer density reduction cultures were used to differentiate human ES cells for 14 days. Differentiated ES cells were then fractionated by flow cytometry based on expression of the markers CD24, podocalyxin, and GCTM2 to isolate putative renal cells. These cells up-regulated the expression of the renal transcription factors PAX2, LHX1, and WT1 when compared with unfractionated human ES cells. Immunohistochemical assays confirmed that a subset of cells within this fraction co-expressed nuclear WT1 and PAX2 proteins. Transcriptome profiling also showed that the most differentially up-regulated genes in this fraction preferentially associated with kidney development in comparison with any other lineage. When compared with a transcriptome profile database of urogenital development (GUDMAP), the top 200 differentially up-regulated genes in this fraction strongly clustered into a group of genes associated with the metanephric mesenchyme at E11.5 and the corticonephrogenic interstitium at E15.5 of murine kidney development. Hence, this approach confirms an ability to direct human ES cells toward a renal progenitor state. PMID:20143954

  18. Measuring quality care in localized renal cell cancer: use of appropriate preoperative investigations in a population-based cohort.

    PubMed

    Moideen, N; Marzouk, K H; Matheson, K J; Wood, L A

    2017-04-01

    Obtaining appropriate preoperative risk-specific staging investigations for localized renal cell carcinoma (rcc) is a recognized quality indicator. The goal of the present work was to determine the use and appropriateness of preoperative investigations in patients undergoing curative surgery for rcc. This population-based retrospective study of patients having surgery for localized rcc recorded the use of preoperative imaging and laboratory investigations within 6 months of surgery. "Appropriate" stage-specific investigations were determined using recognized published guidelines. The study cohort consisted of 544 patients with 72.8% being stage i, 18.4% being stage ii, and 8.8% being stage iii by clinical TNM (2002) criteria. In 61.6%, chest imaging was obtained by chest radiography or computed tomography (ct) within 3 months preoperatively; in 75.6%, such imaging was obtained within 6 months. Abdominal ct imaging was obtained in 97.1% of patients before surgery, with 77.5% of patients receiving such imaging within 3 months of surgery. Complete blood count, electrolytes, and creatinine were measured in 99.1% of patients, but those tests plus other recommended blood tests including calcium, alkaline phosphatase, and liver function were measured in only 17.7%. In this study, most patients received appropriate abdominal imaging, but chest imaging was underutilized in the overall cohort. Despite being recommended, blood tests such as liver function, alkaline phosphatase, and calcium were completed in fewer than 2 of 10 patients. This analysis provides the groundwork for quality improvement initiatives directed to the use of preoperative investigations in localized rcc.

  19. Renal cell carcinoma.

    PubMed

    Hsieh, James J; Purdue, Mark P; Signoretti, Sabina; Swanton, Charles; Albiges, Laurence; Schmidinger, Manuela; Heng, Daniel Y; Larkin, James; Ficarra, Vincenzo

    2017-03-09

    Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy.

  20. Contemporary Renal Cell Cancer Epidemiology

    PubMed Central

    Chow, Wong-Ho; Devesa, Susan S.

    2010-01-01

    We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers. PMID:18836333

  1. Isolation, characterization, and expansion methods for defined primary renal cell populations from rodent, canine, and human normal and diseased kidneys.

    PubMed

    Presnell, Sharon C; Bruce, Andrew T; Wallace, Shay M; Choudhury, Sumana; Genheimer, Christopher W; Cox, Bryan; Guthrie, Kelly; Werdin, Eric S; Tatsumi-Ficht, Patricia; Ilagan, Roger M; Kelley, Russell W; Rivera, Elias A; Ludlow, John W; Wagner, Belinda J; Jayo, Manuel J; Bertram, Timothy A

    2011-03-01

    Chronic kidney disease (CKD) is a global health problem; the growing gap between the number of patients awaiting transplant and organs actually transplanted highlights the need for new treatments to restore renal function. Regenerative medicine is a promising approach from which treatments for organ-level disorders (e.g., neurogenic bladder) have emerged and translated to clinics. Regenerative templates, composed of biodegradable material and autologous cells, isolated and expanded ex vivo, stimulate native-like organ tissue regeneration after implantation. A critical step for extending this strategy from bladder to kidney is the ability to isolate, characterize, and expand functional renal cells with therapeutic potential from diseased tissue. In this study, we developed methods that yield distinct subpopulations of primary kidney cells that are compatible with process development and scale-up. These methods were translated to rodent, large mammal, and human kidneys, and then to rodent and human tissues with advanced CKD. Comparative in vitro studies demonstrated that phenotype and key functional attributes were retained consistently in ex vivo cultures regardless of species or disease state, suggesting that autologous sourcing of cells that contribute to in situ kidney regeneration after injury is feasible, even with biopsies from patients with advanced CKD.

  2. Renal tubule cell repair following acute renal injury.

    PubMed

    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.

  3. Renal stem cells: fact or science fiction?

    PubMed

    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.

  4. Tubulocystic Renal Cell Carcinoma: A Rare Renal Tumor

    PubMed Central

    Bindroo, Sandiya; Varshney, Neha; Mittal, Vijay

    2014-01-01

    Tubulocystic renal cell carcinoma of the kidney is a rare entity with less than one hundred cases reported so far. It was previously considered to have some similarities to various other renal cancers although this tumor has distinct macroscopic, microscopic and immuno-histochemical features. It is now a well-established entity in renal neoplastic pathology and has been recognized as a distinct entity in the 2012 Vancouver classification of renal tumors. This review aims to give an overview of tubulocystic renal cell carcinoma after extensive literature search using PubMed and CrossRef.

  5. PKCε inhibits isolation and stemness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P.

    PubMed

    Huang, Bin; Fu, Shun Jun; Fan, Wen Zhe; Wang, Zhong Hua; Chen, Ze Bin; Guo, Sheng Jie; Chen, Jun Xing; Qiu, Shao Peng

    2016-06-28

    Protein kinase C epsilon (PKCε), a member of the novel PKC family, is known to be a transforming oncogene and tumor biomarker for many human solid cancers including renal cell carcinoma (RCC). We isolated side population (SP) cells from the RCC 769P cell line, and proved that those cells possess cancer stem cell (CSC) characteristics. In this study, to identify the function of PKCε in cancer stemness of 769P SP cells, we reduced the expression of PKCε in those cells, following the results demonstrated that PKCε depletion had a negative correlation with the existence of SP cells in 769P cell line. Down-regulation of PKCε also suppresses the CSC potential of sorted 769P SP cells in several ways: proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. Our study also reveals that PKCε is associated with ABCB1 and this association probably contributed to the SP cells isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly regulated by PKCε. Additionally, after the depletion of PKCε, the phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP cells, whereas PKCε overexpression could promote the phosphorylation of AKT, STAT3 and ERK in 769P Non-SP cells. Overall, PKCε down-regulation suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK pathways that are dependent on the phosphorylation effects. Thus, PKCε may work as an important mediator in cancer stem cell pathogenesis of renal cell cancer.

  6. Sorafenib in renal cell carcinoma.

    PubMed

    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.

  7. IL-16 rs4778889 polymorphism contribution to the development of renal cell cancer in a Chinese population.

    PubMed

    Yang, S X; Chen, F; Zhang, J W; Sun, Z Q; Chen, B P

    2016-06-10

    IL-16 plays an important role in affect the secretion of tumor-related inflammatory cytokines. We aimed to assess the role of interleukin-16 (IL-16) rs4778889 T/C and rs11556218 T/G polymorphisms in the occurrence of renal cell cancer (RCC). This study is composed of 274 RCC patients and 274 control subjects. Genotyping of polymorphisms was performed using polymerase chain reaction combined with restriction fragment length polymorphism analysis. All statistical analysis was carried out by the SPSS statistical software package, version 16.0 (SPSS Inc., Chicago, IL, USA). Using conditional logistic regression analysis, the TC and CC genotypes of rs4778889 exhibited a higher risk of RCC, with adjusted ORs (and 95%CIs) of 1.79 (1.23-2.62) and 2.67 (1.29-5.69), respectively. Moreover, under dominant and recessive models, individuals carried the rs4778889 polymorphism was exhibited elevated RCC risk, with adjusted ORs (and 95%CI) of 1.93 (1.35-2.76) and 2.11 (1.05-4.45), respectively. No significant differences were observed in rs11556218 genotype frequencies between the study groups. In conclusion, the results of our study reveal an association between the IL-16 rs4778889 polymorphism and heightened risk of RCC.

  8. The impact of tumour size on the probability of synchronous metastasis and survival in renal cell carcinoma patients: a population-based study.

    PubMed

    Ingimarsson, Johann P; Sigurdsson, Martin I; Hardarson, Sverrir; Petursdottir, Vigdis; Jonsson, Eirikur; Einarsson, Gudmundur V; Gudbjartsson, Tomas

    2014-08-31

    The observed low metastatic potential and favorable survival of small incidentally detected renal cell carcinomas (RCCs) have been a part of the rationale for recommending partial nephrectomy as a first treatment option and active surveillance in selected patients. We examined the relationship between tumor size and the odds of synchronous metastases (SMs) (primary outcome) and disease specific survival (secondary outcome) in a nationwide RCC registry. Retrospective study of the 794 RCC patients diagnosed in Iceland between 1971 and 2005. Histological material and TNM staging were reviewed centrally. The presence of SM and survival were recorded. Cubic spline analysis was used to assess relationship between tumor size and probability of SM. Univariate and multivariate statistics were used to estimate prognostic factors for SM and survival. The probability of SM increased in a non-linear fashion with increasing tumor size (11, 25, 35, and 50%) for patients with tumors of ≤4, 4.1-7.0, 7.1-10.0, and >10 cm, respectively. On multivariate analysis, tumor size was an independent prognostic factor for disease-specific survival (HR = 1.05, 95% CI 1.02-1.09, p < 0.001), but not for SM. Tumor size affected the probability of disease-specific mortality but not SM, after correcting for TNM staging in multivariate analysis. This confirms the prognostic ability of the 2010 TNM staging system for renal cell cancer in the Icelandic population.

  9. Drugs Approved for Kidney (Renal Cell) Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs ... that are not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) ...

  10. Retrospective claims analysis of best supportive care costs and survival in a US metastatic renal cell population.

    PubMed

    Henk, Henry J; Chen, Connie; Benedict, Agnes; Sullivan, Jane; Teitelbaum, April

    2013-01-01

    Survival and best supportive care (BSC) costs for patients with metastatic renal cell carcinoma (mRCC), after stopping therapy, are poorly characterized yet an important aspect of patient care. This study examined survival and costs associated with BSC after one or two lines of therapy (LOTs) for mRCC. A retrospective cohort analysis used claims data from commercially insured or Medicare Advantage Prescription Drug (MAPD) plan enrollees of a large United States health plan with an index RCC diagnosis (ICD-9-CM 189.0) between January 1, 2007 and June 30, 2010; initiating any of the following therapies 30 days pre-index date through disenrollment from plan: sunitinib, temsirolimus, sorafenib, bevacizumab, everolimus, pazopanib, cytokines. LOT was identified using prescription fill and administration dates. Health care costs represent health plan- plus patient-paid amounts. The cohort (n = 274) was 73% male, with a mean age of 63.3 years (SD 11.1), with 80% commercially insured (20% MAPD), and 68% starting BSC following one LOT. Mean BSC duration was longer following one than two LOTs (223 [SD 260], 176 [SD 163] days). Median survival from the start of BSC was similar following one and two LOTs (126 and 118 days). Total BSC costs following one and two LOTs averaged US$50,188 (SD $96,984) and $37,295 (SD $51,102). Monthly costs for BSC following one and two LOTs ($10,151 and $10,566) were not substantially lower than costs while on treatment ($14,621 and $16,957). Inpatient hospital costs represented 47% and 49% following one and two LOTs, with ambulatory costs of approximately 36% following each LOT. Our study found similar survival and monthly costs for BSC following either one or two LOTs, with almost half of the cost reflecting inpatient care. Compared to costs on treatment ($14,621 to $16,957), BSC costs can be considerable ($10,151 to $10,566).

  11. Cultured Human Renal Cortical Cells

    NASA Technical Reports Server (NTRS)

    1998-01-01

    During the STS-90 shuttle flight in April 1998, cultured renal cortical cells revealed new information about genes. Timothy Hammond, an investigator in NASA's microgravity biotechnology program was interested in culturing kidney tissue to study the expression of proteins useful in the treatment of kidney diseases. Protein expression is linked to the level of differentiation of the kidney cells, and Hammond had difficulty maintaining differentiated cells in vitro. Intrigued by the improvement in cell differentiation that he observed in rat renal cells cultured in NASA's rotating wall vessel (a bioreactor that simulates some aspects of microgravity) and during an experiment performed on the Russian Space Station Mir, Hammond decided to sleuth out which genes were responsible for controlling differentiation of kidney cells. To do this, he compared the gene activity of human renal cells in a variety of gravitational environments, including the microgravity of the space shuttle and the high-gravity environment of a centrifuge. Hammond found that 1,632 genes out of 10,000 analyzed changed their activity level in microgravity, more than in any of the other environments. These results have important implications for kidney research as well as for understanding the basic mechanism for controlling cell differentiation.

  12. Cultured Human Renal Cortical Cells

    NASA Technical Reports Server (NTRS)

    1998-01-01

    During the STS-90 shuttle flight in April 1998, cultured renal cortical cells revealed new information about genes. Timothy Hammond, an investigator in NASA's microgravity biotechnology program was interested in culturing kidney tissue to study the expression of proteins useful in the treatment of kidney diseases. Protein expression is linked to the level of differentiation of the kidney cells, and Hammond had difficulty maintaining differentiated cells in vitro. Intrigued by the improvement in cell differentiation that he observed in rat renal cells cultured in NASA's rotating wall vessel (a bioreactor that simulates some aspects of microgravity) and during an experiment performed on the Russian Space Station Mir, Hammond decided to sleuth out which genes were responsible for controlling differentiation of kidney cells. To do this, he compared the gene activity of human renal cells in a variety of gravitational environments, including the microgravity of the space shuttle and the high-gravity environment of a centrifuge. Hammond found that 1,632 genes out of 10,000 analyzed changed their activity level in microgravity, more than in any of the other environments. These results have important implications for kidney research as well as for understanding the basic mechanism for controlling cell differentiation.

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

    PubMed

    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

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

    PubMed Central

    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

  15. Retrospective claims analysis of best supportive care costs and survival in a US metastatic renal cell population

    PubMed Central

    Henk, Henry J; Chen, Connie; Benedict, Agnes; Sullivan, Jane; Teitelbaum, April

    2013-01-01

    Introduction Survival and best supportive care (BSC) costs for patients with metastatic renal cell carcinoma (mRCC), after stopping therapy, are poorly characterized yet an important aspect of patient care. This study examined survival and costs associated with BSC after one or two lines of therapy (LOTs) for mRCC. Methods A retrospective cohort analysis used claims data from commercially insured or Medicare Advantage Prescription Drug (MAPD) plan enrollees of a large United States health plan with an index RCC diagnosis (ICD-9-CM 189.0) between January 1, 2007 and June 30, 2010; initiating any of the following therapies 30 days pre-index date through disenrollment from plan: sunitinib, temsirolimus, sorafenib, bevacizumab, everolimus, pazopanib, cytokines. LOT was identified using prescription fill and administration dates. Health care costs represent health plan- plus patient-paid amounts. Results The cohort (n = 274) was 73% male, with a mean age of 63.3 years (SD 11.1), with 80% commercially insured (20% MAPD), and 68% starting BSC following one LOT. Mean BSC duration was longer following one than two LOTs (223 [SD 260], 176 [SD 163] days). Median survival from the start of BSC was similar following one and two LOTs (126 and 118 days). Total BSC costs following one and two LOTs averaged US$50,188 (SD $96,984) and $37,295 (SD $51,102). Monthly costs for BSC following one and two LOTs ($10,151 and $10,566) were not substantially lower than costs while on treatment ($14,621 and $16,957). Inpatient hospital costs represented 47% and 49% following one and two LOTs, with ambulatory costs of approximately 36% following each LOT. Conclusion Our study found similar survival and monthly costs for BSC following either one or two LOTs, with almost half of the cost reflecting inpatient care. Compared to costs on treatment ($14,621 to $16,957), BSC costs can be considerable ($10,151 to $10,566). PMID:23874112

  16. Paraneoplastic Cough and Renal Cell Carcinoma

    PubMed Central

    Sullivan, Stephen

    2016-01-01

    A case of patient with intractable cough due to renal cell carcinoma is reported. The discussion reviews the literature regarding this unusual paraneoplastic manifestation of renal malignancy. PMID:27445553

  17. CD133+ Renal Progenitor Cells Contribute to Tumor Angiogenesis

    PubMed Central

    Bruno, Stefania; Bussolati, Benedetta; Grange, Cristina; Collino, Federica; Efrem Graziano, Manuela; Ferrando, Ugo; Camussi, Giovanni

    2006-01-01

    In the present study, we tested the hypothesis that resident progenitor cells may contribute to tumor vascularization and growth. CD133+ cells were isolated from 30 human renal carcinomas and characterized as renal resident progenitor cells on the basis of the expression of renal embryonic and mesenchymal stem cell markers. CD133+ progenitors differentiated into endothelial and epithelial cells as the normal CD133+ counterpart present in renal tissue. In the presence of tumor-derived growth factors, these cells were committed to differentiate into endothelial cells able to form vessels in vivo in SCID mice. Undifferentiated CD133+ progenitors were unable to form tumors when transplanted alone in SCID mice. When co-transplanted with renal carcinoma cells, CD133+ progenitors significantly enhanced tumor development and growth. This effect was not attributable to the tumorigenic nature of CD133+ progenitor cells because the same results were obtained with CD133+ cells from normal kidney. CD133+ progenitors contributed to tumor vascularization as the majority of neoformed vessels present within the transplanted tumors were of human origin and derived from the co-transplanted CD133+ progenitors. In conclusion, these results indicate the presence of a renal progenitor cell population in renal carcinomas that may differentiate in endothelial cells and favor vascularization and tumor growth. PMID:17148683

  18. Tumour characteristics and surgical treatment of renal cell carcinoma in Sweden 2005-2010: a population-based study from the national Swedish kidney cancer register.

    PubMed

    Thorstenson, Andreas; Bergman, Martin; Scherman-Plogell, Ann-Helén; Hosseinnia, Soheila; Ljungberg, Börje; Adolfsson, Jan; Lundstam, Sven

    2014-06-01

    Tumour characteristics, preoperative work-up and surgical treatment in patients diagnosed with renal cell carcinoma (RCC) between 2005 and 2010, and changes over time were studied in a national population-based cohort. The National Swedish Kidney Cancer Register (NSKCR) contains information on histopathology, Fuhrman grade and clinical stage at presentation, and on the preoperative work-up and surgical treatment of patients with RCC. Between 2005 and 2010, 5553 RCC patients were registered in the NSKCR, 99% of those registered in the National Cancer Registry. During the study period the mean tumour size decreased from 70 to 64 mm (p = 0.024) and the frequency of metastatic RCC decreased from 22% to 15% (p < 0.001). The use of preoperative chest computed tomography increased from 59% to 84%. In total, 4229 (76%) patients were treated with curative intent, 3453 (82%) underwent radical nephrectomy, 606 (14%) partial nephrectomy (PN) and 170 (4%) cryotherapy or radiofrequency ablation. In tumours up to 4 cm, PN was performed in 33% of the surgically treated patients. PN irrespective of size increased from 8% to 20% and laparoscopic nephrectomy increased from 6% to 17% during the period. In patients with metastatic RCC, 55% underwent cytoreductive nephrectomy. The NSKCR explores population-based data on the clinical handling of patients with RCC. This study, between 2005 and 2010, shows significant decrease in tumour size and metastatic RCC at presentation, a more complete preoperative work-up, and significantly increased use of PN and laparoscopic nephrectomy in Sweden.

  19. A Genetic Variant in pre-miR-27a Is Associated with a Reduced Renal Cell Cancer Risk in a Chinese Population

    PubMed Central

    Zhong, Dongyan; Chu, Haiyan; Yan, Fu; Lv, Qiang; Qin, Chao; Wang, Wei; Wang, Meilin; Tong, Na; Zhang, Zhengdong; Yin, Changjun

    2012-01-01

    Background MicroRNAs (miRNAs) are a class of small non-coding RNAs to regulate cell differentiation, proliferation, development, and apoptosis. The single nucleotide polymorphism (SNP) rs895819 is located at the terminal loop of pre-miR-27a. Here, we aimed to investigate whether SNP rs895819 was associated with the development of renal cell cancer (RCC) in a Chinese population. Methods In this case-control study, we recruited 594 RCC patients and 600 cancer-free controls with frequency matched by age and sex. We genotyped this polymorphism using the TaqMan assay and assessed the effect of this polymorphism on RCC survival. Logistic regression model was used to assess the genetic effects on the development of RCC and interactions between rs895819 polymorphism and risk factors. Results Compared with AA homozygote, individuals carrying AG/GG genotypes had a statistically significant reduced susceptibility to RCC (adjusted OR = 0.71, 95% CI = 0.56–0.90). Furthermore, AG/GG genotypes were associated with reduced RCC susceptibility in localized clinical stage (adjusted OR = 0.71, 95% CI = 0.55–0.91), and similar effects were observed in well differentiated and poorly differentiated RCC (adjusted OR = 0.71, 95% CI = 0.55–0.93 for well differentiated, adjusted OR = 0.51, 95% CI = 0.28–0.93 for poorly differentiated). We also observed that rs895819 had multiplicative interactions with age and hypertension. However, the polymorphism did not influence the survival of RCC. Conclusion Our results suggest that the pre-miR-27a rs895819 polymorphism can predict RCC risk in a Chinese population. Larger population-based prospective studies should be used to validate our findings. PMID:23118855

  20. Biomarkers of renal cell carcinoma.

    PubMed

    Ngo, Tin C; Wood, Christopher G; Karam, Jose A

    2014-04-01

    The incidence of renal cell carcinoma (RCC) has increased steadily in past few decades and is partially attributable to the increased utilization of cross-sectional imaging. Many of these carcinomas are small incidental discoveries, although a subset leads to locally advanced or distant disease. Although its molecular pathophysiology is not completely understood, knowledge of hereditary RCCs has shed light on some of the pathways involved. More recently, the rapid advances in genomics, proteomics, and metabolomics have allowed for a deeper and more nuanced understanding of the genetic aberrations that lead up to and result from the transformation of a renal tubular epithelial cell into a carcinoma. These discoveries have allowed for the development of novel therapeutics that target these pathways. They have also led to the development of diagnostic, prognostic, and predictive biomarkers that could radically change the way RCC is diagnosed and treated. Although some of the current investigations are nascent and it remains to be seen which biomarkers will become clinically available, many candidate biomarkers show promise and require external validation. Ultimately, biomarkers may allow for cost-effective screening of high-risk patients, the identification of aggressive cancers among small renal masses, the identification of high-risk patients, the detection of recurrences postoperatively with minimal imaging, and the ability to choose appropriate targeted therapies for patients with metastatic disease.

  1. Development of bioartificial renal tubule devices with lifespan-extended human renal proximal tubular epithelial cells.

    PubMed

    Sanechika, Noriyuki; Sawada, Kaichiro; Usui, Yukio; Hanai, Kazuya; Kakuta, Takatoshi; Suzuki, Hajime; Kanai, Genta; Fujimura, Satoshi; Yokoyama, Tun Aung; Fukagawa, Masafumi; Terachi, Toshiro; Saito, Akira

    2011-09-01

    The bioartificial renal tubule device is a cell therapy system for renal failure. The major obstacle in the development of the bioartificial renal tubule device is the obtainment of a large number of viable renal tubule cells to seed on the inner surface of hollow fibers. Although our previous studies had used a transformed cell line, they may be dangerous for clinical uses. Therefore, different approaches to amplify renal proximal tubular epithelial cells (RPTEC) in culture without oncogenes, vectors and carcinogens have been required. The limitation of the replicative lifespan of human RPTEC, which is ∼12 population doublings (PDs), was extended by invalidating messenger RNA of cell cycle-related genes with antisense oligonucleotide or small interfering RNA (siRNA). Periodic transfection of siRNA to a tumor suppressor p53 or a cyclin-dependent kinase inhibitor p16(INK4a) extended the lifespan by 33 and 63 PDs, respectively, in 3 months of culture. The siRNA-mediated lifespan extension was controllable because cell division ceased within 2 weeks after the transfection was discontinued. Expressions of γ-glutamyltransferase 1 and glucose transporter 1 were recovered in siRNA-transfected RPTEC cultured on porous membranes. Bioartificial renal tubule devices (0.8 m(2)) constructed with these cells showed reabsorption of water (122.3 ± 4.2 mL/30 min), sodium (18.1 ± 0.7 mEq/30 min) and glucose (121.7 ± 4.4 mg/30 min) after 1 week of circulation. Furthermore, β2-microglobulin and pentosidine were metabolized by RPTEC in mini-devices (65 cm(2)) within 48 h of circulation. These approaches enabled us to yield a high enough number of RPTEC for construction of bioartificial renal tubule devices repeatedly. Lifespan-extended RPTEC could recover their specific characteristics by culturing on porous membranes, and bioartificial renal tubule devices constructed with these cells showed good performances of reabsorption and metabolism. A large number of human renal tubular

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

    PubMed

    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.

  3. Fever of unknown origin (FUO) and a renal mass: renal cell carcinoma, renal tuberculosis, renal malakoplakia, or xanthogranulomatous pyelonephritis?

    PubMed

    Chandrankunnel, Joseph; Cunha, Burke A; Petelin, Andrew; Katz, Douglas

    2012-01-01

    Often patients with fevers of unknown origin (FUOs) present with loss of appetite, weight loss, and night sweats, without localizing signs. Some are found to have a renal mass during diagnostic evaluation. In patients with FUOs and a renal mass, the differential diagnosis includes renal tuberculosis, renal cell carcinoma (hypernephroma), renal malakoplakia, and xanthogranulomatous pyelonephritis. A 68-year-old woman presented with an FUO during her diagnostic workup. She manifested an irregularly enlarged kidney on abdominal computed tomography (CT) scan, as well as a highly elevated erythrocyte sedimentation rate of more than 100 mm/hour, an elevated serum ferritin level, and chronic thrombocytosis, which favored a diagnosis of renal cell carcinoma. Renal malakoplakia and renal tuberculosis comprised further differential diagnostic considerations. Microscopic hematuria may be present with any of the disorders in the differential diagnosis, but was absent in this case. An abdominal CT scan was suggestive of xanthogranulomatous pyelonephritis. Because of concerns regarding renal cell carcinoma, the patient received a nephrectomy. The pathologic diagnosis was of xanthogranulomatous pyelonephritis, without renal cell carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Renal Clear Cell Carcinoma and Tonsil Metastasis

    PubMed Central

    Marcotullio, Dario; Iannella, Giannicola; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site. PMID:24455373

  5. Renal clear cell carcinoma and tonsil metastasis.

    PubMed

    Marcotullio, Dario; Iannella, Giannicola; Macri, Gian Franco; Marinelli, Caterina; Zelli, Melissa; Magliulo, Giuseppe

    2013-01-01

    Renal cell carcinoma is the most common renal tumor in adults. Clear cell carcinoma represents 85% of all histological subtypes. In February 2012 a 72-year-old woman came to our department due to the appearance of massive hemoptysis and pharyngodinia. Previously, this patient was diagnosed with a renal cell carcinoma treated with left nephrectomy. We observed an exophytic, grayish, and ulcerated mass in the left tonsillar lodge and decided to subject the patient to an immediate tonsillectomy. Postoperative histology showed nests of cells with highly hyperchromatic nuclei and clear cytoplasm. These features enabled us to make the diagnosis of renal clear cell carcinoma metastasis. Only few authors described metastasis of renal cell carcinoma in this specific site.

  6. Sickle cell disease: renal manifestations and mechanisms

    PubMed Central

    Nath, Karl A.; Hebbel, Robert P.

    2015-01-01

    Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

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

    PubMed

    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.

  8. Genetic polymorphisms of the interleukin-4 receptor alpha gene are associated with an increasing risk and a poor prognosis of sporadic renal cell carcinoma in a Japanese population.

    PubMed

    Nakamura, Eijiro; Megumi, Yuzuru; Kobayashi, Takashi; Kamoto, Toshiyuki; Ishitoya, Satoshi; Terachi, Toshiro; Tachibana, Mitsuhiro; Matsushiro, Hisanori; Habuchi, Tomonori; Kakehi, Yoshiyuki; Ogawa, Osamu

    2002-08-01

    It has been suggested that the immune system of the host may be capable of modulating the clinical course of renal cell carcinoma (RCC) patients. In fact, the amount of Th2 cytokines such as interleukin (IL)-4 and IL-10 in the serum of patients has been found to be an important predictor of poor prognosis. Recently, it was reported that genetic polymorphisms of the IL-4 receptor alpha (IL-4Ralpha) gene affect the strength of signaling through the receptor. In addition, these same polymorphisms were found to be associated with an increased risk of atopy by causing Th2-dominated responses of the host. The significance of the polymorphisms on the incidence and prognosis in sporadic RCC patients were examined to clarify the role of IL-4 as well as that of the Th1/Th2 immune system in this disease. A case-control study was performed with 143 sporadic RCCs in a Japanese population and 205 Japanese controls. Logistic regression models were also used to assess the genetic effects on prognosis. The frequencies of variant alleles that enhance signaling of IL-4 were significantly related to an increased risk of RCC. Furthermore, multivariate regression analysis showed that the genotype of the IL-4R gene was an independent prognostic factor for cause-specific survival (P = 0.018) together with M classification (P = 0.0002) and histopathological grade (P = 0.044). The present findings show that the preferential Th2-type response to tumors was associated with a poorer prognosis and suggest that polymorphisms of the IL-4Ralpha gene may serve as useful genetic markers for assessing the risk of the development and progression of RCC.

  9. Renal abnormalities in sickle cell disease.

    PubMed

    Ataga, K I; Orringer, E P

    2000-04-01

    Sickle cell anemia and the related hemoglobinopathies are associated with a large spectrum of renal abnormalities. The patients have impaired urinary concentrating ability, defects in urinary acidification and potassium excretion, and supranormal proximal tubular function. The latter is manifest by increased secretion of creatinine and by reabsorption of phosphorus and beta(2)-microglobulin. Young patients with sickle cell disease (SCD) have supranormal renal hemodynamics with elevations in both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). These parameters decrease with age as well as following the administration of prostaglandin inhibitors. Proteinuria, a common finding in adults with sickle cell disease, may progress to the nephrotic syndrome. Proteinuria, hypertension, and increasing anemia predict end-stage renal disease (ESRD). While ESRD can be managed by dialysis and/or renal transplantation, there may be an increased rate of complications in renal transplant recipients with SCD. Hematuria is seen in individuals with all of the SCDs as well as with sickle cell trait. In most cases the etiology of the hematuria turns out to be benign. However, there does appear to be an increased association between SCD and renal medullary carcinoma. Therefore, those SCD patients who present with hematuria should initially undergo a thorough evaluation in order to exclude this aggressive neoplasm. Papillary necrosis may occur due to medullary ischemia and infarction. Erythropoietin levels are usually lower than expected for their degree of anemia and decrease further as renal function deteriorates. An abnormal balance of renal prostaglandins may be responsible for some of the changes in sickle cell nephropathy. Acute renal failure is a component of the acute multiorgan failure syndrome (MOFS). Finally, progression of sickle cell nephropathy to ESRD may be slowed by adequate control of hypertension and proteinuria. However, the prevention of the

  10. GNAS1 (Gαs) gene T393C polymorphism and renal cell carcinoma risk in a North Indian population: a case-control study.

    PubMed

    Arjumand, Wani; Ahmad, Shiekh Tanveer; Nafees, Sana; Ali, Nemat; Rashid, Summya; Seth, Amlesh; Sultana, Sarwat

    2012-09-01

    Heterotrimeric G protein α-subunit Gαs is required for activation of adenylyl cyclase and generation of cyclic adenosine monophosphate (cAMP) in cells and plays a key role in multiple signal transduction pathways, linked to proapoptotic processes in cancer cells. This study investigated whether Gαs gene polymorphism was associated with increased renal cell carcinoma (RCC) risk in the North Indian population. In the present study, genotyping of GNAS1 gene in 196 RCC cases and 250 healthy controls was performed via polymerase chain reaction-restriction fragment length polymorphism. The frequency of homozygous genotype CC was 29.6%, heterozygous TC was 51.5%, and homozygous TT was 18.9% in cases, whereas in controls it was 16.8%, 50.8%, and 32.4%, respectively; thus, there was a significant difference between the two groups (p=0.0001) in the univariate model. Further, multivariate analysis also demonstrated significant association of CC genotype with RCC risk (p=0.002). The high-risk genotype CC of GNAS1 gene showed threefold increase in risk to RCC relative to the TT genotype (unadjusted odds ratio [OR]=3.023, 95% confidence interval [CI]: 1.734-5.270). Whereas multivariate analysis showed a twofold increase in RCC risk among the CC genotype compared with the TT genotype (adjusted OR=2.181, 95% CI: 1.344-3.538). The C allele frequency was found to be significantly higher in RCC patients (55.3%) than in controls (42.2%) as compared with the T allele frequency that was 44.64% in RCC cases and 57.8% in controls. Moreover, patients with the CC genotype showed the worst prognosis in terms of the highest frequency of individuals having higher stages of RCC, but did not show any association with histological grade. Our results suggest that a T393C SNP could be considered as a genetic marker implicated in the pathogenesis of RCC.

  11. Renal cell cancer among African Americans: an epidemiologic review.

    PubMed

    Lipworth, Loren; Tarone, Robert E; McLaughlin, Joseph K

    2011-04-12

    Incidence rates for renal cell cancer, which accounts for 85% of kidney cancers, have been rising more rapidly among blacks than whites, almost entirely accounted for by an excess of localized disease. This excess dates back to the 1970s, despite less access among blacks to imaging procedures in the past. In contrast, mortality rates for this cancer have been virtually identical among blacks and whites since the early 1990s, despite the fact that nephrectomy rates, regardless of stage, are lower among blacks than among whites. These observations suggest that renal cell cancer may be a less aggressive tumor in blacks. We have reviewed the epidemiology of renal cell cancer, with emphasis on factors which may potentially play a role in the observed differences in incidence and mortality patterns of renal cell cancer among blacks and whites. To date, the factors most consistently, albeit modestly, associated with increased renal cell cancer risk in epidemiologic studies among whites--obesity, hypertension, cigarette smoking--likely account for less than half of these cancers, and there is virtually no epidemiologic evidence in the literature pertaining to their association with renal cell cancer among blacks. There is a long overdue need for detailed etiologic cohort and case-control studies of renal cell cancer among blacks, as they now represent the population at highest risk in the United States. In particular, investigation of the influence on renal cell cancer development of hypertension and chronic kidney disease, both of which occur substantially more frequently among blacks, is warranted, as well as investigations into the biology and natural history of this cancer among blacks.

  12. Tubulocystic Renal Cell Carcinoma: A Great Imitator

    PubMed Central

    Banerjee, Indraneel; Yadav, Sher Singh; Tomar, Vinay; Yadav, Suresh; Talreja, Shyam

    2016-01-01

    Tubulocystic renal cell carcinoma (TCRC) is a rare renal tumor. Patients are usually asymptomatic; it is usually detected incidentally, during imaging studies for Bosniak type III and type IV renal cysts. These tumors rarely metastasize. The role of targeted therapy in such rare tumors is still controversial. We report a case of TCRC initially presented as a Bosniak type II renal cyst and was discovered ultimately to be a metastatic disease. This type of presentation might broaden our understanding of this rare disease. PMID:27601972

  13. The renal microenvironment modifies dendritic cell phenotype.

    PubMed

    Chessa, Federica; Mathow, Daniel; Wang, Shijun; Hielscher, Thomas; Atzberger, Ann; Porubsky, Stefan; Gretz, Norbert; Burgdorf, Sven; Gröne, Hermann-Josef; Popovic, Zoran V

    2016-01-01

    Renal dendritic cells are a major component of the renal mononuclear phagocytic system. In the renal interstitium, these cells are exposed to an osmotic gradient, mainly sodium, whose concentration progressively increases towards inner medulla. Renal allograft rejection affects predominantly the cortex, suggesting a protective role of the renal medullary micromilieu. Whether osmolar variations can modulate the function of renal dendritic cells is currently undefined. Considering the central role of dendritic cells in promoting allorejection, we tested whether the biophysical micromilieu, particularly the interstitial osmotic gradient, influences their alloreactivity. There was a progressive depletion of leukocytes towards the medulla of homeostatic kidney. Only macrophages opposed this tendency. Flow cytometry of homeostatic and post-transplant medullary dendritic cells revealed a switch towards a macrophage-like phenotype. Similarly, bone marrow-derived dendritic cells developed ex vivo in sodium chloride-enriched medium acquired a M2-like signature. Microarray analysis of allotransplant dendritic cells posed a medullary downregulation of genes mainly involved in alloantigen recognition. Gene expression profiles of both medullary dendritic cells and bone marrow-derived dendritic cells matured in hyperosmolar medium had an overlap with the macrophage M2 signature. Thus, the medullary environment inhibits an alloimmune response by modulating the phenotype and function of dendritic cells.

  14. Uptake of Polymyxin B into Renal Cells

    PubMed Central

    Abdelraouf, Kamilia; Chang, Kai-Tai; Yin, Taijun; Hu, Ming

    2014-01-01

    Polymyxin B is increasingly used as a treatment of last resort against multidrug-resistant Gram-negative infections. Using a mammalian kidney cell line, we demonstrated that polymyxin B uptake into proximal tubular epithelial cells was saturable and occurred primarily through the apical membrane, suggesting the involvement of transporters in the renal uptake of polymyxin B. Megalin might play a role in the uptake and accumulation of polymyxin B into renal cells. PMID:24733472

  15. [Treatment of metastatic renal cell carcinoma].

    PubMed

    Thuret, R; Maurin, C; Sun, M; Perrotte, P; Karakiewicz, P I

    2011-04-01

    The median survival of patients with metastatic renal cell carcinoma (mRCC) increased from 10 to more than 40 months since the advent of targeted therapy. The transformation of mRCC from an initially lethal disease to a more favorable entity, albeit incurable, occurred with the transition from best supportive care, to cytokines, to finally sequential targeted therapies. Sunitinib and bevacizumab (level 1b) represent the first-line standard of care for patients with clear-cell mRCC vs temsirolimus (level 2) for those with high-risk features. Additionally, exploratory analyses of the temsirolimus data indicate important benefits for those with nonclear-cell mRCC histological subtypes. In second-line, everolimus proved its efficacy (level 1b). Nonetheless, sunitinib and sorafenib are also effective for nonclear-cell histological subtypes and after failure of other first-line treatment. The PFS benefits of first- and subsequent treatment-lines were confirmed in virtually all subgroup analyses. Potential survival benefits can be derived from cytoreductive nephrectomy (CNT), as was shown for cytokines in the general population, in sunitinib and bevacizumab-exposed patients. Phase III studies are ongoing to address the importance of CNT. This information is crucial to ensure timely delivery of a combination of medical and surgical therapies in this patient population.

  16. A Bioartificial Renal Tubule Device Embedding Human Renal Stem/Progenitor Cells

    PubMed Central

    Sciancalepore, Anna Giovanna; Sallustio, Fabio; Girardo, Salvatore; Gioia Passione, Laura; Camposeo, Andrea; Mele, Elisa; Di Lorenzo, Mirella; Costantino, Vincenzo; Schena, Francesco Paolo; Pisignano, Dario

    2014-01-01

    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. PMID:24498117

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

    PubMed

    Sciancalepore, Anna Giovanna; Sallustio, Fabio; Girardo, Salvatore; Gioia Passione, Laura; Camposeo, Andrea; Mele, Elisa; Di Lorenzo, Mirella; Costantino, Vincenzo; Schena, Francesco Paolo; Pisignano, Dario

    2014-01-01

    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.

  18. Apigenin inhibits renal cell carcinoma cell proliferation.

    PubMed

    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.

  19. Sunitinib benefits patients with renal cell carcinoma

    Cancer.gov

    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.

  20. Perioperative Considerations in Metastatic Renal Cell Carcinoma

    PubMed Central

    Flavin, Kate; Vasdev, Nikhil; Ashead, Jim; Lane, Tim; Hanbury, Damian; Nathan, Paul; Gowrie-Mohan, Shanmugasundaram

    2016-01-01

    Patients with metastatic renal cell carcinoma are complex, with the potential for significant complications, and require extensive pre-, peri-, and postoperative management. This article discusses, in depth, the necessary considerations in the treatment of these patients. PMID:27833463

  1. Renal Cell Carcinoma Metastasized to Pagetic Bone

    PubMed Central

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

    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. PMID:27660736

  2. Percutaneous Cryoablation for Renal Cell Carcinoma

    PubMed Central

    Georgiades, Christos

    2015-01-01

    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.

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

    PubMed

    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 < .01). The median peak creatinine level was 1.6 mg/dl after treatment (p < .01). Percentage volumes of the irradiated kidney receiving at least 10 Gy (V10, p = 0.03), V20 (p < .01), V30(p < .01), V40 (p = 0.01), mean irradiated kidney dose (p < .01), and magnitude of overlap between PTV and kidney volume (p = 0.03) were significantly correlated with post-treatment irradiated kidney volume in percent, and V20-V30 had strong correlation (r < -0.70, p < .01). Patients with implanted fiducial markers showed a significantly lower ratio of renal 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.

  4. Familial renal cell carcinoma: clinical and molecular genetic aspects

    PubMed Central

    Maher, E.R.; Yates, J.R.W.

    1991-01-01

    Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial cases are infrequent. Riches (1963) and Griffin et al. (1984) in a population-based case-control study found a family history of renal cell carcinoma in 2.4% of affected patients compared to 1.4% of controls. Nevertheless the importance of inherited tumours in clinical practice and medical research is disproportionate to their frequency. In clinical practice recognition of familial RCC can provide opportunities to prevent morbidity and mortality by appropriate screening. In medical research recent advances in molecular genetics offer the prospect of isolating the genes involved in the pathogenesis of familial RCC and of the more common sporadic cases. In this article we review the clinical and molecular genetics of inherited renal cell carcinoma (adenocarcinoma or hypernephroma). PMID:1997093

  5. Clear cell papillary renal cell carcinoma, renal angiomyoadenomatous tumor, and renal cell carcinoma with leiomyomatous stroma relationship of 3 types of renal tumors: a review.

    PubMed

    Hes, Ondrej; Compérat, Eva Maria; Rioux-Leclercq, Nathalie

    2016-04-01

    Renal angiomyoadenomatous tumor has been described in 2000, followed by description of clear cell papillary renal cell carcinoma in 2006. Discussions about possible relationship of both tumors were published since their description. The main differential diagnostic feature was considered presence/absence of fibroleiomyomatous stroma-relationship of renal angiomyoadenomatous tumor in stroma-rich tumors. However, it was shown that stroma is reactive and nonneoplastic by its nature and that all other histologic, immunohistochemical, and molecular-genetic features of both entities are identical. In upcoming World Health Organization classification of renal tumors (2016), both lesions are considered as a single entity (clear cell papillary renal cell carcinoma [CCPRCC]). Most published cases followed the benign/indolent clinical course. In addition, most tumors has normal status of VHL gene (methylation, LOH 3p, mutations); however, CCPRCC was referred in patients with VHL syndrome. Another issue covered by this review is possible relationship of CCPRCC and "renal cell carcinoma with leiomyomatous stroma" (RCCLS). Renal cell carcinoma with leiomyomatous stroma shows clear cell cytology and abundant leiomyomatous stroma. Some of RCCLS are positive for cytokeratin 7; some are negative. Similar situation exists for relation of RCCLS and VHL gene abnormalities. It is so far unclear whether any relation between CCPRCC and RCCLS exists. From all published studies, it seems that these tumors are less likely related to each other.

  6. Interdigitating reticulum cells in human renal grafts.

    PubMed

    Wakabayashi, T; Onoda, H

    1991-01-01

    Seventeen human renal graft biopsies taken 1 h to 50 days after transplantation and 3 human renal non-graft biopsies (2 minimal change and 1 non-tumour portion of angiomyolipoma) were investigated with immunoelectron microscopy in order to identify interdigitating reticulum cells (IDC) or dendritic cells (DC) in renal tissues. The antibodies used consisted of a rabbit polyclonal antibody of antihuman S100 beta protein, mouse monoclonal antibodies of antihuman HLA-DR, anti-CD3, and anti-CD1a. IDC or DC were identified in 11 renal grafts. They were found both in the glomerular and interstitial (peritubular) capillary lumens but not in the interstitium of 1 case: both were present in the interstitial capillary lumens and interstitium of another case, and in the interstitium only of 9 cases. In the remaining 6 grafts and 3 non-grafts they were not detected. These 6 grafts and 3 non-grafts did not show any pathological change except for foot process fusion of the glomerular epithelia in 2 cases of minimal change. These findings suggest that IDC or DC are not normally present in human renal tissues. The presence of the cell in the glomerular and peritubular capillary lumens of a biopsy taken after 1 h and their presence in the interstitial capillary lumens of another graft biopsy, suggest that the IDC or DC in human renal grafts are derived from recipients, not donors, and that they migrate from the circulating blood toward the interstitium.

  7. Renal cell carcinoma: Evolving and emerging subtypes

    PubMed Central

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-01-01

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  8. Chromophobe renal cell carcinoma with sarcomatoid transformation.

    PubMed

    Abrahams, Neil A; Ayala, Alberto G; Czerniak, Bogdan

    2003-10-01

    We present a rare case of a chromophobe renal cell carcinoma that progressed to a high-grade spindle cell sarcoma. The tumor affected a 50-year-old man who had presented with right upper quadrant discomfort and hematuria and subsequently underwent a right radical nephrectomy. Microscopically, the tumor was composed of two distinct components, a chromophobe renal cell carcinoma and a sarcomatoid component. The sarcomatoid component had exhibited aggressive behavior by spreading to a regional lymph node. This case report shows that chromophobe carcinoma can develop a sarcomatoid transformation with a high propensity for invasive growth and metastasis.

  9. Microwave treatment of renal cell carcinoma adjacent to renal sinus.

    PubMed

    Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

    2016-11-01

    To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4cm (100%, 29/29) and RCCs >4cm (75%, 9/12, p=0.021). During the median follow-up of 37.6 (range, 3.0-97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. US-guided percutaneous MWA appears to be a promising method for RCCs adjacent to renal sinus, especially for tumors ≤4cm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Renal arteriography

    MedlinePlus

    Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

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

    PubMed

    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.

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

    PubMed

    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.

  13. Intraventricular metastatic clear cell renal carcinoma.

    PubMed

    Sava, I; Sava, Anca; Şapte, Elena; Mihailov, Claudia; Dumitrescu, Gabriela; Poeată, I; Sava, Florina; Haba, Danisia

    2013-01-01

    Intraventricular tumors represent a diagnostic problem, due to a wide range of differential diagnosis, with an important variability of tumoral histological types in adult and pediatric population. Patient, Our case is represented by a patient, aged 48 years, without any history of significant personal pathology, accusing nausea, vomiting, and intensive headache. In the morning, he became confused, having hallucinations for a short period of time, and has accused drowsiness for several weeks. Imaging (CT and MRI) shows a neoformation in the third ventricle, accompanied by bilateral lateral ventricles dilatation, with predominantly annular enhancement. During surgery, through the middle third transcallosal interhemispheric approach, it was revealed a reddish, well-demarcated intraventricular mass, well vascularized and with a firm consistency. Final pathologic diagnosis was metastatic clear cell renal carcinoma. Initial postoperative evolution was good, and then neurological and respiratory condition worsened as a bronchopneumonia lead to patient's death in 12 days after surgery. Clear cell carcinoma metastasis located in the third ventricle should be taken into consideration for patients presenting a single intraventricular lesion even they have no documented primary malignancy.

  14. Renal failure in sickle cell anemia.

    PubMed

    Wong, W Y; Elliott-Mills, D; Powars, D

    1996-12-01

    ESRD is a major complication in young adults with sickle cell anemia. As more patients with sickle cell anemia reach the third and fourth decades of life, the incidence of clinically apparent renal insufficiency will increase. As we understand the pathophysiology of renal damage and the effects of various therapies on the sickle renal vasculature, we can tailor specific management without further compromising already impaired renal function. Diagnostic clues must be recognized prior to the onset of irreversible damage, with appropriate intervention initiated at each age group. Bone marrow transplantation (BMT) is the only available cure for SCA at the present time. The demonstration that several distinct haplotypes of the beta s gene cluster on chromosome 11 influence the clinical expression of sickle cell anemia may be useful in delineating children who are at high risk for severe disease, and hence candidates for such hazardous therapeutic interventions as BMT prior to onset of clinically discernable disease. Current BMT preparative regimens can produce renal cortical and pulmonary toxicity, posing a patient selection problem in those cases in which the vasculopathy of the major organs is at an early stage and might be potentially repairable. Gene therapy without toxic preparative regimens is the ultimate answer. The challenge for the near future is the development of effective early therapeutic intervention during childhood and young adulthood.

  15. Local anesthetics induce human renal cell apoptosis.

    PubMed

    Lee, H Thomas; Xu, Hua; Siegel, Cory D; Krichevsky, Igor E

    2003-01-01

    Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Local anesthetics induce apoptosis in neuronal and lymphocytic cell lines. We examined the effects of chronic (48 h) local anesthetic treatment (lidocaine, bupivacaine and tetracaine) on human proximal tubular (HK-2) cells. Apoptosis induction was assessed by detecting poly(ADP)-ribose polymerase fragmentation, caspase activation, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, DNA laddering and by cellular morphology. Cell death was quantified by measuring neutral red dye uptake and lactate dehydrogenase released into the cell culture medium. All 3 local anesthetics caused concentration-dependent cell death, induced HK-2 cell apoptosis and potentiated TNF-alpha induced apoptosis. Local anesthetics induced HK-2 cell apoptosis by activation of caspases 3, 6, 7, 8 and 9. ZVAD-fmk, a pan-caspase inhibitor, blocked the local anesthetic induced HK-2 cell apoptosis. Local anesthetics also inhibited the activities of anti-apoptotic kinases protein kinase B (Akt) and extracellular signal regulated mitrogen-activated protein kinase. Local anesthetic's pro-apoptotic effects are independent of sodium channel inhibition as tetrodotoxin, a selective voltage-gated sodium channel blocker, failed to mimic local anesthetic-mediated induction or potentiation of HK-2 cell apoptosis. We conclude that local anesthetics induce human renal cell apoptotic signaling by caspase activation and via inhibition of pro-survival signaling pathways.

  16. Contrast agents and renal cell apoptosis.

    PubMed

    Romano, Giulia; Briguori, Carlo; Quintavalle, Cristina; Zanca, Ciro; Rivera, Natalia V; Colombo, Antonio; Condorelli, Gerolama

    2008-10-01

    Contrast media (CM) induce a direct toxic effect on renal tubular cells. This toxic effect may have a role in the pathophysiology of contrast nephropathy. We evaluated (i) the cytotoxicity of CM [both low-osmolality (LOCM) and iso-osmolality (IOCM)], of iodine alone, and of an hyperosmolar solution (mannitol 8%) on human embryonic kidney (HEK 293), porcine proximal renal tubular (LLC-PK1), and canine Madin-Darby distal tubular renal (MDCK) cells; and (ii) the effectiveness of various antioxidant compounds [n-acetylcysteine (NAC), ascorbic acid and sodium bicarbonate] in preventing CM cytotoxicity. The cytotoxicity of CM was assessed at different time points, with different methods: cell viability, DNA laddering, flow cytometry, and caspase activation. Both LOCM and IOCM produced a concentration- and time-dependent increase in cell death as assessed by the different methods. On the contrary, iodine alone and hyperosmolar solution did not induce any significant cytotoxic effect. There was not any significant difference in the cytotoxic effect between LOCM and IOCM. Furthermore, both LOCM and IOCM caused a marked increase in caspase-3 and -9 activities and poly(ADP-ribose) fragmentation, while no effect on caspase-8/-10 was observed, thus indicating that the CM activated apoptosis mainly through the intrinsic pathway. Both CM induced an increase in protein expression levels of pro-apoptotic members of the Bcl2 family (Bim and Bad). NAC and ascorbic acid but not sodium bicarbonate had a dose-dependent protective effect on renal cells after 3 h incubation with high dose (200 mg iodine/mL) of both LOCM and IOCM. Both LOCM and IOCM induce a dose-dependent renal cell apoptosis. NAC and ascorbic acid but not sodium bicarbonate prevent this contrast-induced apoptosis.

  17. Renal Replacement Therapy in the Elderly Population

    PubMed Central

    Berger, Joseph R.

    2012-01-01

    Summary ESRD has become an important problem for elderly patients. The segment of the ESRD population age 65 years or older has grown considerably, and this growth is expected to accelerate in coming years. Nephrologists caring for the elderly with advanced kidney disease will encounter patients with comorbid conditions common in younger patients, as well as physical, psychological, and social challenges that occur with increased frequency in the aging population. These challenging factors must be addressed to help inform decisions regarding the option to initiate dialysis, the choice of dialysis modality, whether to pursue kidney transplantation, and end-of-life care. This article will highlight some common problems encountered by elderly patients with ESRD and review data on the clinical outcomes of elderly patients treated with different modalities of dialysis, outcomes of kidney transplantation in the elderly, and nondialytic management of CKD stage 5. PMID:22516288

  18. Concurrent Bilateral Renal Angiomyolipoma and Renal Cell Carcinoma in a Patient With Tuberous Sclerosis Complex

    PubMed Central

    Khallouk, Abdelhak; Ahallal, Younes; Doublali, Mbarek; Tazi, Mohamed Fadl; Mellas, Soufiane; el Fassi, Mohamed Jamal; Farih, Moulay Hassan

    2009-01-01

    Renal angiomyolipomas (AMLs) are often associated with tuberous sclerosis. These tumors are predominantly benign, although malignant forms do exist and are known to be associated with renal cell carcinoma. This case report describes a patient with tuberous sclerosis and massive bilateral AML. Total right nephrectomy was performed; histopathologic examination revealed the coexistence of AML and clear cell renal carcinoma in the same kidney. Because differentiation between renal cell carcinoma and AML with minimal or no fat component can be difficult, an accurate diagnosis is critical in the management of renal AML. PMID:20111634

  19. Concurrent bilateral renal angiomyolipoma and renal cell carcinoma in a patient with tuberous sclerosis complex.

    PubMed

    Khallouk, Abdelhak; Ahallal, Younes; Doublali, Mbarek; Tazi, Mohamed Fadl; Mellas, Soufiane; El Fassi, Mohamed Jamal; Farih, Moulay Hassan

    2009-01-01

    Renal angiomyolipomas (AMLs) are often associated with tuberous sclerosis. These tumors are predominantly benign, although malignant forms do exist and are known to be associated with renal cell carcinoma. This case report describes a patient with tuberous sclerosis and massive bilateral AML. Total right nephrectomy was performed; histopathologic examination revealed the coexistence of AML and clear cell renal carcinoma in the same kidney. Because differentiation between renal cell carcinoma and AML with minimal or no fat component can be difficult, an accurate diagnosis is critical in the management of renal AML.

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

    PubMed

    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.

  1. Essential but differential role for CXCR4 and CXCR7 in the therapeutic homing of human renal progenitor cells.

    PubMed

    Mazzinghi, Benedetta; Ronconi, Elisa; Lazzeri, Elena; Sagrinati, Costanza; Ballerini, Lara; Angelotti, Maria Lucia; Parente, Eliana; Mancina, Rosa; Netti, Giuseppe Stefano; Becherucci, Francesca; Gacci, Mauro; Carini, Marco; Gesualdo, Loreto; Rotondi, Mario; Maggi, Enrico; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

    2008-02-18

    Recently, we have identified a population of renal progenitor cells in human kidneys showing regenerative potential for injured renal tissue of SCID mice. We demonstrate here that among all known chemokine receptors, human renal progenitor cells exhibit high expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7. In SCID mice with acute renal failure (ARF), SDF-1 was strongly up-regulated in resident cells surrounding necrotic areas. In the same mice, intravenously injected renal stem/progenitor cells engrafted into injured renal tissue decreased the severity of ARF and prevented renal fibrosis. These beneficial effects were abolished by blocking either CXCR4 or CXCR7, which dramatically reduced the number of engrafting renal progenitor cells. However, although SDF-1-induced migration of renal progenitor cells was only abolished by an anti-CXCR4 antibody, transendothelial migration required the activity of both CXCR4 and CXCR7, with CXCR7 being essential for renal progenitor cell adhesion to endothelial cells. Moreover, CXCR7 but not CXCR4 was responsible for the SDF-1-induced renal progenitor cell survival. Collectively, these findings suggest that CXCR4 and CXCR7 play an essential, but differential, role in the therapeutic homing of human renal progenitor cells in ARF, with important implications for the development of stem cell-based therapies.

  2. Hereditary leiomyomatosis and renal cell carcinoma

    PubMed Central

    Schmidt, Laura S; Linehan, W Marston

    2014-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal-dominant hereditary syndrome, which is caused by germline mutations in the FH gene that encodes the tricarboxylic acid cycle enzyme fumarate hydratase (FH). HLRCC patients are predisposed to develop cutaneous leiomyomas, multiple, symptomatic uterine fibroids in young women resulting in early hysterectomies, and early onset renal tumors with a type 2 papillary morphology that can progress and metastasize, even when small. Since HLRCC-associated renal tumors can be more aggressive than renal tumors in other hereditary renal cancer syndromes, caution is warranted, and surgical intervention is recommended rather than active surveillance. At-risk members of an HLRCC family who test positive for the familial germline FH mutation should undergo surveillance by annual magnetic resonance imaging from the age of 8 years. Biochemical studies have shown that FH-deficient kidney cancer is characterized by a metabolic shift to aerobic glycolysis. It is hoped that through ongoing clinical trials evaluating targeted molecular therapies, an effective form of treatment for HLRCC-associated kidney cancer will be developed that will offer an improved prognosis for individuals affected with HLRCC-associated kidney cancer. PMID:25018647

  3. Diagnostic value of routine bone scintigraphy renal imaging in renal cell carcinoma

    SciTech Connect

    Chancellor, M.B.; Konnak, J.W.; Grossman, H.B.

    1989-05-01

    Technetium-99m-phosphate compounds used in bone scanning are excreted by the kidney, and excellent renal images can be obtained on routine bone scintigrams. The preoperative bone scans of 49 patients who underwent radical nephrectomy for renal cell carcinoma between 1981 and 1985 were reviewed for renal imaging. Ninety-four percent of the patients had abnormal bone scan renal images (82% had focal decreased uptake, and 12% had focal increased uptake). Six percent of the renal images were symmetrical bilaterally. When bone scans are employed in the postoperative follow-up of patients with renal cancer, they can be used to assess the status of the remaining kidney.

  4. End stage renal disease serum contains a specific renal cell growth factor

    SciTech Connect

    Klotz, L.H.; Kulkarni, C.; Mills, G. )

    1991-01-01

    End stage renal disease (ESRD) kidneys display abnormal growth characterized by a continuum of cystic disease, adenoma and carcinoma. This study evaluates the hypothesis that serum of patients with ESRD contains increased amounts of a growth factor which specifically induces proliferation of renal cells. ESRD sera compared to sera from normal controls induced a two to three-fold increase in the proliferative rate of renal cell carcinoma cell lines and normal kidney explants compared to cell lines from other sites. The increased proliferative activity of ESRD sera on renal cells was paralleled by an increase in cytosolic free calcium. The growth factor activity was encoded by a polypeptide of between 15 and 30 kd. The activity of ESRD sera on renal cells was not mimicked or inhibited by epidermal growth factor, basic fibroblast growth factor and platelet derived growth factor indicating that the renal cell specific growth factor activity in ESRD is different from these factors.

  5. Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population

    PubMed Central

    Qu, Yuanyuan; Gu, Chengyuan; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

    2016-01-01

    This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH-positive group were 13.0 months (95% CI, 8.4–17.6 months) and 50.0 months (95% CI, 27.6–72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis. PMID:26880493

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

    PubMed

    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.

  7. STUDIES ON RENAL JUXTAGLOMERULAR CELLS

    PubMed Central

    Hartroft, Phyllis Merritt; Hartroft, W. Stanley

    1953-01-01

    Accumulation of granules in the juxtaglomerular cells occurred in rats which were maintained for 5 to 6 weeks on a diet low in sodium, chloride. Cytological evidence suggests that this was probably a storage phase of secretion following a decrease in the rate of liberation of the granules. Administration of DCA (desoxycorticosterone acetate) to salt-deficient rats did not alter this appearance of the juxtaglomerular cells. Two per cent sodium chloride taken in the drinking water consumed for 4 weeks by similar animals caused degranulation of the juxtaglomerular cells. This effect was enhanced by DCA. DCA administered to animals on a normal salt intake produced a lesser degree of degranulation. Cytological changes in degranulated cells suggested that these represent a stage of hyperactivity in the secretory cycle produced by an increase in the rate of liberation of granules. A hypothesis is suggested that the juxtaglomerular cells are involved in the hormonal regulation of sodium metabolism and/or blood pressure. PMID:13052809

  8. Simultaneous infiltration of polyfunctional effector and suppressor T cells into renal cell carcinomas.

    PubMed

    Attig, Sebastian; Hennenlotter, Jörg; Pawelec, Graham; Klein, Gerd; Koch, Sven D; Pircher, Hanspeter; Feyerabend, Susan; Wernet, Dorothee; Stenzl, Arnulf; Rammensee, Hans-Georg; Gouttefangeas, Cécile

    2009-11-01

    Renal cell carcinoma is frequently infiltrated by cells of the immune system. This makes it important to understand interactions between cancer cells and immune cells so they can be manipulated to bring clinical benefit. Here, we analyze subsets and functions of T lymphocytes infiltrating renal cell tumors directly ex vivo following mechanical disaggregation and without any culture step. Subpopulations of memory and effector CD4(+) Th1, Th2, and Th17 and CD8(+) Tc1 cells were identified based on surface phenotype, activation potential, and multicytokine production. Compared with the same patient's peripheral blood, T lymphocytes present inside tumors were found to be enriched in functional CD4(+) cells of the Th1 lineage and in effector memory CD8(+) cells. Additionally, several populations of CD4(+) and CD8(+) regulatory T cells were identified that may synergize to locally dampen antitumor T-cell responses.

  9. Giant kidney worms in a patient with renal cell carcinoma.

    PubMed

    Kuehn, Jemima; Lombardo, Lindsay; Janda, William M; Hollowell, Courtney M P

    2016-03-07

    Dioctophyma renale (D. renale), or giant kidney worms, are the largest nematodes that infect mammals. Approximately 20 cases of human infection have been reported. We present a case of a 71-year-old man with a recent history of unintentional weight loss and painless haematuria, passing elongated erythematous tissue via his urethra. CT revealed a left renal mass with pulmonary nodules and hepatic lesions. On microscopy, the erythematous tissue passed was identified as D. renale. On subsequent renal biopsy, pathology was consistent with renal cell carcinoma. This is the first reported case of concomitant D. renale infection and renal cell carcinoma, and the second reported case of D. renale infection of the left kidney alone.

  10. Genomics and epigenomics of renal cell carcinoma.

    PubMed

    Maher, Eamonn R

    2013-02-01

    Kidney cancer accounts for about 2% of all cancers and worldwide >250,000 new cases of kidney cancer are diagnosed each year. Renal cell carcinoma (RCC) is the most common form of adult kidney cancer and this review describes our current knowledge of the genetic and epigenetic basis of sporadic RCC. Though to date major advances in understanding the underlying the molecular basis of renal cell carcinoma (RCC) have often been derived from studies of rare familial forms of renal cell carcinoma, large-scale genomic and epigenomic studies of sporadic tumours are beginning to provide clearer pictures of the genomic and epigenomic landscape of RCC and the key pathways implicated in the initiation and progression of the disease. Although current knowledge of the molecular pathogenesis of RCC is incomplete, and mostly relates to clear cell (conventional) RCC, the next five years will see an unprecedented flood of genomic and epigenomic data and the key future challenges will relate to the utilisation of this data to develop novel genetic and epigenetic markers for diagnosis and prognosis and to develop novel targeted therapies in order to enable an age of personalised medicine.

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

    PubMed

    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.

  12. Hereditary Papillary Renal Cell Carcinoma

    MedlinePlus

    ... removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed ... question. The parents can then choose to transfer embryos that do not have the mutation. PGD has ...

  13. Thyroid Hormones as Renal Cell Cancer Regulators

    PubMed Central

    Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

    2016-01-01

    It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma. PMID:27034829

  14. Diabetes and Risk of Renal Cell Carcinoma

    PubMed Central

    Habib, Samy L; Prihoda, Thomas J; Luna, Maria; Werner, Sherry A

    2012-01-01

    Background and objectives: There is evidence that the incidence of solid tumors is markedly increased in patients with diabetes mellitus. In the current study, we investigate the association between diabetes and renal cancer. Patients and Methods: A single-center retrospective analysis of 473 patients who underwent nephrectomy for renal cell carcinoma (RCC) was performed. Diabetic RCC patients were screened for age, gender, ethnicity, HgA1C, glucose levels and renal function. Results: Of the 473 cases with RCC, we identified 120 patients (25.4%) with a history of diabetes. The incidence of diabetes in RCC patients was higher in female than male subjects and in Hispanic compared to White and Other ethnic backgrounds. At diagnosis, the majority of diabetic RCC patients were 50-59 years of age. In diabetic RCC cases, clear cell type histology (92.0%), nuclear grade 2 (56.1%) and tumor size range from 1-5 cm (65.7%) were the most common in each category. Conclusion: Our findings indicate that diabetic RCC patients have a predominance of localized, small clear cell RCC. In addition, females with a history of RCC have a higher frequency of diabetes compared to males. This is the first report of clinical and histopathological features of RCC associated with diabetes. PMID:22232697

  15. Update on the medical treatment of metastatic renal cell carcinoma.

    PubMed

    Ravaud, Alain; Wallerand, Hervé; Culine, Stéphane; Bernhard, Jean-Christophe; Fergelot, Patricia; Bensalah, Karim; Patard, Jean-Jacques

    2008-08-01

    Metastatic renal cell carcinoma (mRCC) has long been treated only by immunotherapy with good results only in a small population of patients. In recent years, major improvements in treatment possibilities have occurred with the advent of anti-angiogenic drugs. In the past 2 yr, pivotal phase III trials have confirmed this major breakthrough by increasing the progression-free survival rates and/or overall survival rates provided by sunitinib, sorafenib, and bevacizumab, and more recently by the mTOR (mammalian target of rapamycin) inhibitors temsirolimus and everolimus. To update the previous review on smart drugs published in the European Journal in 2006 (Patard JJ, et al. Understanding the importance of smart drugs in renal cell carcinoma. Eur Urol 2006; 49:633-43). Critical review of published literature 2006-2008 (Pubmed website search words: renal cell carcinoma and/or targeted therapy and prospective trials) and more recent meeting abstracts (American Society of Clinical Oncology 2007). Quality assessment included prospective phase I-III trials and critical evaluations with low numbers of patients, retrospective analyses, and slide presentations of meeting abstracts. This review presents the current situation and provides more recent data on sequential treatment, the association of targeted drugs, and the treatment of non-clear-cell histologies. Treatment of mRCC with targeted therapy centers on at least two major pathways: angiogenesis and mTOR involving inhibiting drugs that may be used alone, in combination, or sequentially.

  16. Synchronous Renal Neoplasm: Clear Cell Renal Cell Carcinoma and Papillary Urothelial Carcinoma in the Same Kidney.

    PubMed

    Benavides-Huerto, Miguel Armando; Chávez-Valencia, Venice; Lagunas-Rangel, Francisco Alejandro

    2017-02-01

    Abdominal computed tomography in a 64 year-old male presenting hematuria showed two malignant tumors in the left kidney, thus radical nephrectomy was realized. In histological preparations a clear cell renal cell carcinoma and a papillary urothelial carcinoma were identified occurring synchronously, which is a rare occurrence having only about 50 cases reported in the literature.

  17. Renal Cell Carcinoma in Tuberous Sclerosis Complex

    PubMed Central

    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

  18. Honey induces apoptosis in renal cell carcinoma

    PubMed Central

    Samarghandian, Saeed; Afshari, Jalil Tavakkol; Davoodi, Saiedeh

    2011-01-01

    Background: The fact that antioxidants have several preventative effects against different diseases, such as coronary diseases, inflammatory disorders, neurologic degeneration, aging, and cancer, has led to the search for food rich in antioxidants. Honey has been used as a traditional food and medical source since ancient times. However, recently many scientists have been concentrating on the antioxidant property of honey. By use of human renal cancer cell lines (ACHN), we investigated the antiproliferative activity, apoptosis, and the antitumor activity of honey. Materials and Methods: The cells were cultured in Dulbecco’s modified Eagle’s medium with 10% fetal bovine serum treated with different concentrations of honey for 3 consecutive days. Cell viability was quantitated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were determined using Annexin-V-fluorescein isothiocyanate (FITC) by flow cytometry. Results: Honey decreased the cell viability in the malignant cells in a concentration- and time-dependent manner. The IC 50 values against the ACHN cell lines were determined as 1.7 ± 0.04% and 2.1 ± 0.03% μg/mL after 48 and 72 h, respectively. Honey induced apoptosis of the ACHN cells in a concentration-dependent manner, as determined by flow cytometry histogram of treated cells. Conclusion: It might be concluded that honey may cause cell death in the ACHN cells, in which apoptosis plays an important role. Most of the drugs used in the cancer treatment are apoptotic inducers, hence apoptotic nature of honey is considered vital. Therefore, it prompted us to investigate honey as a potential candidate for renal cancer treatment. PMID:21472079

  19. Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma

    PubMed Central

    Lopez, Jose Ignacio

    2016-01-01

    A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation. PMID:27158455

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

    PubMed

    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.

  1. A direct anatomical study of additional renal arteries in a Colombian mestizo population.

    PubMed

    Saldarriaga, B; Pérez, A F; Ballesteros, L E

    2008-05-01

    Traditional anatomy describes each kidney as receiving irrigation from a single renal artery. However, current literature reports great variability in renal blood supply, the number of renal arteries mentioned being the most frequently found variation. Such variation has great implications when surgery is indicated, such as in renal transplants, uroradiological procedures, renovascular hypertension, renal trauma and hydronephrosis. This article pretends to determine the frequency of additional renal arteries and their morphological expression in Colombian population in a cross-sectional study. A total of 196 of renal blocks were analysed from autopsies carried out in the Bucaramanga Institute of Forensic Medicine, Colombia; these renal blocks were processed by the injection- corrosion technique. The average age of the people being studied was 33.8 +/- 15.6 years; 85.4% of them were male and the rest female. An additional renal artery was found in 22.3% of the whole population and two additional ones were found in 2.6% of the same sample. The additional renal artery was most frequently found on the left side. The additional artery arose from the aorta's lateral aspect (52.4%); these additional arteries usually entered the renal parenchyma through the hilum. No difference was established according to gender. Nearly a third of the Colombian population presents one additional renal artery and about 3% of the same population presents two additional renal arteries. Most of them reached the kidney through its hilar region.

  2. Isolation and characterization of cancer stem cells in renal cell carcinoma.

    PubMed

    Lucarelli, Giuseppe; Galleggiante, Vanessa; Rutigliano, Monica; Vavallo, Antonio; Ditonno, Pasquale; Battaglia, Michele

    2015-01-01

    Recently, several studies have investigated the presence of cancer stem cells in kidney cancer, performed characterization, and compared their profile with the normal stem cell counterparts. CD133, alone or in combination with other molecular markers, has been used to isolate normal and cancer stem cells from different sources, including renal carcinoma; however, it is still a matter of debate whether CD133+ cells really represent the main tumorigenic population within the heterogeneous pool of cancer cells that characterize this tumor. In this review, we summarize and discuss the current findings related to cancer stem cells isolation in renal cell carcinoma, focusing on controversies about their origin and the identification of a specific marker.

  3. Clear cell papillary renal cell carcinoma: a review.

    PubMed

    Kuroda, Naoto; Ohe, Chisato; Kawakami, Fumi; Mikami, Shuji; Furuya, Mitsuko; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Zhou, Ming; Petersson, Fredrik; López, José I; Hes, Ondrej; Michal, Michal; Amin, Mahul B

    2014-01-01

    The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type.

  4. Snail heterogeneity in clear cell renal cell carcinoma.

    PubMed

    Zaldumbide, Laura; Erramuzpe, Asier; Guarch, Rosa; Pulido, Rafael; Cortés, Jesús M; López, José I

    2016-03-08

    Intratumor heterogeneity may be responsible of the unpredictable aggressive clinical behavior that some clear cell renal cell carcinomas display. This clinical uncertainty may be caused by insufficient sampling, leaving out of histological analysis foci of high grade tumor areas. Although molecular approaches are providing important information on renal intratumor heterogeneity, a focus on this topic from the practicing pathologist' perspective is still pending. Four distant tumor areas of 40 organ-confined clear cell renal cell carcinomas were selected for histopathological and immunohistochemical evaluation. Tumor size, cell type (clear/granular), Fuhrman's grade, Staging, as well as immunostaining with Snail, ZEB1, Twist, Vimentin, E-cadherin, β-catenin, PTEN, p-Akt, p110α, and SETD2, were analyzed for intratumor heterogeneity using a classification and regression tree algorithm. Cell type and Fuhrman's grade were heterogeneous in 12.5 and 60 % of the tumors, respectively. If cell type was homogeneous (clear cell) then the tumors were low-grade in 88.57 % of cases. Immunostaining heterogeneity was significant in the series and oscillated between 15 % for p110α and 80 % for Snail. When Snail immunostaining was homogeneous the tumor was histologically homogeneous in 100 % of cases. If Snail was heterogeneous, the tumor was heterogeneous in 75 % of the cases. Average tumor diameter was 4.3 cm. Tumors larger than 3.7 cm were heterogeneous for Vimentin immunostaining in 72.5 % of cases. Tumors displaying negative immunostaining for both ZEB1 and Twist were low grade in 100 % of the cases. Intratumor heterogeneity is a common event in clear cell renal cell carcinoma, which can be monitored by immunohistochemistry in routine practice. Snail seems to be particularly useful in the identification of intratumor heterogeneity. The suitability of current sampling protocols in renal cancer is discussed.

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

    PubMed

    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.

  6. Osteopontin traffic in hypoxic renal epithelial cells.

    PubMed

    Hampel, Dierk J; Sansome, Christine; Romanov, Victor I; Kowalski, Aaron J; Denhardt, David T; Goligorsky, Michael S

    2003-01-01

    Osteopontin (OPN), a secretory RGD-containing phosphoprotein, is induced in acute renal injury where it plays a renoprotective role. To investigate in depth the mode of OPN secretion under stress conditions, we analyzed OPN traffic in human renal proximal tubular epithelial cells (RPTEC). Western blot analysis and fluorescence microscopy revealed trace amounts of OPN in intact cells, whereas cytoplasmic OPN levels were significantly increased after 24-48 h hypoxia. Immunoelectron microscopy of RPTEC showed predominantly apical localization of gold-labeled OPN under normal conditions. Hypoxia (24 h) increased 2.5-fold immunodetectable gold-labeled OPN at the apical plasma membrane; further reoxygenation (2 h) augmented apical and basolateral labeling 2- and 10-fold, respectively. Analysis of apical and basolateral medium conditioned by RPTEC grown on semipermeable membranes using a specially developed ELISA showed a global decrease in secreted OPN after hypoxia, which recovered following 2 h reoxygenation. Agents known to disrupt the function of the Golgi apparatus (brefeldin A, monensin) or actin cytoskeleton (cytochalasin B) significantly inhibited OPN-GFP secretion in normoxic cells. In cells recovering from hypoxia, however, OPN secretion required functional Golgi apparatus, but was not affected by cytochalasin B. These findings demonstrate that stress inhibits OPN secretion by the process dependent on the functional Golgi apparatus and actin cytoskeleton; recovery restores OPN secretion, although its polarity may become perturbed. Copyright 2003 S. Karger AG, Basel

  7. Combination therapy for metastatic renal cell carcinoma

    PubMed Central

    Buonerba, Carlo; Di Lorenzo, Giuseppe

    2016-01-01

    Current therapy for metastatic clear cell renal cell carcinoma (RCC) consists of the serial administration of single agents. Combinations of VEGF and mTOR inhibitors have been disappointing in previous randomized trials. However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. Moreover, the emergence of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors has spawned the investigation of combinations of these agents with VEGF inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. These ongoing phase III trials in conjunction with the development of predictive biomarkers and agents inhibiting novel therapeutic targets may provide much needed advances in this still largely incurable disease. PMID:27047959

  8. Synchronized renal tubular cell death involves ferroptosis.

    PubMed

    Linkermann, Andreas; Skouta, Rachid; Himmerkus, Nina; Mulay, Shrikant R; Dewitz, Christin; De Zen, Federica; Prokai, Agnes; Zuchtriegel, Gabriele; Krombach, Fritz; Welz, Patrick-Simon; Weinlich, Ricardo; Vanden Berghe, Tom; Vandenabeele, Peter; Pasparakis, Manolis; Bleich, Markus; Weinberg, Joel M; Reichel, Christoph A; Bräsen, Jan Hinrich; Kunzendorf, Ulrich; Anders, Hans-Joachim; Stockwell, Brent R; Green, Douglas R; Krautwald, Stefan

    2014-11-25

    Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to be the pathophysiologically predominant pathway that leads to regulated necrosis of parenchymal cells in ischemia-reperfusion injury (IRI), and loss of either Fas-associated protein with death domain (FADD) or caspase-8 is known to sensitize tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury. In contrast, iron-dependent ferroptosis directly causes synchronized necrosis of renal tubules, as demonstrated by intravital microscopy in models of IRI and oxalate crystal-induced acute kidney injury. To suppress ferroptosis in vivo, we generated a novel third-generation ferrostatin (termed 16-86), which we demonstrate to be more stable, to metabolism and plasma, and more potent, compared with the first-in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily severe IRI, 16-86 exerts strong protection to an extent which has not previously allowed survival in any murine setting. In addition, 16-86 further potentiates the strong protective effect on IRI mediated by combination therapy with necrostatins and compounds that inhibit mitochondrial permeability transition. Renal tubules thus represent a tissue that is not sensitized to necroptosis by loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic renal necrosis, which may be therapeutically targeted by ferrostatins and by combination therapy.

  9. Renal cell cancer and exposure to gasoline: A review

    SciTech Connect

    McLaughlin, J.K.

    1993-12-01

    A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factors are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firm conclusion of no risk for this exposure. 48 refs.

  10. Renal allograft rejection: possible involvement of lymphokine-activated killer cells.

    PubMed Central

    Kirby, J A; Forsythe, J L; Proud, G; Taylor, R M

    1989-01-01

    Human renal allograft tissue was recovered at transplant nephrectomy from three patients with irreversible loss of graft function. This tissue was disaggregated and separated into two fractions on the basis of particle size. Fraction 1 contained glomeruli and developed a mixed outgrowth containing adherent epithelial and mesangial cells after a limited period of culture. Fraction 2 contained fragments of renal tubules and produced monolayers of tubular epithelial cells during culture. A population of lymphoid cells was observed to grow from the primary disaggregate into medium supplemented with recombinant human interleukin-2 (IL-2). After culture for 5 days these lymphoid cells were predominantly CD3-positive and carried both class II major histocompatibility antigens (MHC) and the CD25 IL-2 receptor. Culture of peripheral blood-derived mononuclear cells with IL-2 caused the generation of lymphokine-activated killer (LAK) cells; these cells were able to lyse both glomerular and tubular cells grown from nephrectomy tissue without showing MHC antigen restriction. The lymphoid cells grown from renal allograft tissue showed a similar lytic potential for both renal cells prepared from the same nephrectomy specimen and from third party renal tissue. It is possible that any LAK cells formed within a renal allograft by the action of IL-2 may contribute to the tissue destruction observed during graft rejection. Images Figure 2 PMID:2661417

  11. Contemporary Treatment of Metastatic Renal Cell Carcinoma

    PubMed Central

    Stukalin, Igor; Alimohamed, Nimira; Heng, Daniel Y.C.

    2016-01-01

    The introduction of targeted therapy has revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). The current standard of care focuses on the inhibition of angiogenesis through the targeting of the vascular endothelial growth factor receptor (VEGFR) and the mammalian target of rapamycin (mTOR). Over the past few years, research exploring novel targeted agents has blossomed, leading to the approval of various targeted therapies. Furthermore, results from the CheckMate025 and the METEOR trials have brought about two additional novel options: the programmed cell death 1 (PD-1) checkpoint inhibitor nivolumab and the MET/VEGFR/AXL inhibitor cabozantinib, respectively. With the variety of therapeutic agents available for treatment of mRCC, research examining appropriate sequencing and combinations of the drugs is ongoing. This review discusses the role of prognostic criteria, such as those from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. It also covers the current standard of treatment for mRCC with targeted therapy in first-, second-, and third-line setting. Additionally, the novel mechanism of action of nivolumab and cabozantinib, therapeutic sequencing and ongoing clinical trials are discussed. PMID:27471582

  12. B Cell Subsets Contribute to Both Renal Injury and Renal Protection after Ischemia/Reperfusion

    PubMed Central

    Renner, Brandon; Strassheim, Derek; Amura, Claudia R.; Kulik, Liudmila; Ljubanovic, Danica; Glogowska, Magdalena J.; Takahashi, Kazue; Carroll, Michael C.; Holers, V. Michael; Thurman, Joshua M.

    2011-01-01

    Ischemia/reperfusion (I/R) triggers a robust inflammatory response within the kidney. Numerous components of the immune system contribute to the resultant renal injury including the complement system. We sought to identify whether natural antibodies bind to the post-ischemic kidney and contribute to complement activation after I/R. We depleted peritoneal B cells in mice by hypotonic shock. Depletion of the peritoneal B cells prevented the deposition of IgM within the glomeruli after renal I/R, and attenuated renal injury after I/R. We found that glomerular IgM activates the classical pathway of complement but does not cause substantial deposition of C3 within the kidney. Furthermore, mice deficient in classical pathway proteins were not protected from injury, indicating that glomerular IgM does not cause injury through activation of the classical pathway. We also subjected mice deficient in all mature B cells (μMT mice) to renal I/R and found that they sustained worse renal injury than wild-type controls. Serum IL-10 levels were lower in the μMT mice. Regarded together, these results indicate that natural antibody produced by peritoneal B cells binds within the glomerulus after renal I/R and contributes to functional renal injury. However, non-peritoneal B cells attenuate renal injury after I/R, possibly through the production of IL-10. PMID:20810984

  13. Targeting HIF2 in Clear Cell Renal Cell Carcinoma.

    PubMed

    Cho, Hyejin; Kaelin, William G

    2016-12-08

    Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1. These compounds inhibit clear cell renal cell carcinoma growth in preclinical models, and PT2385 has now entered the clinic. Nonetheless, the availability of such compounds, together with clustered regularly interspaced short palindromic repeat (CRISPR)-based gene editing approaches, has revealed a previously unappreciated heterogeneity among clear cell renal carcinomas and patient-derived xenografts with respect to HIF2 dependence, suggesting that predictive biomarkers will be needed to optimize the use of such agents in the clinic.

  14. Mesenchymal stem cells derived from adipose tissue are not affected by renal disease.

    PubMed

    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.

  15. Malignancies in a renal transplant population: The St. Michael's Hospital experience

    PubMed Central

    Saleeb, R.; Faragalla, H.; Yousef, G. M.; Stewart, R.; Streutker, C. J.

    2016-01-01

    Introduction: Previous publications have shown an increased incidence of various malignancies amongst renal transplant populations. The objective of this study was to analyze the rate and types of malignancies occurring in the St. Michael's Hospital renal transplant population and to determine whether our results were comparable to those previously published. Methods: After approval by the hospital's research ethic board, review of the records and pathology of the 1584 patients in the renal transplant clinic database patients was performed. The reports dated back to the year 1970. Results: Amongst the 1584 renal transplant patients, 106 patients with 132 dysplastic and malignant posttransplant lesions were identified. The highest incidence amid the malignancies was in nonmelanoma skin malignancies squamous cell carcinoma (SCC), basal cell carcinoma, and Kaposi sarcoma, with a total of 32 patients having 54 separate tumors (2.02% of all patients, 43.2% of tumors). Following skin tumors in incidence were genitourinary (28 tumors), gastrointestinal tract (GIT) lesions (8 adenocarcinomas, 14 dysplastic lesions, 1 low grade neuroendocrine tumor/carcinoid), posttransplant lymphoproliferative disorders (PTLDs) (10 cases), gynecologic (6 carcinomas), cervical/anal/vulvar dysplasia and invasive (SCCs) (4), and thyroid (3 papillary tumors). Nine patients had tumors of multiple sites/types. With respect to outcome, 14 patients died of malignancy, with the highest mortality being in the GIT malignancies (six patients). Second in mortality were the PTLD and skin tumor groups. Discussion: Information on the incidence and outcome of various malignancies in renal transplant patients is important in designing guidelines for the follow-up of these patients regarding tumor screening and prevention. The rate of malignancies in our group is comparable to that reported in other centers. PMID:27141185

  16. Contribution of apoptotic cell death to renal injury.

    PubMed

    Ortiz, A; Lorz, C; Justo, P; Catalán, M P; Egido, J

    2001-01-01

    Cell number abnormalities are frequent in renal diseases, and range from the hypercellularity of postinfectious glomerulonephritis to the cell depletion of chronic renal atrophy. Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in the kidney. The role of apoptosis ranges from induction to repair and progression of renal injury. Death ligands and receptors, such as TNF and FasL, proapoptotic and antiapoptotic Bcl-2 family members and caspases have all been shown to participate in apoptosis regulation in the course of renal injury. These proteins represent potential therapeutic targets, which should be further explored.

  17. Usefulness of CT During Renal Arteriography: A Case of Percutaneous Radiofrequency Ablation for Renal Cell Carcinoma

    SciTech Connect

    Tanigawa, Noboru Kariya, Shuji; Komemushi, Atsushi; Kojima, Hiroyuki; Sawada, Satoshi

    2004-11-15

    A 64-year-old man with a unilateral 15 mm diameter renal cell carcinoma underwent percutaneous radiofrequency ablation (RFA) assisted by CT during renal arteriography (angio-CT). Prior to placement of the needle electrode, a 5 Fr angio-catheter was placed in the right renal artery, and angio-CT was performed before, during and after the procedure. Since multiple angio-CT can be performed using a small amount of diluted contrast agent, RFA can be monitored without impairing renal function. As a result, this imaging combination was found to be useful for determining the end point of ablation.

  18. Enhanced propagation of adult human renal epithelial progenitor cells to improve cell sourcing for tissue-engineered therapeutic devices for renal diseases.

    PubMed

    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.

  19. Wnt Signaling in Renal Cell Carcinoma

    PubMed Central

    Xu, Qi; Krause, Mirja; Samoylenko, Anatoly; Vainio, Seppo

    2016-01-01

    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. PMID:27322325

  20. The association between chronic renal failure and renal cell carcinoma may differ between black and white Americans

    PubMed Central

    Hofmann, Jonathan N; Schwartz, Kendra; Chow, Wong-Ho; Ruterbusch, Julie J; Shuch, Brian M; Karami, Sara; Rothman, Nathaniel; Wacholder, Sholom; Graubard, Barry I; Colt, Joanne S; Purdue, Mark P

    2012-01-01

    Purpose In the United States, renal cell carcinoma (RCC) incidence is higher among blacks than among whites. Risk of RCC is elevated among end-stage renal disease patients, although no studies have looked at differences by race in the relationship between chronic renal failure and RCC. Methods We investigated RCC risk in relation to chronic renal failure in a population-based case-control study of blacks and whites in Chicago and Detroit. Data, including information on kidney disease, were collected from interviews with 1,217 RCC cases (361 blacks, 856 whites) and 1,235 controls (523 blacks, 712 whites). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. Results Risk of RCC was increased in relation to chronic renal failure (OR 4.7, 95% CI 2.2–10.1) and dialysis (OR 18.0, 95% CI 3.6–91). The association remained after defining exposure as those who had chronic renal failure ≥10 years prior to RCC diagnosis. Chronic renal failure was more strongly associated with RCC among blacks than among whites (OR 8.7, 95% CI 3.3–22.9 and 2.0, 0.7–5.6 respectively; Pinteraction=0.03) and among those without a history of diabetes relative to diabetic subjects (OR 8.3, 95% CI 3.1–22.7 and 1.9, 0.6–5.9 respectively; Pinteraction=0.03). Conclusions These results suggest that chronic renal failure is a strong risk factor for RCC, particularly among black and non-diabetic subjects. Our findings of differences in risk estimates by race, to our knowledge the first such report, require replication. PMID:23179659

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

    PubMed

    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.

  2. A Case of Hereditary Leiomyomatosis and Renal Cell Carcinoma

    PubMed Central

    Mehrtens, Sarah; Veitch, David; Kulakov, Elizabeth; Perrett, Conal M.

    2016-01-01

    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. PMID:27144040

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

    PubMed

    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.

  4. Renal Cell Carcinomas: Sonographic Appearance Depending on Size and Histologic Type.

    PubMed

    Sidhar, Kunal; McGahan, John P; Early, Heather M; Corwin, Michael; Fananapazir, Ghaneh; Gerscovich, Eugenio O

    2016-02-01

    Prior studies have demonstrated that approximately 10% of malignant renal cell carcinomas are as echogenic as angiomyolipomas on sonography. However, a recent presentation suggested that small (<1-cm) echogenic renal masses are always angiomyolipomas or other benign entities. We therefore examined our own cases of renal cell carcinoma, with corresponding sonography, to confirm that some renal cell carcinomas may also be detected as hyperechoic masses on sonography. Institutional Review Board approval and Health Insurance Portability and Accountability Act compliance were maintained for this retrospective review of 91 pathologically proven cases of renal cell carcinoma, with corresponding sonography. Tumors were first differentiated by histologic cell type (clear cell, papillary, and chromophobe). Tumors were then stratified according to 2 size group parameters, falling into those that were 3 cm or larger and those that were smaller than 3 cm in diameter, with the less than 3-cm group further subdivided into 2 cm or smaller and greater than 2 cm. Tumor echogenicity was graded on a 5-point scale with respect to the renal parenchyma. Forty-six tumors (51%) were 3 cm in diameter or smaller, and most were found to be either isoechoic (35%) or mildly hyperechoic (26%) to the surrounding renal parenchyma. Of tumors smaller than 2 cm, most were either mildly hyperechoic (29%) or as hyperechoic as renal sinus fat (very hyperechoic; 29%). Tumors larger than 3 cm were found most often to be either isoechoic (49%) or mildly hyperechoic (33%), with only 4% found to be very hyperechoic. The sonographic appearances of renal cell carcinomas include a small population that are very hyperechoic on sonography and thus could potentially be misdiagnosed as angiomyolipomas. © 2016 by the American Institute of Ultrasound in Medicine.

  5. Quiz. Correct answer to the quiz. Check your diagnosis. Clear cell papillary renal cell carcinoma.

    PubMed

    Joseph, Keva; Liu, Kai-Wen; Chang, I-Wei

    2015-06-01

    We incidentally observed a case of clear cell papillary renal cell carcinoma of an 81-year-old woman, presenting with intermittent left flank pain. It is a recently described rare renal parenchymal tumor.

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

    PubMed

    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.

  7. Bioartificial Renal Epithelial Cell System (BRECS): A Compact, Cryopreservable Extracorporeal Renal Replacement Device

    PubMed Central

    Buffington, Deborah A.; Pino, Christopher J.; Chen, Lijun; Westover, Angela J.; Hageman, Gretchen; Humes, H. David

    2012-01-01

    Renal cell therapy has shown clinical efficacy in the treatment of acute renal failure (ARF) and promise for treatment of end-stage renal disease (ESRD) by supplementing conventional small solute clearance (hemodialysis or hemofiltration) with endocrine and metabolic function provided by cells maintained in an extracorporeal circuit. A major obstacle in the widespread adoption of this therapeutic approach is the lack of a cryopreservable system to enable distribution, storage, and therapeutic use at point of care facilities. This report details the design, fabrication, and assessment of a Bioartificial Renal Epithelial Cell System (BRECS), the first all-in-one culture vessel, cryostorage device, and cell therapy delivery system. The BRECS was loaded with up to 20 cell-seeded porous disks, which were maintained by perfusion culture. Once cells reached over 5×106 cells/disk for a total therapeutic dose of approximately 108 cells, the BRECS was cryopreserved for storage at −80°C or −140°C. The BRECS was rapidly thawed, and perfusion culture was resumed. Near precryopreservation values of cell viability, metabolic activity, and differentiated phenotype of functional renal cells were confirmed postreconstitution. This technology could be extended to administer other cell-based therapies where metabolic, regulatory, or secretion functions can be leveraged in an immunoisolated extracorporeal circuit. PMID:24575327

  8. Hereditary leiomyomatosis and renal cell cancer (HLRCC). Renal cancer risk, surveillance and treatment

    PubMed Central

    Menko, Fred H.; Maher, Eamonn; Schmidt, Laura S.; Middelton, Lindsay A.; Aittomäki, Kristiina; Tomlinson, Ian; Richard, Stéphane; Linehan, W. Marston

    2015-01-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition in which susceptible individuals are at risk for the development of cutaneous leiomyomas, early onset multiple uterine leiomyomas and an aggressive form of type 2 papillary renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene, which inactivates the enzyme and alters the function of the tricarboxylic acid (TCA/ Krebs) cycle. Issues surrounding surveillance and treatment for HLRCC-associated renal cell cancer were considered as part of a recent international symposium on HLRCC. The management protocol proposed in this article is based on a literature review and a consensus meeting. The estimated lifetime renal cancer risk for FH mutation carriers is estimated to be 15%. In view of the potential for early onset of RCC in HLRCC, periodic renal imaging and, when available, predictive testing for a FH mutation is recommended from 8 to 10 years of age. However, the small risk of renal cell cancer in the 10-20 years age range and the potential drawbacks of screening should be carefully discussed on an individual basis. Surveillance preferably consists of annual abdominal MRI. Treatment of renal tumours should be prompt and generally consist of wide-margin surgical excision and consideration of retroperitoneal lymph node dissection. The choice for systemic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts of families. PMID:25012257

  9. An in vitro model of renal proximal tubule cell regeneration.

    PubMed

    Kays, S E; Berdanier, C D; Swagler, A R; Lock, E A; Schnellmann, R G

    1993-08-01

    The ability of renal cells to regenerate is critical for the recovery of renal function following injury. Research on the recovery of renal function has been limited by the lack of in vitro models of renal repair. The goal of this study was to develop an in vitro model of renal proximal tubule cell (RPTC) injury and regeneration using primary cultures of rabbit RPTC. Renal proximal tubules were isolated and cultured in hormonally defined DME/F-12 medium at 37 degrees C under 95% air/5% CO2. RPTC were grown to confluency, made quiescent by the removal of insulin and hydrocortisone from the medium for 24-48 hr, and treated with the nephrotoxicant, 1,2-dichlorovinyl-L-cysteine (DCVC). DCVC (100 microM for 2 hr, n = 3-6) resulted in cell injury and the release of nonviable cells from the plate at 24 hr (55% +/- 6% confluency, mean +/- SEM) and 48 hr (37% +/- 7% confluency). Cell monolayers began to regenerate 96 hr after exposure (57% +/- 9% confluency) and continued to regenerate reaching 76% +/- 8% and 84% +/- 1% confluency by 6 and 8 days postexposure. Control cells maintained confluency throughout the experiment. Thus, an in vitro primary cell culture model has been developed in which the cell monolayer regenerates after nephrotoxicant-induced injury. This model may be useful in the study of mechanisms of renal cell injury and repair.

  10. Kidney dendritic cells in acute and chronic renal disease.

    PubMed

    Hochheiser, Katharina; Tittel, André; Kurts, Christian

    2011-06-01

    Dendritic cells are not only the master regulators of adaptive immunity, but also participate profoundly in innate immune responses. Much has been learned about their basic immunological functions and their roles in various diseases. Comparatively little is still known about their role in renal disease, despite their obvious potential to affect immune responses in the kidney, and immune responses that are directed against renal components. Kidney dendritic cells form an abundant network in the renal tubulointerstitium and constantly survey the environment for signs of injury or infection, in order to alert the immune system to the need to initiate defensive action. Recent studies have identified a role for dendritic cells in several murine models of acute renal injury and chronic nephritis. Here we summarize the current knowledge on the role of kidney dendritic cells that has been obtained from the study of murine models of renal disease. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

  11. Metabolic alterations in renal cell carcinoma.

    PubMed

    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.

  12. Sequential Therapy in Metastatic Renal Cell Carcinoma

    PubMed Central

    Burke, John M.; Agrawal, Manish; Hauke, Ralph J.; Hutson, Thomas E.; Doshi, Gury; Fleming, Mark T.; Vogelzang, Nicholas J.

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network’s Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future. PMID:28326277

  13. Sunitinib resistance in renal cell carcinoma

    PubMed Central

    2014-01-01

    Of the many targeted therapies introduced since 2006, sunitinib has carved its way to become the most commonly used first-line therapy for the treatment of metastatic renal cell carcinoma (RCC). Despite significant improvements in progression-free survival, 30% of the patients are intrinsically resistant to sunitinib and the remaining 70% who respond initially will eventually become resistant in 6–15 months. While the molecular mechanisms of acquired resistance to sunitinib have been unravelling at a rapid rate, the mechanisms of intrinsic resistance remain elusive. Combination therapy, sunitinib rechallenge and sequential therapy have been investigated as means to overcome resistance to sunitinib. Of these, sequential therapy appears to be the most promising strategy. This mini review summarises our emerging understanding of the molecular mechanisms, and the strategies employed to overcome sunitinib resistance.

  14. Computed tomography in metastatic renal cell carcinoma.

    PubMed

    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.

  15. Unilateral Blepharoptosis from Renal Cell Carcinoma

    PubMed Central

    Sabatino, Lorenzo; Sabatino, Francesco; Casale, Manuele; Quattrocchi, Carlo Cosimo; Zobel, Bruno Beomonte

    2016-01-01

    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. PMID:28326282

  16. Renal Cell Carcinoma Metastatic to the Scalp

    PubMed Central

    Errami, Mounir; Margulis, Vitali; Huerta, Sergio

    2016-01-01

    Because of the asymptomatic natural history of renal cell carcinoma (RCC), by the time a diagnosis is made, metastatic disease is present in about one third of the cases. Thus, the overall survival of patients with RCC remains poor. Ultimately up to 50% of patients with RCC will develop metastases. Metastatic lesions from RCC are usually observed in the lungs, liver or bone. Metastases to the brain or the skin from RCC are rare. Here we present a patient diagnosed with RCC, found to have no evidence of metastases at the time of nephrectomy, who presented two years later with metastases to the scalp. We review the literature of patients with this rare site of metastasis and outline the overall prognosis of this lesion compared to other site of metastases from RCC. PMID:28191289

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

    PubMed

    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

  18. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    PubMed Central

    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

  19. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    PubMed

    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 H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; 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; 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, Harsha V; Drummond, Jennifer A; 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, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various 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, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  20. Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering.

    PubMed

    Batchelder, Cynthia A; Martinez, Michele L; Tarantal, Alice F

    2015-01-01

    Despite the enthusiasm for bioengineering of functional renal tissues for transplantation, many obstacles remain before the potential of this technology can be realized in a clinical setting. Viable tissue engineering strategies for the kidney require identification of the necessary cell populations, efficient scaffolds, and the 3D culture conditions to develop and support the unique architecture and physiological function of this vital organ. Our studies have previously demonstrated that decellularized sections of rhesus monkey kidneys of all age groups provide a natural extracellular matrix (ECM) with sufficient structural properties with spatial and organizational influences on human embryonic stem cell (hESC) migration and differentiation. To further explore the use of decellularized natural kidney scaffolds for renal tissue engineering, pluripotent hESC were seeded in whole- or on sections of kidney ECM and cell migration and phenotype compared with the established differentiation assays for hESC. Results of qPCR and immunohistochemical analyses demonstrated upregulation of renal lineage markers when hESC were cultured in decellularized scaffolds without cytokine or growth factor stimulation, suggesting a role for the ECM in directing renal lineage differentiation. hESC were also differentiated with growth factors and compared when seeded on renal ECM or a new biologically inert polysaccharide scaffold for further maturation. Renal lineage markers were progressively upregulated over time on both scaffolds and hESC were shown to express signature genes of renal progenitor, proximal tubule, endothelial, and collecting duct populations. These findings suggest that natural scaffolds enhance expression of renal lineage markers particularly when compared to embryoid body culture. The results of these studies show the capabilities of a novel polysaccharide scaffold to aid in defining a protocol for renal progenitor differentiation from hESC, and advance the promise

  1. Chronic kidney disease and risk of renal cell carcinoma: differences by race

    PubMed Central

    Hofmann, Jonathan N.; Corley, Douglas A.; Zhao, Wei K.; Colt, Joanne S.; Shuch, Brian; Chow, Wong-Ho; Purdue, Mark P.

    2015-01-01

    Background The incidence of renal cell carcinoma in the United States differs by race/ethnicity. To better understand these disparities, we conducted a nested case-control study investigating renal cell carcinoma risk factors across racial/ethnic groups within the Kaiser Permanente Northern California health care network. Methods Our study included 3,136 renal cell carcinoma cases (2,152 white, 293 black, 425 Hispanic, 255 Asian) diagnosed between 1998 and 2008 and 31,031 individually matched controls (21,478 white, 2,836 black, 4,147 Hispanic, 2,484 Asian). Risk of renal cell carcinoma was assessed in relation to smoking status, body mass index (BMI), hypertension, and chronic kidney disease. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, and population attributable risk (PAR) to estimate by race the proportion of cases attributable to hypertension and chronic kidney disease. Results The association between chronic kidney disease and renal cell carcinoma differed markedly by race (Pinteraction<0.001), with associations observed among blacks (OR=10.4 [95% CI=6.0–17.9]), Asians (5.1 [2.2–11.7]), and Hispanics (2.3 [1.1–4.6]) but not whites (1.1 [0.6–1.9]). Hypertension, high BMI, and smoking were associated with renal cell carcinoma, but findings generally did not differ by race. Relative to other racial/ethnic groups, blacks had the highest proportion of renal cell carcinoma incidence attributable to hypertension and chronic kidney disease (combined, PAR=37%; hypertension only, PAR=27%; chronic kidney disease, PAR=10%). Conclusions Our findings suggest that hypertension and chronic kidney disease likely have contributed to the observed excess in renal cell carcinoma incidence among blacks compared with whites. PMID:25393631

  2. Mortality in the Veneto population on renal replacement therapy.

    PubMed

    Nordio, Maurizio; Tessitore, Nicola; Feriani, Mariano; Rossi, Barbara; Virga, Giovambattista; Amici, Giampaolo; Abaterusso, Cataldo; Antonucci, Francesco

    2013-01-01

    This section reports survival rates for patients on renal replacement therapy (RRT). The data obtained from the Veneto Dialysis and Transplantation Registry (VDTR) cover the whole population in the region. Patients on RRT alive on 31 December of each year were assumed to be at risk of dying in the following year. Furthermore, time-to-event analysis was used to describe the complete history of patients from when they started RRT until they died, including transitions between the 3 main treatment modalities - hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation. The cohort of patients starting RRT from 1998 to 2010 was followed up until 31 December 2010. Survival rates from the first treatment to death were calculated according to the life table method. Relative survival and excess mortality rates were estimated according to the Ederer II method. A multistate model was used to describe changes in a patient's condition (changes of treatment, or death) over time. Among prevalent patients on RRT, the annual risk of death was 10.65% in 2008, 9.35% in 2009 and 8.86% in 2010. The overall mortality rate was 12.5 per 100 patient-years (95% confidence interval [95% CI], 12.1-13.0). The 5-year relative survival was 59% (95% CI, 57%-60%), and at 10 years relative survival was 41% (95% CI, 39%-43%); the estimated excess mortality rate was very high at the start of RRT (18 per 100 patient-years) but gradually decreased after the second year. On multivariate analysis, excess mortality was associated with age and primary renal diseases. Less than 10% of patients starting on PD shifted to HD in the first year of RRT, and a considerable proportion received a transplant, amounting to 6% in the first year, and thereafter increasing steadily: at the end of the fifth year, 34% of patients starting RRT on PD had received a transplant. HD patients behaved differently: any shift to PD was negligible, and the patients receiving a transplant amounted to only 2% in the first

  3. Heparanase expression and glycosaminoglycans profile in renal cell carcinoma.

    PubMed

    Batista, Lucas Teixeira E Aguiar; Matos, Leandro Luongo; Machado, Leopoldo Ruiz; Suarez, Eloah Rabello; Theodoro, Thérèse Rachell; Martins, João Roberto Maciel; Nader, Helena Bonciani; Pompeo, Antonio Carlos Lima; Pinhal, Maria Aparecida da Silva

    2012-11-01

    A better understanding of the molecular mechanisms of renal cell carcinogenesis could contribute to a decrease in the mortality rate of this disease. The aim of this study was to evaluate the glycosaminoglycans profile and heparanase expression in renal cell carcinoma. The study included 24 patients submitted to nephrectomy with confirmed pathological diagnosis of renal cell carcinoma. The majority of the samples (87.5%) were classified in the initial stage of renal cell carcinoma (clinical stages I and II). Heparanase messenger ribonucleic acid expression was evaluated by quantitative real-time reverse transcription polymerase chain reaction, and sulfated glycosaminoglycans were identified and quantified by agarose gel electrophoresis of renal cell carcinoma samples or non-neoplastic tissues obtained from the same patients (control group). The sulfated glycosaminoglycans and hyaluronic acid were analyzed in urine samples of the patients before and after surgery. The data showed a significant statistical increase in chondroitin sulfate, and a decrease in heparan sulfate and dermatan sulfate present in neoplastic tissues compared with non-neoplastic tissues. Higher heparanase messenger ribonucleic acid expression in the neoplastic tissues was also shown, compared with the non-neoplastic tissues. The urine glycosaminoglycans profile showed no significant difference between renal cell carcinoma and control samples. Extracellular matrix changes observed in the present study clarify that heparanase is possibly involved with heparan sulfate turnover, and that heparanase and the glycosaminoglycans can modulate initial events of renal cell carcinoma development.

  4. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  5. [Synchronous bilateral chromophobe cell renal carcinoma: a case report].

    PubMed

    Mukai, Masatoshi; Imamura, Ryoichi; Takayama, Hitoshi; Nishimura, Kazuo; Nonomura, Norio; Okuyama, Akihiko

    2009-09-01

    An 81-year-old female presented with abdominal discomfort. Computed tomography scan showed a 26 x 22 mm tumor in the left kidney and 43 x 37 mm tumor in the right kidney. Clinical diagnosis was bilateral renal cell carcinoma, left; cT1a, right; cT1bN0M0. We planned primary unilateral partial nephrectomy, followed by secondary contralateral radical nephrectomy. Left partial nephrectomy was performed and 4 months later, laparoscopic right renal nephrectomy was performed without serious postoperative renal dysfunction. Pathological diagnosis of both tumors was chromophobe renal carcinoma. The patient has been doing well without any evidence of recurrence or metastasis.

  6. Expression of adrenergic and cholinergic receptors in murine renal intercalated cells.

    PubMed

    Jun, Jin-Gon; Maeda, Seishi; Kuwahara-Otani, Sachi; Tanaka, Koichi; Hayakawa, Tetsu; Seki, Makoto

    2014-11-01

    Neurons influence renal function and help to regulate fluid homeostasis, blood pressure and ion excretion. Intercalated cells (ICCs) are distributed throughout the renal collecting ducts and help regulate acid/base equilibration. Because ICCs are located among principal cells, it has been difficult to determine the effects that efferent nerve fibers have on this cell population. In this study, we examined the expression of neurotransmitter receptors on the murine renal epithelial M-1 cell line. We found that M-1 cells express a2 and b2 adrenergic receptor mRNA and the b2 receptor protein. Further, b2 receptor-positive cells in the murine cortical collecting ducts also express AQP6, indicating that these cells are ICCs. M-1 cells were found to express m1, m4 and m5 muscarinic receptor mRNAs and the m1 receptor protein. Cells in the collecting ducts also express the m1 receptor protein, and some m1-positive cells express AQP6. Acetylcholinesterase was detected in cortical collecting duct cells. Interestingly, acetylcholinesterase-positive cells neighbored AQP6-positive cells, suggesting that principal cells may regulate the availability of acetylcholine. In conclusion, our data suggest that ICCs in murine renal collecting ducts may be regulated by the adrenergic and cholinergic systems.

  7. Expression of Adrenergic and Cholinergic Receptors in Murine Renal Intercalated Cells

    PubMed Central

    JUN, Jin-Gon; MAEDA, Seishi; KUWAHARA-OTANI, Sachi; TANAKA, Koichi; HAYAKAWA, Tetsu; SEKI, Makoto

    2014-01-01

    ABSTRACT Neurons influence renal function and help to regulate fluid homeostasis, blood pressure and ion excretion. Intercalated cells (ICCs) are distributed throughout the renal collecting ducts and help regulate acid/base equilibration. Because ICCs are located among principal cells, it has been difficult to determine the effects that efferent nerve fibers have on this cell population. In this study, we examined the expression of neurotransmitter receptors on the murine renal epithelial M-1 cell line. We found that M-1 cells express a2 and b2 adrenergic receptor mRNA and the b2 receptor protein. Further, b2 receptor-positive cells in the murine cortical collecting ducts also express AQP6, indicating that these cells are ICCs. M-1 cells were found to express m1, m4 and m5 muscarinic receptor mRNAs and the m1 receptor protein. Cells in the collecting ducts also express the m1 receptor protein, and some m1-positive cells express AQP6. Acetylcholinesterase was detected in cortical collecting duct cells. Interestingly, acetylcholinesterase-positive cells neighbored AQP6-positive cells, suggesting that principal cells may regulate the availability of acetylcholine. In conclusion, our data suggest that ICCs in murine renal collecting ducts may be regulated by the adrenergic and cholinergic systems. PMID:25069412

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

    PubMed

    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.

  9. A patient with Multiple myeloma and Renal cell carcinoma

    PubMed Central

    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. PMID:27047652

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

    PubMed

    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.

  11. Axitinib in metastatic renal cell carcinoma: single center experience

    PubMed Central

    Kardas, Joanna

    2017-01-01

    Aim of the study Due to the emergence of new therapeutic opportunities in the second-line treatment of metastatic renal cell carcinoma, the choice of the appropriate medication requires consideration. Making the selection one should take into account the likelihood of response, the probability of toxicity, properties of the drug and the clinical characteristics of the patient. Aim of the work was to confirm antitumor efficacy of axitinib in patients with metastatic clear-cell renal-cell carcinoma in the second line treatment remaining under the care of our institution. The primary objective was to determine antitumor activity, secondary – to evaluate progression free survival, safety of the treatment and to analyse clinical characteristics of treated population. Results Treatment records of 27 patients (9 females, 18 males) treated from October 2014 to the present (July 2016) were reviewed. The median duration of treatment which corresponds to the time to disease progression in observed population was 6 months (range: under 1 month – 16 months). 1 patient (3.7%) had got objective response (PR, partial remission). Clinical benefit rate (PR + SD (stable disease) was 66%. 9 patients (33.33%) experienced treatment toxicity only in the first degree of CTCAE (common toxicity criteria for adverse events), 11 patients (40.74%) presented the second degree toxicity and 5 patients (18.5%) – third degree. The most commonly reported treatment related adverse events were diarrhea (47%), fatigue (26%), hand-foot syndrome (26%), deterioration of blood pressure control (22.2%), abnormal liver function tests (18.5%), mucositis (11.1%). We observed 3 cases of unacceptable toxicity. Conclusions Axitinib confirms its effectiveness also in situation outside clinical trials, however, it is characterized by significant toxicity. Therefore, qualification for treatment should take into account the clinical patient characteristics. Effective diagnosis and treatment of side effects and

  12. Plasmablastic multiple myeloma following clear cell renal cell carcinoma

    PubMed Central

    Padhi, Somanath; Mokkappan, Sudhagar; Varghese, Renu G’ Boy; Veerappan, Ilangovan

    2014-01-01

    We aim to describe the clinicohaematological profile of an elderly male with plasmablastic multiple myeloma (MM) (IgG λ, International System Stage II) with an unfavourable outcome following chemotherapy. The serum interleukin-6 level was found to be markedly elevated (2464 pg/mL, reference; <50 pg/mL). Thirty-six months prior to MM diagnosis, he underwent left radical nephrectomy for a stage III (pT3N0M0) clear cell renal cell carcinoma (RCC, Fuhrman grade 2). The unique MM-RCC association, shared risk factors, myeloma pathobiology and clinical implications are discussed with a brief literature review. PMID:25103318

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  16. Transitional cell cancer of the urinary tract and renal cell cancer in relation to acetaminophen use (United States).

    PubMed

    Rosenberg, L; Rao, R S; Palmer, J R; Strom, B L; Zauber, A; Warshauer, M E; Stolley, P D; Shapiro, S

    1998-01-01

    Experimental and epidemiologic evidence have suggested that phenacetin use increases the risk of transitional cell cancers of the urinary tract. The drug is no longer marketed but a commonly used metabolite, acetaminophen, has been linked recently to an increased risk of renal cancer. We assessed the relation of acetaminophen use to the risk of transitional cell cancer of the urinary tract and of renal cell cancer with data from a hospital-based study of cancers and medication use conducted from 1976-96 in the eastern United States. We compared 498 cases of transitional cell cancer and 383 cases of renal cell cancer with 8,149 noncancer controls and 6,499 cancer controls and controlled confounding factors with logistic regression. For transitional cell cancer, the relative risk (RR) estimate for regular acetaminophen use that had begun at least a year before admission was 1.1 (95 percent confidence interval [CI] = 0.6-1.9) based on noncancer controls, and 0.9 (CI = 0.5-1.6) based on cancer controls. RR estimates for use that lasted at least five years, and for nonregular use, were also close to 1.0. For renal cell cancer, the corresponding estimates were again close to 1.0. Our results suggest that acetaminophen, as used in present study population, does not influence the risk of transitional cell cancer of the urinary tract or of renal cell cancer.

  17. Reduced expression of CXCR4, a novel renal cancer stem cell marker, is associated with high-grade renal cell carcinoma.

    PubMed

    Rasti, Arezoo; Abolhasani, Maryam; Zanjani, Leili Saeednejad; Asgari, Mojgan; Mehrazma, Mitra; Madjd, Zahra

    2017-01-01

    Cancer stem cells (CSCs) represent a population with tumour-initiating, self-renewal, and differentiation potential. This study aimed to evaluate the expression patterns and clinical significance of chemokine receptor type 4 (CXCR4) as a novel CSC marker in renal cell carcinoma (RCC). The expression of CXCR4 was examined in 173 well-defined renal tumour tissues, including 106 (61.5 %) clear cell renal cell carcinomas (ccRCCs), 35 (20 %) papillary renal cell carcinomas (pRCCs), and 32 (18.5 %) chromophobe renal cell carcinomas (ChRCCs), by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters was then analysed. There was a significant difference in the expression levels of CXCR4 in the ccRCC samples compared to the ChRCC and pRCC samples (P < 0.001). Increased expression of CXCR4 was significantly correlated with higher-grade tumours (P < 0.001) and worse stage (P = 0.001). A significant association was also found between expression of CXCR4 and microvascular invasion (P = 0.018). Among RCC subtypes, comparison of the differences between CXCR4 expression in low- and high-grade tumours demonstrated that pRCC tumours had a significantly higher expression of CXCR4 (P < 0.001) than ccRCC tumours (P = 0.01). Significantly higher expression levels of CXCR4 were found in pRCC and ccRCC samples. Increased CXCR4 expression was associated with more aggressive tumour behaviour in RCC patients, especially in pRCC and ccRCC subtypes due to their more metastatic behaviour. These findings suggest that CXCR4 can be considered as a novel diagnostic and therapeutic marker for targeted therapy of renal carcinoma.

  18. Clear Cell Papillary Renal Cell Carcinoma and Renal Angiomyoadenomatous Tumor – Two Variants of a Morphologic, Immunohistochemical and Genetic Distinct Entity of Renal Cell Carcinoma

    PubMed Central

    Deml, Karl-Friedrich; Schildhaus, Hans-Ulrich; Compérat, Eva; von Teichman, Adriana; Storz, Martina; Schraml, Peter; Bonventre, Joseph V.; Fend, Falko; Fleige, Barbara; Nerlich, Andreas; Gabbert, Helmut Erich; Gaβler, Nikolaus; Grobholz, Rainer; Hailemariam, Seife; Hinze, Raoul; Knüchel, Ruth; Lhermitte, Benoit; Nesi, Gabriella; Rüdiger, Thomas; Sauter, Guido; Moch, Holger

    2015-01-01

    Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary renal cell carcinoma (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT. We investigated 28 ccpRCC and 9 RAT samples by immunohistochemistry using 25 markers. VHL gene mutations and allele losses were investigated by Sanger sequencing and fluorescence in situ hybridization (FISH). Clinical follow-up data were obtained for a subset of the patients. No tumor recurrence or tumor-related death was observed in any of the patients. Immunohistochemistry and molecular analyses led to the reclassification of three tumors as ccRCC and TFE3 translocation carcinomas. The immunohistochemical profile of ccpRCC and RAT samples was very similar but not identical, differing from both ccRCC and pRCC. Especially, the parafibromin and hKIM-1 expression exhibited differences in ccpRCC/RAT compared with ccRCC and pRCC. Genetic analysis revealed VHL mutations in 2/27 (7%) and 1/7 (14%) ccpRCC and RAT samples, respectively. FISH analysis disclosed a 3p loss in 2/20 (10 %) ccpRCC samples. ccpRCC and RAT have a specific morphologic and immunohistochemical profile but they share similarities with the more aggressive renal tumors. Based on our results, we regard ccpRCC/RAT as a distinct entity of renal cell carcinomas. PMID:25970683

  19. Understanding Papillary Renal Cell Carcinoma | Center for Cancer Research

    Cancer.gov

    Renal cell carcinoma (RCC), the most common form of kidney cancer in adults, is not a single disease but rather a collection of different tumor types driven by distinct genetic changes that arise within the same tissue.

  20. Recent advances in the management of renal cell carcinoma

    PubMed Central

    Molina, Ana M.; Nanus, David M.

    2016-01-01

    Therapeutic options for patients with metastatic renal cell carcinoma have significantly improved over the past few years with the recent approval of two new agents resulting in prolonged progression-free and overall survival. PMID:27019698

  1. Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non-sarcomatoid renal carcinomas.

    PubMed

    Sircar, Kanishka; Yoo, Suk-Young; Majewski, Tadeusz; Wani, Khalida; Patel, Lalit R; Voicu, Horatiu; Torres-Garcia, Wandaliz; Verhaak, Roel G W; Tannir, Nizar; Karam, Jose A; Jonasch, Eric; Wood, Christopher G; Tamboli, Pheroze; Baggerly, Keith A; Aldape, Kenneth D; Czerniak, Bogdan

    2015-10-01

    Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non-sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non-sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA-seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non-sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high-grade, high-stage non-sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial-to-mesenchymal transition signature. Our genome-scale microarray-based transcript data were validated in an independent set of sarcomatoid and non-sarcomatoid clear cell renal cell carcinomas using RNA-seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non-sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology augurs a poor prognosis; suggest the

  2. Biphasic components of sarcomatoid clear cell renal cell carcinomas are molecularly similar to each other, but distinct from, non‐sarcomatoid renal carcinomas

    PubMed Central

    Sircar, Kanishka; Yoo, Suk‐Young; Majewski, Tadeusz; Wani, Khalida; Patel, Lalit R.; Voicu, Horatiu; Torres‐Garcia, Wandaliz; Verhaak, Roel G. W.; Tannir, Nizar; Karam, Jose A.; Jonasch, Eric; Wood, Christopher G.; Tamboli, Pheroze; Baggerly, Keith A.

    2015-01-01

    Abstract Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear cell renal cell carcinoma. Our understanding of sarcomatoid change has been hindered by the lack of molecular examination. Thus, we sought to characterize molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma and compare them to non‐sarcomatoid clear cell renal cell carcinoma. We examined the transcriptome of the epithelioid and sarcomatoid components of advanced stage sarcomatoid clear cell renal cell carcinoma (n=43) and non‐sarcomatoid clear cell renal cell carcinoma (n=37) from independent discovery and validation cohorts using the cDNA microarray and RNA‐seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays, from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and advanced non‐sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had similar gene expression and DNA copy number signatures that were, however, distinct from those of high‐grade, high‐stage non‐sarcomatoid clear cell renal cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression profiles were shared by the biphasic components of sarcomatoid clear cell renal cell carcinoma and the sarcomatoid component showed a partial epithelial‐to‐mesenchymal transition signature. Our genome‐scale microarray‐based transcript data were validated in an independent set of sarcomatoid and non‐sarcomatoid clear cell renal cell carcinomas using RNA‐seq. Sarcomatoid clear cell renal cell carcinoma is molecularly distinct from non‐sarcomatoid clear cell renal cell carcinoma, with its genetic programming largely shared by its biphasic morphological components. These data explain why a low percentage of sarcomatoid histology

  3. Tumor Enucleation for Renal Cell Carcinoma

    PubMed Central

    Malkowicz, S. Bruce

    2015-01-01

    The increased number of small renal masses (SRMs) detected annually has led to a rise in the use of nephron-sparing surgery (NSS). These techniques aim to preserve the largest amount of healthy renal tissue possible while maintaining the same oncologic outcomes as radical nephrectomy (RN). Additionally, partial nephrectomy (PN) has been linked to a lower risk of chronic kidney disease, cardiovascular morbidity, and mortality when compared to RN. There has been continual progress toward resecting less renal parenchyma. While the predominant surgical method of performing NSS is through traditional PN, simple enucleation (SE) of the tumor has increased in popularity over recent years. SE is a technique that aims to preserve the maximal amount of renal parenchyma possible by utilizing the renal tumor pseudocapsule to bluntly separate the lesion from its underlying parenchyma, offering the smallest possible margin of excised healthy renal tissue. Several studies have demonstrated the oncological safety of SE compared with PN in the treatment of SRMs, with lower overall incidence of positive surgical margins. Additionally, SE has been shown to have similar 5- and 10-year progression-free and cancer-specific survival as PN. We present a review of the literature and an argument for SE to be a routine consideration in the treatment of all renal tumors amenable to NSS.

  4. Ion pump sorting in polarized renal epithelial cells.

    PubMed

    Caplan, M J

    2001-08-01

    The plasma membranes of renal epithelial cells are divided into distinct apical and basolateral domains, which contain different inventories of ion transport proteins. Without this polarity vectorial ion and fluid transport would not be possible. Little is known of the signals and mechanisms that renal epithelial cells use to establish and maintain polarized distributions of their ion transport proteins. Analysis of ion pump sorting reveals that multiple complex signals participate in determining and regulating these proteins' subcellular localizations.

  5. [Renal Cell Carcinoma metastases in the maxillofacial area: Case series.

    PubMed

    Ruiz-Oslé, Sara; Prol, Carlos; Lardies, Rosa; Gaafar, Ayman; Barbier, Luis; Arruza, Antón

    2017-10-01

    Renal cell carcinoma is an unpredictable malignancy. Sometimes, metastases are the disease debut. On the other hand, metastases could present years after treatment of the primary tumor. Four clinical cases of atypical metastases in the head and neck location are presented: parotid gland, mandibular bone, attached molar gingiva and masticator space. Physiopathology, clinics, histology and management of metastatic renal cell carcinoma at those anatomical regions are reviewed.

  6. Occupation and renal cell cancer in Central and Eastern Europe

    PubMed Central

    Heck, Julia E; Charbotel, Barbara; Moore, Lee E; Karami, Sara; Zaridze, David G; Matveev, Vsevolod; Janout, Vladimir; Kollárová, Helena; Foretova, Lenka; Bencko, Vladimir; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Mates, Dana; Ferro, Gilles; Chow, Wong-Ho; Rothman, Nathaniel; Stewart, Patricia; Brennan, Paul; Boffetta, Paolo

    2010-01-01

    Objective Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer etiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. Methods From 1999–2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (OR) and 95% confidence intervals (CI) of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. Results A total of 992 histologically confirmed incident renal cell cancer cases and 1,465 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labor and animal husbandry (OR=1.43, 95% CI 1.05, 1.93), particularly among women employed as general farm workers (OR=2.73, 95% CI 1.05, 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR=1.89, 95% CI 1.35, 2.65), and mechanical engineers (OR=1.71, 95% CI 1.03, 2.84). Conclusions Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers. PMID:19737732

  7. Systemic adjuvant therapies in renal cell carcinoma

    PubMed Central

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  8. Emerging therapeutics in refractory renal cell carcinoma.

    PubMed

    Koshkin, Vadim S; Rini, Brian I

    2016-06-01

    Metastatic renal cell carcinoma (mRCC) has seen the introduction of numerous new treatments over the past decade. However, the efficacy of these therapies has plateaued, and new treatment options are needed for the majority of patients with mRCC whose disease inevitably progresses through one or more standard therapies ('refractory' mRCC). Recently approved agents in this space have shown great promise. This article reviews the evidence behind current management strategies for mRCC. After reviewing clinical trials that established current first-line therapies and agents used in the refractory setting, we address new ideas for the treatment of refractory disease including combination therapies and novel targeted agents. In particular, we focus on targeted immunotherapy in refractory mRCC. We conclude by considering future directions in combination treatments utilizing these novel agents. Numerous approaches have produced tangible benefits for the treatment of patients with mRCC. These include development of next generation VEGFR/TKIs, targeted immunotherapy agents, and the development of combined regimens. In particular, immunotherapy agents targeting the PD1/PD-L1 pathway have shown great promise with a robust survival advantage seen in patients treated with nivolumab. A tolerable side effect profile of immunotherapy agents makes them amenable for use in combination therapies and ongoing trials are addressing this question.

  9. Pediatric and adolescent renal cell carcinoma.

    PubMed

    Young, Ezekiel E; Brown, Christopher T; Merguerian, Paul A; Akhavan, Ardavan

    2016-01-01

    Renal cell carcinoma (RCC) is an uncommon malignancy among children and adolescents. Because of this, there has been relatively sparse research and evidence on the topic. As the body of research regarding pediatric and adolescent RCC has developed in recent years, it has become increasingly clear that it demonstrates important differences from the much more common adult-type RCC. This review aims to examine and summarize the current literature, with a focus on the ways that pediatric and adolescent RCC differ from the adult disease, and to make recommendations for evaluation and management based on this evidence whenever possible. A thorough search of all articles relating to pediatric and adolescent RCC has been undertaken using PubMed. The reference lists from all relevant articles have been further reviewed, to ensure inclusion of all pertinent literature. The most significant development in recent years has been the realization that most of the pediatric and adolescent RCC cases, but only a very small fraction of adult RCC cases, demonstrate "translocation tumor" pathology. It is likely that such differences may eventually explain many of the previous observations regarding differences in behavior of RCC among children and teenagers. At this point, however, the relevance of translocation pathology to clinical management remains unclear, and so most continue to treat these patients in much the same way as those with the more conventional tumor subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Percutaneous radiofrequency ablation of renal cell carcinoma.

    PubMed

    Chiou, Yi-You; Hwang, Jen-I; Chou, Yi-Hong; Wang, Jia-Hwia; Chiang, Jen-Huey; Chang, Cheng-Yen

    2005-05-01

    Preliminary data regarding the use of percutaneous radiofrequency ablation (RFA) for the treatment of renal cell carcinoma (RCC) are encouraging, and show the technique to be associated with minimal morbidity. Thus, the current study was designed to evaluate the clinical applications, treatment efficacy, and complications of percutaneous RFA in RCC. From February 2003 to February 2004, 12 consecutive patients with histopathologically proven RCC underwent imaging-guided percutaneous RFA. The mean age of the patients (8 men and 4 women) was 76 years (range, 56-87 years), and mean tumor diameter was 3.7 cm (range, 2.2-8.0 cm). The efficacy of RFA was evaluated with contrast-enhanced, dynamic computed tomography (CT) performed 1 month after treatment, and then every 3 months. A Radionics device with an internally cooled electrode was used in 7 patients, and a radiofrequency interstitial tissue ablation (RITA) device with an expandable needle electrode was used in 5. Complete necrosis was defined as a lack of contrast enhancement in the treated region on follow-up CT studies. Overall, 16 sessions of RFA were performed for 12 solitary renal tumors in 12 patients: 8 patients underwent a single RFA session, whereas 4 had 2 sessions. Dynamic CT after RFA showed complete necrosis in 9 of 12 tumors. In 3 patients with tumors of 4.5-8.0 cm in diameter, enhancement of residual tissue was observed after RFA treatment, thus indicating residual tumor. Complete tumor necrosis was seen in all 5 tumors (100%) of diameter < or = 3.0 cm; 3 of 4 tumors (75%) of diameter 3.1-5.0 cm; and 1 of 3 tumors (33%) of diameter > 5.0 cm. A big subcapsular hematoma, which was found in 1 patient after RFA, resolved completely within 10 months without treatment; no serious complications occurred in the other 11 patients. Percutaneous RFA is effective in the treatment of RCC. It is most successful for tumors not larger than 3 cm in diameter, and has a satisfactory success rate in tumors of 3-5 cm in

  11. Meat-cooking mutagens and risk of renal cell carcinoma

    PubMed Central

    Daniel, C R; Schwartz, K L; Colt, J S; Dong, L M; Ruterbusch, J J; Purdue, M P; Cross, A J; Rothman, N; Davis, F G; Wacholder, S; Graubard, B I; Chow, W H; Sinha, R

    2011-01-01

    Background: High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case–control study conducted in metropolitan Detroit and Chicago. Methods: Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database. Results: The risk of RCC increased with intake of barbecued meat (Ptrend=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), Ptrend=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (Pinteraction<0.05). We found no association for HCAs or overall meat intake. Conclusion: BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC. PMID:21897389

  12. [Spectrum of renal manifestations in sickle cell disease].

    PubMed

    Cazenave, Maud; Koehl, Bérengère; Nochy, Dominique; Tharaux, Pierre-Louis; Audard, Vincent

    2014-02-01

    Sickle cell disease (SCD), the most common hemoglobinopathy, is an increasing cause of chronic kidney disease. In the last decade, we have witnessed a better understanding in the characterization of clinical manifestations and pathogenesis of sickle cell nephropathy. The spectrum of renal diseases during SCD includes various renal manifestations such as impairment of urinary concentrating ability, defect in urine acidification, renal papillary necrosis and proteinuria related to glomerular injury leading to progressive end-stage renal disease. Endothelial dysfunction related to chronic hemolysis and the relative renal hypoxia caused by vaso-occlusive sickle red blood cells are probably two key factors for SCN development. Optimal therapeutic management (including the use of blockers of the renin-angiotensin system) of patients with proteinuria remains to be determined. Renal replacement therapy with dialysis is required in SCD patients with end-stage renal disease but these patients should probably undergo kidney transplantation that requires careful management. Copyright © 2013 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  13. Simultaneous development of renal cell carcinoma and multifocal urothelial carcinoma.

    PubMed

    Chuang, Heng-Chang; Chuang, Cheng-Keng; Ng, Kwai-Fong

    2008-01-01

    Simultaneous occurrence of multifocal urothelial carcinoma (UC) and ipsilateral renal cell carcinoma (RCC) is rare. We report a 67-year-old woman with multifocal, infiltrating urothelial carcinoma and unilateral renal cell carcinoma. She was referred to our department because of painless gross hematuria. Cystoscopy, computed tomography and retrograde pyelography studies revealed bladder, bilateral renal and ureter UC. She was treated with transurethral resection of the bladder tumor followed by bilateral nephroureterectomy. The pathological diagnosis was high-grade UC over the bladder and both renal pelves and ureters. A second tumor in the upper pole of the right kidney was reported as clear cell RCC. The patient was alive and still under careful surveillance at this writing.

  14. Transport of circulating serum cholesterol by human renal cell carcinoma

    SciTech Connect

    Clayman, R.V.; Figenshau, R.S.; Prigge, W.F.; Forstrom, L.; Gebhard, R.L.

    1987-06-01

    Clear cell renal cancer contains a large quantity of cholesterol ester (300-mg./gm. protein). To determine whether abnormalities in cholesterol transport could account for this sterol accumulation, the uptake, release, and imaging capabilities of intravenously injected /sup 131/I-6-iodomethyl-29-norcholesterol, a cholesterol analogue, were studied preoperatively in five patients with clear cell renal cancer. At surgery, samples of the liver, tumor, adrenal, and non-tumor kidney were obtained for analysis. /sup 131/I-sterol uptake by the tumor, when normalized for cholesterol content, was less than for adrenal, liver or kidney. In contrast, release of preloaded /sup 131/I-sterol from the human tumors was consistently slower than for normal kidney. The reduced release of free cholesterol from renal cancer cells may, in part, be responsible for the accumulation of cholesterol in human renal cancer.

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

    PubMed

    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.

  16. Fetal kidney stem cells ameliorate cisplatin induced acute renal failure and promote renal angiogenesis

    PubMed Central

    Gupta, Ashwani Kumar; Jadhav, Sachin H; Tripathy, Naresh Kumar; Nityanand, Soniya

    2015-01-01

    AIM: To investigate whether fetal kidney stem cells (fKSC) ameliorate cisplatin induced acute renal failure (ARF) in rats and promote renal angiogenesis. METHODS: The fKSC were isolated from rat fetuses of gestation day 16 and expanded in vitro up to 3rd passage. They were characterized for the expression of mesenchymal and renal progenitor markers by flow cytometry and immunocytochemistry, respectively. The in vitro differentiation of fKSC towards epithelial lineage was evaluated by the treatment with specific induction medium and their angiogenic potential by matrigel induced tube formation assay. To study the effect of fKSC in ARF, fKSC labeled with PKH26 were infused in rats with cisplatin induced ARF and, the blood and renal tissues of the rats were collected at different time points. Blood biochemical parameters were studied to evaluate renal function. Renal tissues were evaluated for renal architecture, renal cell proliferation and angiogenesis by immunohistochemistry, renal cell apoptosis by terminal deoxynucleotidyl transferase nick-end labeling assay and early expression of angiogenic molecules viz. vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α and endothelial nitric oxide synthase (eNOS) by western blot. RESULTS: The fKSC expressed mesenchymal markers viz. CD29, CD44, CD73, CD90 and CD105 as well as renal progenitor markers viz. Wt1, Pax2 and Six2. They exhibited a potential to form CD31 and Von Willebrand factor expressing capillary-like structures and could be differentiated into cytokeratin (CK)18 and CK19 positive epithelial cells. Administration of fKSC in rats with ARF as compared to administration of saline alone, resulted in a significant improvement in renal function and histology on day 3 (2.33 ± 0.33 vs 3.50 ± 0.34, P < 0.05) and on day 7 (0.83 ± 0.16 vs 2.00 ± 0.25, P < 0.05). The infused PKH26 labeled fKSC were observed to engraft in damaged renal tubules and showed increased proliferation and reduced

  17. Potential relationship between BK virus and renal cell carcinoma.

    PubMed

    Bulut, Yasemin; Ozdemir, Enver; Ozercan, Halil Ibrahim; Etem, Ebru Onalan; Aker, Fugen; Toraman, Zulal Asci; Seyrek, Adnan; Firdolas, Fatih

    2013-06-01

    The objective of the present study was to investigate the potential association between the presence of BK virus (BKV) DNA and mRNA and renal cell carcinoma and bladder transitional cell carcinoma. The formalin-fixed and paraffin-embedded tissue samples were obtained from 50 cancer patients with renal cell carcinoma, 40 cancer patients with bladder transitional cell carcinoma, 45 control patients with the benign renal pathology, and from another 25 control patients with benign bladder pathology. The samples were subjected to nested PCR for detection of BKV DNA and real-time reverse transcription PCR (real-time RT-PCR) for determining mRNA levels of BKV. The results of the nested PCR indicated that 23 (14.3%) of 160 samples were positive for BKV DNA. The relationship between the cancer and the presence of BKV DNA was significant (P < 0.05). The BKV DNA positivity was significantly associated with the histological diagnosis of renal cell carcinoma (P = 0.03), but not with that of bladder transitional cell carcinoma. The results of real-time RT-PCR showed that the mRNA of BKV VP1 was present in 69.5% of the BKV DNA positive samples. The levels of BKV mRNA were significantly higher in the renal cell cancer samples than in the control samples (P < 0.05). The results of the present study confirm the association between BKV and renal cell cancer. The findings also indicated that the presence of BKV DNA resulted in a fivefold increase in the risk of development of renal cell carcinoma.

  18. [Tripeptides slow down aging process in renal cell culture].

    PubMed

    Khavinson, V Kh; Tarnovskaia, S I; Lin'kova, N S; Poliakova, V O; Durnova, A O; Nichik, T E; Kvetnoĭ, I M; D'iakonov, M M; Iakutseni, P P

    2014-01-01

    The mechanism of geroprotective effect of peptides AED and EDL was studied in ageing renal cell culture. Peptide AED and EDL increase cell proliferation, decreasing expression of marker of aging p16, p21, p53 and increasing expression of SIRT-6 in young and aged renal cell culture. The reduction of SIRT-6 synthesis in cell is one of the causes of cell senescence. On the basis of experimental data models of interaction of peptides with various sites of DNA were constructed. Both peptides form most energetically favorable complexes with d(ATATATATAT)2 sequences in minor groove of DNA. It is shown that interaction of peptides AED and EDL with DNA is the cause of gene expression, encoded marker of ageing in renal cells.

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

    PubMed

    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.

  20. Expression of S-100 protein in renal cell neoplasms.

    PubMed

    Lin, Fan; Yang, Wannian; Betten, Mark; Teh, Bin Tean; Yang, Ximing J

    2006-04-01

    Polyclonal antibody to S-100 protein has been routinely applied for initial screening of various types of tumors, including, melanocytic tumors and neurogenic tumors. S-100 protein has been shown to have a broad distribution in human tissues, including renal tubules. The potential utility of S-100 protein in renal cell neoplasms has not been extensively investigated. Using an EnVision-Horseradish Peroxidase (HRP; Dako, Carpinteria, Calif) kit, we evaluated the diagnostic value of S-100 protein on tissue microarray sections from 175 cases of renal epithelial neoplasm (145 primary renal neoplasms and 30 metastatic renal cell carcinomas) and 24 non-neoplastic renal tissues. Immunohistochemical stains for pancytokeratin, HMB-45, and Mart-1 were also performed. Western blot using the same antibody (anti-S-100 protein) was performed on 10 cases of renal cell neoplasm. The results demonstrated that nuclear and cytoplasmic staining pattern for S-100 protein was observed in 56 (69%) of 81 conventional (clear cell) renal cell carcinomas (RCCs), 10 (30%) of 33 papillary RCCs, 1 (6%) of 16 ChRCCs, and 13 (87%) of 15 oncocytomas. Among the 81 cases of CRCC, positivity for S-100 protein was seen in 41 (71%) of 58 and 15 (65%) of 23 cases with Furhman nuclear grade I/II and III/IV, respectively. Focal immunostaining was present in 22 (92%) of 24 normal renal tubules. Similar staining pattern was observed in 21 (70%) of 30 metastatic RCCs. Western blotting demonstrated the S-100 protein expression in both renal cell neoplasm and normal renal tissue. Overexpression of S-100 in oncocytomas compared with ChRCCs was confirmed by the data of Western blot and cDNA microarray analysis. Importantly, 14.8% (12/81) of clear cell RCC and 13.3% (4/30) of metastatic RCC revealed an immunostaining profile of pancytokeratin (-)/S-100 protein (+). These data indicate that caution should be taken in interpreting an unknown primary with S-100 positivity and cytokeratin negativity. In addition, it

  1. Hereditary leiomyomatosis and renal cell cancer syndrome: a family affair.

    PubMed

    Teh, Jiasian; Kinnear, Ned; Douglass-Molloy, Hannah; Hennessey, Derek Barrry

    2017-01-25

    A 49-year-old woman with cutaneous and uterine leiomyomas, flank pain and a family history of hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome sought genetic testing. She was found to harbour a fumarate hydratase (FH) genetic mutation and a previously undetected renal tumour. The patient underwent radical nephrectomy, and remains well at follow-up. HLRCC syndrome is a rare autosomal dominant disease, with patients at increased risk for cutaneous leiomyomas, early-onset uterine leiomyomas and aggressive renal carcinoma. Although the syndrome may manifest life-threatening complications, outcomes may be improved by preventative family screening and surveillance, compelling early diagnosis.

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

    PubMed

    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.

  3. Haematogenous dissemination of cells from human renal adenocarcinomas.

    PubMed Central

    Glaves, D.; Huben, R. P.; Weiss, L.

    1988-01-01

    Estimates were made of the rates at which cancer cells were released directly into the renal vein in patients undergoing radical nephrectomy for primary renal cancer. Cancer cells were counted in blood samples taken from the renal vein using a density gradient centrifugation procedure, and identified using immunocytochemical techniques, on the basis of their cytoskeletal intermediate filament proteins. Cancer cells were released as single cells and multicell emboli in 8/10 patients, in numbers varying widely between 14-7509 emboli ml-1 of blood. Despite a calculated median input into the metastatic process of 3.7 x 10(7) cancer cells per day for at least 180 days, only 3/10 patients had extraperitoneal metastases prior to surgery and only 1 of the remaining disease-free patients subsequently developed distant metastases over a maximum 35 month period. These results are discussed in terms of primary tumour kinetics and metastatic inefficiency. Images Figure 1 PMID:3279993

  4. Preventive effect of specific antioxidant on oxidative renal cell injury associated with renal crystal formation.

    PubMed

    Fishman, Andrew I; Green, David; Lynch, Alexandria; Choudhury, Muhammad; Eshghi, Majid; Konno, Sensuke

    2013-08-01

    To investigate whether calcium oxalate monohydrate (COM), a key element of hyperoxaluria, would induce renal cell injury through oxidative stress and also whether certain antioxidants could prevent chemically induced renal crystal formation in rats. COM-exerted oxidative stress on the kidney epithelial Madin-Darby canine kidney cells was assessed using the lipid peroxidation assay. Glyoxalase I (Gly-I) activity was also determined. Two antioxidants, vitamin C and N-acetylcysteine (NAC), were then tested to determine whether they could abolish such oxidative stress in Madin-Darby canine kidney cells. Both antioxidants were also tested to determine whether they might prevent or reduce renal crystal formation induced with ethylene glycol (EG) and vitamin D3 (VD3) in Wistar rats. COM (200 μg/mL) demonstrated ∼1.3-fold greater oxidative stress with a significant reduction in cell viability and Gly-I activity compared with controls. However, such adverse events were almost completely prevented with NAC but not with vitamin C. In the animal study, no renal crystals were seen in the sham group. However, numerous crystals, with reduced Gly-I activity and elevated oxidative stress, were found in the EG-VD3 group. However, markedly (>70%) fewer crystals, with full Gly-I activity and diminished oxidative stress, were detected in the EG-VD3+NAC group. COM exerted oxidative stress on Madin-Darby canine kidney cells, leading to cell viability reduction and Gly-I inactivation, with NAC fully preventing such adverse consequences. Similarly, numerous crystals with Gly-I inactivation and elevated oxidative stress seen in the rats (EG-VD3) were also significantly prevented with NAC supplement. Thus, NAC might have clinical implications in preventing oxidative renal cell injury and, ultimately, kidney stone formation. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level.

    PubMed

    Ma, Yabing; Ren, Zhongzhong; Ma, Shuyong; Yan, Wenjun; He, Man; Wang, Dong; Ding, Peiyan

    2017-11-01

    Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. Unfortunately, the results obtained by these studies are still contradictory. In this study, we investigated the effect of morphine in human clear cell renal cell carcinoma 786-O, RLC-310 cells and whether morphine affects on tumor growth in human clear cell renal cell carcinoma 786-O, RLC-310 cells. The cell proliferation was determined by MTT assay, cell proliferation, migration and invasion assays. Immunofluorescence staining and Q-PCR was used to determine the Survivin expression. It was shown that morphine enhances proliferation of 786-O, RLC-310 cells, whereas morphine promoted the growth and aggressive phenotype of 786-O and RLC-310 cells in vitro though Survivin-dependent signaling. Our data showed that morphine promotes RCC growth and increases RCC progression via over-expression of Survivin.

  6. Keratins are novel markers of renal epithelial cell injury.

    PubMed

    Djudjaj, Sonja; Papasotiriou, Marios; Bülow, Roman D; Wagnerova, Alexandra; Lindenmeyer, Maja T; Cohen, Clemens D; Strnad, Pavel; Goumenos, Dimitrios S; Floege, Jürgen; Boor, Peter

    2016-04-01

    Keratins, the intermediate filaments of the epithelial cell cytoskeleton, are up-regulated and post-translationally modified in stress situations. Renal tubular epithelial cell stress is a common finding in progressive kidney diseases, but little is known about keratin expression and phosphorylation. Here, we comprehensively describe keratin expression in healthy and diseased kidneys. In healthy mice, the major renal keratins, K7, K8, K18, and K19, were expressed in the collecting ducts and K8, K18 in the glomerular parietal epithelial cells. Tubular expression of all 4 keratins increased by 20- to 40-fold in 5 different models of renal tubular injury as assessed by immunohistochemistry, Western blot, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The up-regulation became significant early after disease induction, increased with disease progression, was found de novo in distal tubules and was accompanied by altered subcellular localization. Phosphorylation of K8 and K18 increased under stress. In humans, injured tubules also exhibited increased keratin expression. Urinary K18 was only detected in mice and patients with tubular cell injury. Keratins labeled glomerular parietal epithelial cells forming crescents in patients and animals. Thus, all 4 major renal keratins are significantly, early, and progressively up-regulated upon tubular injury regardless of the underlying disease and may be novel sensitive markers of renal tubular cell stress. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  7. Renal coccidiosis in interior Canada geese, Branta canadensis interior Todd, of the Mississippi Valley population

    USGS Publications Warehouse

    Tuggle, Benjamin N.; Crites, John L.

    1984-01-01

    Kidneys from 309 Interior Canada geese from three locations in the Mississippi Flyway were examined for renal coccidia. Oocysts and/or young zygotes of Eimeria sp. were found in 6.8% of goose kidneys sampled. Only one type of renal coccidian oocyst was observed. Significantly more immature geese were infected than adults; however, there was no significant difference observed between the prevalences of infection in male and female birds. A host cellular response to zygotes and oocysts was noted in the majority of infected adult geese. Heavily infected kidneys were hypertrophic with minute foci on the surface of the organ. Histological examinations showed large numbers of unsporulated oocysts accumulated in distended collecting tubules, resulting in pressure necrosis to adjacent tissue and urate retention. Zygotes were observed in the cytoplasm of tubule cells and extracellularly in interstitial tissue. Infected tubule cells were characterized by the peripheral location of the nuclei, cytoplasmic basophilia, and cellular hypertrophy. This is the first report of an Eimeria sp. in the kidneys of Canada geese of the Mississippi Valley population.

  8. Atherosclerotic ischemic renal disease. Diagnosis and prevalence in an hypertensive and/or uremic elderly population

    PubMed Central

    Coen, Giorgio; Calabria, Santo; Lai, Silvia; Moscaritolo, Eleonora; Nofroni, Italo; Ronga, Giuseppe; Rossi, Michele; Ventroni, Guido; Sardella, Daniela; Ferrannini, Michele; Zaccaria, Alvaro; Cianci, Rosario

    2003-01-01

    Background Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; Its prevalence is inferred from autopsy or retrospective arteriographic studies. This study has been conducted on 269 subjects over 50 with hypertension and/or CRF, unrelated to other known causes of renal disease. Methods All 269 patients were studied either by color-flow duplex sonography (n = 238) or by renal scintigraphy (n = 224), and 199 of the 269 patients were evaluated using both of these techniques. 40 patients, found to have renal artery stenosis (RAS), were subjected to 3D-contrast enhancement Magnetic Resonance Angiography (MRA) and/or Selective Angiography (SA). An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or SA). Results Color-duplex sonography, carried out in 238 patients, revealed 49 cases of RAS. MR or SA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography showed a PPV value of 94.3% and NPV of 87.0% while renal scintigraphy, carried out in 224 patients, had a PPV of 72.2% and a NPV of 29.4%. Patients with RAS showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in proteinuria. RAS, based on color-duplex sonography studies, was present in 11% of patients in the age group 50–59, 18% in the 60–69 and 23% at age 70 and above. Conclusions A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by RAS and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis. PMID:12622875

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

    PubMed

    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.

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

    PubMed

    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.

  11. Lithium causes G2 arrest of renal principal cells.

    PubMed

    de Groot, Theun; Alsady, Mohammad; Jaklofsky, Marcel; Otte-Höller, Irene; Baumgarten, Ruben; Giles, Rachel H; Deen, Peter M T

    2014-03-01

    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 (NDI), a disorder characterized by polyuria and polydipsia. Lithium-induced NDI is caused by aquaporin-2 downregulation and a reduced ratio of principal/intercalated cells, yet lithium induces principal cell proliferation. Here, we studied how lithium-induced principal cell proliferation can lead to a reduced ratio of principal/intercalated cells using two-dimensional and three-dimensional polarized cultures of mouse renal collecting duct cells and mice treated with clinically relevant lithium concentrations. DNA image cytometry and immunoblotting revealed that lithium initiated proliferation of mouse renal collecting duct cells but also increased the G2/S ratio, indicating G2/M phase arrest. In mice, treatment with lithium for 4, 7, 10, or 13 days led to features of NDI and an increase in the number of principal cells expressing PCNA in the papilla. Remarkably, 30%-40% of the PCNA-positive principal cells also expressed pHistone-H3, a late G2/M phase marker detected in approximately 20% of cells during undisturbed proliferation. Our data reveal that lithium treatment initiates proliferation of renal principal cells but that a significant percentage of these cells are arrested in the late G2 phase, which explains the reduced principal/intercalated cell ratio and may identify the molecular pathway underlying the development of lithium-induced renal fibrosis.

  12. Lithium Causes G2 Arrest of Renal Principal Cells

    PubMed Central

    de Groot, Theun; Alsady, Mohammad; Jaklofsky, Marcel; Otte-Höller, Irene; Baumgarten, Ruben; Giles, Rachel H.

    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 (NDI), a disorder characterized by polyuria and polydipsia. Lithium-induced NDI is caused by aquaporin-2 downregulation and a reduced ratio of principal/intercalated cells, yet lithium induces principal cell proliferation. Here, we studied how lithium-induced principal cell proliferation can lead to a reduced ratio of principal/intercalated cells using two-dimensional and three-dimensional polarized cultures of mouse renal collecting duct cells and mice treated with clinically relevant lithium concentrations. DNA image cytometry and immunoblotting revealed that lithium initiated proliferation of mouse renal collecting duct cells but also increased the G2/S ratio, indicating G2/M phase arrest. In mice, treatment with lithium for 4, 7, 10, or 13 days led to features of NDI and an increase in the number of principal cells expressing PCNA in the papilla. Remarkably, 30%–40% of the PCNA-positive principal cells also expressed pHistone-H3, a late G2/M phase marker detected in approximately 20% of cells during undisturbed proliferation. Our data reveal that lithium treatment initiates proliferation of renal principal cells but that a significant percentage of these cells are arrested in the late G2 phase, which explains the reduced principal/intercalated cell ratio and may identify the molecular pathway underlying the development of lithium-induced renal fibrosis. PMID:24408872

  13. Clear cell renal cell carcinoma with intratumoral and nodal extramedullary megakaryopoiesis: a potential diagnostic pitfall.

    PubMed

    Williamson, Sean R; Mast, Kelley J; Cheng, Liang; Idrees, Muhammad T

    2014-06-01

    Clear cell renal cell carcinoma is occasionally associated with erythrocytosis, hypothesized to result from tumoral production of erythropoietin. Rarely, intratumoral erythropoiesis has been identified, although intratumoral megakaryopoiesis has not, to our knowledge, been previously described. We report the case of an 81-year-old man with myelofibrosis who underwent resection of a 9.8-cm clear cell renal cell carcinoma. Numerous megakaryocytes were present within the renal cell carcinoma; regional lymph nodes; and, to a lesser extent, the nonneoplastic kidney, glomeruli, and renal hilar soft tissue, in some areas associated with trilineage hematopoiesis. Immunohistochemistry verified the megakaryocytic lineage of the atypical cells (CD61, CD42b, and von Willebrand factor +; cytokeratin -). Intratumoral extramedullary megakaryopoiesis is a novel finding in clear cell renal cell carcinoma with potential to mimic high-grade carcinoma and involvement of lymph nodes. Careful attention to morphology, presence of other hematopoietic elements, and immunoprofile can facilitate recognition of this rare phenomenon.

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

    PubMed Central

    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

  15. Properties of B cells and Thy-1-antigen-expressing cells infiltrating rat renal allografts

    SciTech Connect

    Leszczynski, D.; Halttunen, J.; Tiisala, S.; Ustinov, J.; Renkonen, R.; Haeyry, P. )

    1990-10-01

    We have examined (1) the frequency of B cells secreting antibodies against donor major histocompatibility complex (MHC) antigens and (2) the properties of Thy-1-antigen-expressing leukocytes in rats rejecting renal allografts. Our results show that B cells secreting antibodies are present in the inflammatory cell population at the frequency of 1:850. Among them only 1 out of 2-150 is engaged in production of antibodies directed to the graft MHC antigens, depending on the method of assay. This suggests that despite the observed significant production of nonspecific immunoglobulin in situ, only a minority of the B-cell population is specifically committed to the graft MHC antigens. This finding is concordant with the described previously low frequencies of the T cells specifically directed toward the graft MHC antigen. The role of the immunologically noncommitted cells in graft rejection is unknown. We have found that a substantial part (up to 60%) of inflammatory cells invading a rat kidney allograft express the Thy-1 antigen. This suggests that they might be immature (progenitor ) cells and, therefore, unable to respond to the graft antigens. Progenitor-like properties of these cells have been confirmed by their ability to reconstitute lethally irradiated syngeneic rat. Finally, these immature cells are of lymphoid, not of myeloid, linkage, because they do not proliferate in the presence of GM-CSF.

  16. Oncocytic papillary renal cell carcinoma with solid architecture: mimic of renal oncocytoma.

    PubMed

    Mai, Kien T; Kohler, Derek M; Robertson, Susan J; Belanger, Eric C; Marginean, E Celia

    2008-03-01

    Papillary renal cell carcinoma (PRCC) can display extensive areas of solid and non-papillary architecture and extensive areas with oncocytic cytoplasm. Eleven oncocytic renal cell neoplasms (ORCN) with histopathological features posing a diagnostic problem between renal cell carcinoma (RCC) with oncocytic features and renal oncocytoma (RO) were identified. The neoplasms were well circumscribed or encapsulated tumors with solid and diffuse growth pattern. Very occasional papillae were seen in four and tumoral necrosis in two of 11. Six ORCN displayed a CD117+/progesterone receptor (PR)+ immunophenotype (feature shared by RO) and five tumors displayed a CD117-/PR- immunophenotype (feature shared by RCC). The CD117-/PR- ORCN also displayed alpha-methylacyl-coenzyme A racemase and RCC antigen reactivity as well as varying reactivity for cytokeratin 7, vimentin and CD10 (features of oncocytic PRCC). These five cases had tumor sizes ranging from 1 to 6 cm. Two patients in the latter group developed progression of the disease with metastases. In conclusion, oncocytic PRCC with solid architecture is a rare type of RCC. The carcinoma often poses differential diagnostic problems with RO and has similar immunohistochemical properties to the common type of PRCC. Cytogenetic and molecular studies have not been performed yet for this variant of RCC.

  17. Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment.

    PubMed

    Hira, Daiki; Chisaki, Yugo; Noda, Satoshi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi; Yano, Yoshitaka; Morita, Shin-Ya; Terada, Tomohiro

    2015-01-01

    The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m(2), including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment. © 2015 S. Karger AG, Basel.

  18. Renal cell carcinoma in kidney allografts: histologic types, including biphasic papillary carcinoma.

    PubMed

    Troxell, Megan L; Higgins, John P

    2016-11-01

    Kidney transplant recipients are at increased risk for malignancy, with about 5% incidence of cancer in native end-stage kidneys. Carcinoma in the renal allograft is far less common. Prior studies have demonstrated a propensity for renal cell carcinomas (RCCs) of papillary subtypes in end-stage kidneys, and perhaps in allograft kidneys, but most allograft studies lack detailed pathologic review and predate the current classification system. We reviewed our experience with renal carcinoma in kidney allografts at 2 academic centers applying the International Society of Urological Pathology classification, informed by immunohistochemistry. The incidence of renal allograft carcinoma was about 0.26% in our population. Of 12 allograft carcinomas, 6 were papillary (50%), 4 were clear cell (33%), 1 was clear cell (tubulo)papillary, and 1 chromophobe. Two of the papillary carcinomas had distinctive biphasic glomeruloid architecture matching the newly named "biphasic squamoid alveolar" pattern and were difficult to classify on core biopsies. The 2 cell types had different immunophenotypes in our hands (eosinophilic cells: RCC-/CK34betaE12+ weight keratin +/cyclin D1+; clear cells: RCC+/cytokeratin high molecular weight negative to weak/cyclin D1-). None of the patients experienced cancer recurrences or metastasis. Our study confirms the predilection for papillary RCCs in kidney allografts and highlights the occurrence of rare morphologic variants. Larger studies are needed with careful pathologic review, which has been lacking in the literature.

  19. Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma.

    PubMed

    Baldan, V; Griffiths, R; Hawkins, R E; Gilham, D E

    2015-04-28

    Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue. Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity. Enzymatic or combined enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being liberated from renal cell carcinoma biopsies. Following mitogenic activation of the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell recognition of autologous tumours was enhanced when tumours were disaggregated using the GentleMACS enzymatic/mechanical system. TILs can be consistently produced from renal cell carcinoma biopsies maintaining autologous tumour recognition after expansion in vitro. While the method of disaggregation has little impact on the success of TIL growth, methods that preserve the cell surface architecture facilitate TIL recognition of an autologous tumour, which is important in terms of characterising the functionality of the expanded TIL population.

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

    PubMed

    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.

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

    PubMed

    Rombo, Roman; Weiher, Hans; Schmidt-Wolf, Ingo G H

    2016-01-01

    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 selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- 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.

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

    PubMed Central

    Rombo, Roman; Weiher, Hans; Schmidt-Wolf, Ingo G.H.

    2016-01-01

    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 selective ex vivo anti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative CD4-/CD8- 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. PMID:27141211

  3. Renal Neoplasms With Overlapping Features of Clear Cell Renal Cell Carcinoma and Clear Cell Papillary Renal Cell Carcinoma: A Clinicopathologic Study of 37 Cases From a Single Institution.

    PubMed

    Dhakal, Hari P; McKenney, Jesse K; Khor, Li Yan; Reynolds, Jordan P; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-02-01

    Clear cell papillary renal cell carcinoma (CCPRCC) was recently included in the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia as a subtype of RCC that is morphologically, immunohistochemically, and genetically distinct from both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma. In our clinical practice we have observed tumors with overlapping histologic features of CCPRCC and CCRCC; therefore, our aim was to describe the morphologic, immunohistochemical, and clinical characteristics of these tumors. We examined a large series of consecutive nephrectomies diagnosed as CCRCC and found 37 tumors with morphologic overlap between CCRCC and CCPRCC, identifying 2 patterns. Pattern 1 tumors (N=19) had areas diagnosable as CCRCC admixed with foci having a prominent linear arrangement of nuclei away from the basement membrane imparting a resemblance to CCPRCC; however, other morphologic features commonly seen in CCPRCC (such as branching acini and cystic spaces with papillary tufts) were not typical and, when present, were focal or poorly developed. Pattern 2 (N=18) tumors had 2 discrete areas, one area with an appearance strongly resembling CCPRCC and the other with higher grade nuclei and features diagnosable as CCRCC, sometimes including rhabdoid differentiation, sarcomatoid differentiation, necrosis, and high-stage disease. Four (21%) of the pattern 1 tumors had grade 3 nuclei in the CCRCC-like areas, and 4 were high stage (pT3a). Of the 16 immunostained pattern 1 tumors, all expressed cytokeratin 7 (CK7) at least focally in the CCPRCC-like areas, strongly and diffusely in 9 (56%) cases; 12 (75%) showed negative to focal and/or weak CK7 expression in the CCRCC-like areas. CD10, α-methylacyl-CoA-racemase, high-molecular-weight cytokeratin, and carbonic anhydrase IX (CA IX) had no significant differential expression between these foci. No cup-like staining pattern was seen with CA IX. Two (11%) patients

  4. Tubular cell apoptosis and cidofovir-induced acute renal failure.

    PubMed

    Ortiz, Alberto; Justo, Pilar; Sanz, Ana; Melero, Rosa; Caramelo, Carlos; Guerrero, Manuel Fernández; Strutz, Frank; Müller, Gerhard; Barat, Antonio; Egido, Jesus

    2005-01-01

    Cidofovir is an antiviral drug with activity against a wide array of DNA viruses including poxvirus. The therapeutic use of cidofovir is marred by a dose-limiting side effect, nephrotoxicity, leading to proximal tubular cell injury and acute renal failure. Treatment with cidofovir requires the routine use of prophylactic measures. A correct knowledge of the cellular and molecular mechanisms of cidofovir toxicity may lead to the development of alternative prophylactic strategies. We recently cared for a patient with irreversible acute renal failure due to cidofovir. Renal biopsy showed tubular cell apoptosis. Cidofovir induced apoptosis in primary cultures of human proximal tubular cells in a temporal (peak apoptosis at 7 days) and concentration (10-40 microg/ml) pattern consistent with that of clinical toxicity. Apoptosis was identified by the presence of hypodiploid cells, by the exposure of annexin V binding sites and by morphological features and was associated with the appearance of active caspase-3 fragments. Cell death was specific as it was also present in a human proximal tubular epithelial cell line (HK-2), but not in a human kidney fibroblast cell line, and was prevented by probenecid. An inhibitor of caspase-3 (DEVD) prevented cidofovir apoptosis. The survival factors present in serum, insulin-like growth factor-1 and hepatocyte growth factor, were also protective. The present data suggest that apoptosis induction is a mechanism contributing to cidofovir nephrotoxicity. The prophylactic administration of factors with survival activity for tubular epithelium should be further explored in cidofovir renal injury.

  5. Renal stem cell reprogramming: Prospects in regenerative medicine

    PubMed Central

    Morales, Elvin E; Wingert, Rebecca A

    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 gene activity 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. PMID:25258667

  6. Renal Failure in Sickle Cell Disease: Prevalence, Predictors of Disease, Mortality and Effect on Length of Hospital Stay.

    PubMed

    Yeruva, Sri L H; Paul, Yonette; Oneal, Patricia; Nouraie, Mehdi

    2016-09-01

    Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk of developing renal dysfunction is not known. We used the Truven Health MarketScan(®) Medicaid Databases from 2007 to 2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.

  7. MET Inhibition in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Xie, Zuoquan; Lee, Young H.; Boeke, Marta; Jilaveanu, Lucia B.; Liu, Zongzhi; Bottaro, Donald P.; Kluger, Harriet M.; Shuch, Brian

    2016-01-01

    Background: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. Methods: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway. We evaluated the in vitro effects of Cabozantinib, a dual MET/VEGFR2 inhibitor, using a panel of ccRCC cell lines. Drug effects of cell viability and proliferation, migration, cell scatter, anchorage independent growth, and downstream MET/VEGFR2 signaling pathways were assessed. Results: Twelve percent of TCGA cases had possible MET/HGF oncogenic alterations with co-occurrence noted (p<0.001). MET/HGF altered cases had worse overall survival (p=0.044). Cabozantinib was a potent inhibitor of MET and VEGFR2 in vitro in our cell line panel. PI3K, MAPK and mTOR pathways were also suppressed by cabozantinib, however the effects on cell viability in vitro were modest. At nanomolar concentrations of cabozantinib, HGF-stimulated migration, invasion, cellular scattering and soft agar colony formation were inhibited. Conclusions: We provide further preclinical rationale for dual MET/VEGFR2 inhibition in ccRCC. While the MET pathway is implicated in VEGFR resistance, dual inhibitors may have direct anti-tumor effects in a patient subset with evidence of MET pathway involvement. Cabozantinib is a potent dual MET/VEGFR2 inhibitor, significantly inhibits cell migration and invasion in vitro and likely has anti-angiogenic effects similar to other VEGFR tyrosine kinase inhibitors. Future work involving in vivo models will be useful to better define mechanisms of potential anti-tumor activity. PMID:27390595

  8. Serum Creatinine Levels Are Significantly Influenced by Renal Size in the Normal Pediatric Population

    PubMed Central

    Di Zazzo, Giacomo; Stringini, Gilda; Matteucci, Maria Chiara; Muraca, Maurizio; Malena, Saverio

    2011-01-01

    Summary Background and objectives Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children. Design, setting, participants, & measurements A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender. Results When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements. Conclusions These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship. PMID:20884775

  9. Serum creatinine levels are significantly influenced by renal size in the normal pediatric population.

    PubMed

    Di Zazzo, Giacomo; Stringini, Gilda; Matteucci, Maria Chiara; Muraca, Maurizio; Malena, Saverio; Emma, Francesco

    2011-01-01

    Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children. A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender. When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements. These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship.

  10. Imaging the clear cell renal cell carcinoma proteome

    PubMed Central

    Morgan, Todd M.; Seeley, Erin H.; Fadare, Oluwole; Caprioli, Richard M.; Clark, Peter E.

    2012-01-01

    Introduction A key barrier to identification of tissue biomarkers of clear cell renal cell carcinoma (ccRCC) is the heterogeneity of protein expression within tissue. However, by providing spectra for every 0.05 mm2 area of tissue, imaging mass spectrometry (IMS) reveals the spatial distribution of peptides. We sought to determine whether this approach could be used to identify and map protein signatures of ccRCC. Methods We constructed two tissue microarrays (TMA) with two cores each of matched tumor and normal tissue from nephrectomy specimens of 70 patients with ccRCC. Samples were analyzed by matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometry (MS). Peptide signatures were identified within each TMA that differentiated cancer from normal tissue and then cross-validated. MS/MS sequencing was performed to determine identities of select differentially expressed peptides, and immunohistochemistry was used for validation. Results Peptide signatures were identified that demonstrated a classification accuracy within each TMA of 94.7–98.5% for each 0.05mm2 spot (spectrum) and 96.9–100% for each tissue core. Cross-validation across TMA's revealed classification accuracies of 82.6–84.7% for each spot and 88.9–92.4% for each core. We identified vimentin, histone 2A.X, and alpha-enolase as proteins with greater expression in cancer tissue, and validated this by immunohistochemistry. Conclusions IMS was able to identify and map specific peptides that accurately distinguished malignant from normal renal tissue, demonstrating its potential as a novel, high-throughput approach to ccRCC biomarker discovery. Given the multiple pathways and known heterogeneity involved in tumors such as ccRCC, multiple peptide signatures that maintain their spatial relationships may outperform traditional protein biomarkers. PMID:23009866

  11. Renal cell carcinoma presenting as a simple renal cyst: A case report.

    PubMed

    Yu, Yanlan; Ma, Liang; Wang, Zhenghui; Zhang, Zhigen

    2017-04-01

    Cases of renal cell carcinoma (RCC) presenting as a simple cyst are extremely rare. We herein report the case of a patient with RCC diagnosed as a simple renal cyst preoperatively. A 39-year-old female patient presented with abdominal pain for 3 months. Ultrasonography and contrast-enhanced computed tomography revealed a simple cyst in the left kidney. The patient underwent laparoscopic decortication of the renal cyst. Biochemical analysis of the cystic fluid revealed unusually low levels of potassium, sodium, calcium and glucose, and the histological examination of the floor of the cyst indicated malignancy. Laparoscopic nephrectomy was performed 20 days later and the pathological examination confirmed the diagnosis of RCC of the clear cell type. At the 2-year follow-up, the patient remained well and recurrence-free on imaging. The aim of the present study was to emphasize the importance of recognizing that RCC may occur in what appears to be a simple renal cyst based on imaging results. Biochemical analysis of the cystic fluid may help identify the presence of malignancy.

  12. Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction.

    PubMed

    Tapmeier, Thomas T; Fearn, Amy; Brown, Kathryn; Chowdhury, Paramit; Sacks, Steven H; Sheerin, Neil S; Wong, Wilson

    2010-08-01

    Tubulointerstitial fibrosis is a common consequence of a diverse range of kidney diseases that lead to end-stage renal failure. The degree of fibrosis is related to leukocyte infiltration. Here, we determined the role of different T cell populations on renal fibrosis in the well-characterized mouse model of unilateral ureteric obstruction. Depletion of CD4(+) T cells in wild-type mice with a monoclonal antibody significantly reduced the amount of interstitial expansion and collagen deposition after 2 weeks of obstruction. Reconstitution of lymphopenic RAG knockout mice with purified CD4(+) but not CD8(+) T cells, prior to ureteric obstruction, resulted in a significant increase in interstitial expansion and collagen deposition. Wild-type mice had significantly greater interstitial expansion and collagen deposition compared with lymphopenic RAG(-/-) mice, following ureteric obstruction; however, macrophage infiltration was equivalent in all groups. Thus, our results suggest that renal injury with subsequent fibrosis is likely to be a multifactorial process, with different arms of the immune system involved at different stages. In this ureteric obstruction model, we found a critical role for CD4(+) T cells in kidney fibrosis. These cells could be a potential target of therapeutic intervention to prevent excessive fibrosis and loss of function due to renal injury.

  13. Immunotherapy for metastatic renal cell carcinoma.

    PubMed

    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

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

    PubMed

    Van der Hauwaert, Cynthia; Savary, Grégoire; Buob, David; Leroy, Xavier; Aubert, Sébastien; Flamand, Vincent; Hennino, Marie-Flore; Perrais, Michaël; Lo-Guidice, Jean-Marc; Broly, Franck; Cauffiez, Christelle; Glowacki, François

    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.

  15. Multilocular Cystic Renal Cell Carcinoma or Cystic Nephroma?

    PubMed Central

    Cortez-Betancourt, Roberto; Alías-Melgar, Alejandro; Botello-Gómez, Pedro Jair; Ramírez-Garduño, Emilio; Trujillo-Vázquez, Eric Iván; Torres-Santos, Yosimart; Mata-Martínez, José Antonio; Carreño- de la Rosa, Fernando

    2016-01-01

    The incidence of Multilocular cystic renal cell carcinoma (MCRCC) in literature is very low and confounding MCRCC with cystic nephroma (CN) is even more unusual. The aim of this report is to present a case of MCRCC and emphasize the importance of the preoperative radiologic evaluation and immunohistochemical staining confirmation to obtain an accurate diagnosis. A 73-year-old woman presented with a history of 4-month right flank pain. CT showed a Bosniak type III renal mass. After laparoscopic partial nephrectomy the initial report was cystic nephroma. Immunohistochemical staining was performed being positive for Epithelial Membrane Antigen thus changing the diagnosis to MCRCC. Multilocular cystic renal cell carcinoma cannot reliably be distinguished from cystic nephroma neither by physical examination nor by radiologic evaluation; immunohistochemical staining assay is useful to differentiate between these conditions allowing an accurate diagnosis and proper follow-up. PMID:28074169

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

    PubMed Central

    Wu, Yan; Kwon, Young Suk; Labib, Mina; Foran, David J.; Singer, Eric A.

    2015-01-01

    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. PMID:26609190

  17. Estimating cell populations

    NASA Technical Reports Server (NTRS)

    White, B. S.; Castleman, K. R.

    1981-01-01

    An important step in the diagnosis of a cervical cytology specimen is estimating the proportions of the various cell types present. This is usually done with a cell classifier, the error rates of which can be expressed as a confusion matrix. We show how to use the confusion matrix to obtain an unbiased estimate of the desired proportions. We show that the mean square error of this estimate depends on a 'befuddlement matrix' derived from the confusion matrix, and how this, in turn, leads to a figure of merit for cell classifiers. Finally, we work out the two-class problem in detail and present examples to illustrate the theory.

  18. Estimating cell populations

    NASA Technical Reports Server (NTRS)

    White, B. S.; Castleman, K. R.

    1981-01-01

    An important step in the diagnosis of a cervical cytology specimen is estimating the proportions of the various cell types present. This is usually done with a cell classifier, the error rates of which can be expressed as a confusion matrix. We show how to use the confusion matrix to obtain an unbiased estimate of the desired proportions. We show that the mean square error of this estimate depends on a 'befuddlement matrix' derived from the confusion matrix, and how this, in turn, leads to a figure of merit for cell classifiers. Finally, we work out the two-class problem in detail and present examples to illustrate the theory.

  19. Urothelial and Squamous Cell Carcinoma of Renal Pelvis – A Rare Case Report

    PubMed Central

    Hippargi, Surekha B.; Kumar, Mayank

    2016-01-01

    Primary malignant tumors of the renal pelvis are relatively rare. Urothelial carcinoma of renal pelvis accounts for 7% of all renal neoplasms, with Squamous Cell Carcinoma (SCC) forming a very small percentage of these cases. Urothelial and SCC of renal pelvis is still a rarer entity. This malignancy of the renal pelvis lacks the characteristic presentation of common renal cell carcinoma and usually presents at an advanced disease stage. We report a case of urothelial and SCC of renal pelvis in a 61-year-old male who presented with non-specific clinical complaints like dysuria and right flank pain. PMID:27790450

  20. Renal Masses Detected on FDG PET/CT in Patients With Lymphoma: Imaging Features Differentiating Primary Renal Cell Carcinomas From Renal Lymphomatous Involvement.

    PubMed

    Nicolau, Carlos; Sala, Evis; Kumar, Anita; Goldman, Debra A; Schoder, Heiko; Hricak, Hedvig; Vargas, Hebert Alberto

    2017-04-01

    The purpose of this study is to analyze the (18)F-FDG PET/CT features of solid renal masses detected in patients with lymphoma and to evaluate the ability of PET/CT to differentiate renal cell carcinoma (RCC) from renal lymphomatous involvement. Thirty-six patients with solid renal masses on PET/CT performed for staging or follow-up of lymphoma were evaluated retrospectively. The features recorded for each renal mass included the following standardized uptake values (SUVs) on PET/CT: the maximum SUV (SUVmax), the mean SUV (SUVmean), the ratio of the SUVmax of the tumor to that of the normal kidney cortex, the ratio of the SUVmean of the tumor to that of the normal kidney cortex, the ratio of the SUVmax of the tumor to that of the normal liver, and the ratio of the SUVmean of the tumor to that of the normal liver. Renal mass size and margins (well defined vs infiltrative) and the presence of calcifications were evaluated on CT. Renal biopsy results were used as the reference standard. Relationships between imaging parameters and histopathologic findings were assessed. Of the 36 renal masses evaluated, 22 (61.1%) were RCCs and 14 (38.9%) were renal lymphomas. All SUV metrics were higher for renal lymphomas than for RCCs (p < 0.0001, for all). All renal lymphomas had an SUVmax higher than 5.98 g/mL (median, 10.99 g/mL), whereas all RCCs had an SUVmax lower than 5.26 g/mL (median, 2.91 g/mL). No statistically significant differences in mass size or margins were found between RCCs and renal lymphoma. PET/CT features may be useful for differentiating RCCs from renal involvement in patients with lymphoma with solid renal masses.

  1. The effect of cyclosporin A on peripheral blood T cell subpopulations in renal allografts.

    PubMed Central

    Sweny, P; Tidman, N

    1982-01-01

    Treatment with cyclosporin A (CyA) produces a reversal of the normal ratio of OKT4+ (inducer type) to OKT84 (suppressor-cytotoxic type) cells so that renal allograft recipients on CyA alone develop a four-fold increase in the absolute number of circulating OKT8 positive cells. Conventional immunosuppression with azathioprine and prednisolone reduces both populations of T cells without altering the ratio of OKT4+ to OKT8+ cells. This effect of CyA may help to explain its action as an immunosuppressive agent. PMID:6210475

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

    SciTech Connect

    Van der Hauwaert, Cynthia; Savary, Grégoire; Buob, David; Leroy, Xavier; Aubert, Sébastien; Flamand, Vincent; Hennino, Marie-Flore; Perrais, Michaël; 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.

  3. Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells.

    PubMed

    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

  4. Cells Derived from Young Bone Marrow Alleviate Renal Aging

    PubMed Central

    Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji

    2011-01-01

    Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney. PMID:21965376

  5. Cells derived from young bone marrow alleviate renal aging.

    PubMed

    Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

    2011-11-01

    Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

  6. Serum osteoprotegerin and renal function in the general population: the Tromsø Study.

    PubMed

    Vik, Anders; Brodin, Ellen E; Mathiesen, Ellisiv B; Brox, Jan; Jørgensen, Lone; Njølstad, Inger; Brækkan, Sigrid K; Hansen, John-Bjarne

    2017-02-01

    Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m(2)) eGFR increased by 0.35 mL/min/1.73 m(2) (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m(2)), eGFR decreased by 1.54 (95% CI -2.06 to -1.01) per 1 SD increase in serum OPG. OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function.

  7. Serum osteoprotegerin and renal function in the general population: the Tromsø Study

    PubMed Central

    Brodin, Ellen E.; Mathiesen, Ellisiv B.; Brox, Jan; Jørgensen, Lone; Njølstad, Inger; Brækkan, Sigrid K.; Hansen, John-Bjarne

    2017-01-01

    Background Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. Methods We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. Results In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m2) eGFR increased by 0.35 mL/min/1.73 m2 (95% CI 0.13–0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m2), eGFR decreased by 1.54 (95% CI −2.06 to −1.01) per 1 SD increase in serum OPG. Conclusions OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function. PMID:28638603

  8. Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

    PubMed Central

    Czarnecka, Anna M.; Lewicki, Sławomir; Helbrecht, Igor; Brodaczewska, Klaudia; Koch, Irena; Zdanowski, Robert; Król, Magdalena; Szczylik, Cezary

    2016-01-01

    Background 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. Materials and Methods 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. Results 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

  9. Primary renal carcinoid tumour with lung metastasis misdiagnosed as renal cell carcinoma.

    PubMed

    Daboul, Nour; Monga, Dulabh; Bunker, Mark

    2016-03-07

    A 58-year-old man with a history of metastatic renal cell carcinoma (RCC) diagnosed 10 years prior, status post right nephrectomy, presented for evaluation of pulmonary nodules. A year after the nephrectomy, he had undergone cutaneous metastasectomy in the right flank area, and a further 2 years later he had had his second cutaneous metastasectomy in the right chest wall. Both cutaneous pathologies had, at the time, shown metastatic neoplasm with histological features compatible with those of the previous renal tumour. He was treated with sorafenib. 3 years later he developed asymptomatic pulmonary nodules, which gradually doubled in size over the next 2.5 years. He underwent bronchoscopy and left lower lobe biopsy. Pathology revealed a metastatic renal carcinoid/neuroendocrine tumour. Second review of the previous renal neoplasm and the cutaneous metastatic pathology showed trabecular architecture, consistent with carcinoid, but mimicking the long parallel arrays that have been described in some cases of papillary RCC. 2016 BMJ Publishing Group Ltd.

  10. Common and uncommon adult unilateral renal masses other than renal cell carcinoma

    PubMed Central

    Le, Ott; Roy, Anjali; Silverman, Paul M.; Kundra, Vikas

    2012-01-01

    Abstract Many different masses can involve the kidney other than the commonly encountered renal cell carcinoma (RCC). The purpose of this article is to review the characteristic clinical and imaging findings of common and uncommon masses that predominantly present unilaterally in the adult patient, other than RCC. Awareness of such lesions and knowing the clinical scenario is important for appropriate diagnosis and management, especially in a multidisciplinary care setting. PMID:22752221

  11. Immunohistochemical detection of major histocompatibility complex antigens and quantitative analysis of tumour-infiltrating mononuclear cells in renal cell cancer.

    PubMed Central

    Tomita, Y.; Nishiyama, T.; Fujiwara, M.; Sato, S.

    1990-01-01

    In order to investigate the anti-tumour immune responsiveness of patients with renal cell cancer (RCC), we examined 30 such patients for the degree of expression of major histocompatibility complex (MHC) class I and class II antigens on RCC and the populations of tumour-infiltrating mononuclear cells (TIM). Normal renal tubular cells expressed class I but not class II antigens. Most of the tumour cells expressed class I antigens in 25 (83%) cases, but the proportion of such cells was reduced in five cases, three of which were of granular cell type histologically. Class II antigens were detected in all specimens with class I positivity. Various numbers of TIM were detected in 25 cases, being composed mainly of T cells and a smaller number of macrophages. Examination for the phenotype of T cells showed that CD8-positive cells were the dominant population. B cells were not detected. Quantitative analysis revealed that the numbers of TIM were significantly lower in cases showing class I reduction than in those with normal class I expression. Therefore, it was clear that class I antigens were preserved in RCC cells in most cases. Furthermore, a higher rate of reduction of class I antigens was observed in cases of granular cell type, which has been reported to have a worse prognosis than the clear cell type. The present data suggest that degree of the expression of MHC class I antigen on RCC might influence the host immune responsiveness against it. Images Figure 1 Figure 2 Figure 3 PMID:2206942

  12. Metastatic renal cell carcinoma in a meningioma: a case report.

    PubMed

    Han, H S; Kim, E Y; Han, J Y; Kim, Y B; Hwang, T S; Chu, Y C

    2000-10-01

    Tumor-to-tumor metastasis is rare. We report a case of metastatic renal cell carcinoma in meningioma. A 67-year-old woman presented a two-week history of motor dysphagia and decreased short-term memory. She had undergone a left radical nephrectomy for a renal cell carcinoma 7 years ago, and had not received any adjuvant therapy. MRI disclosed a 3.0 x 3.0 x 3.0-cm sized round tentorial-based extraaxial mass with peritumoral edema in the left posterior temporal lobe. During operation, the tumor was found to be an encapsulated mass firmly attached to the tentorium. Histologically, the tumor was a meningotheliomatous meningioma extensively infiltrated by metastatic renal cell carcinoma, accompanying widespread coagulative necrosis. Immunohistochemical staining for cytokeratin revealed strong positivity only in the renal cell carcinoma component. The patient's postoperative course was uneventful. Post-operative radiation therapy was applied to the whole brain. Three months after operation, the patient developed right hemiparesis and dysphagia. Brain MRI at that time did not reveal recurrence or any other causative lesions, although the whole body scan disclosed uptake at the second lumbar vertebra and rib. The patient refused further treatment.

  13. Discovering Biomarkers within the Genomic Landscape of Renal Cell Carcinoma

    PubMed Central

    A, Sankin

    2016-01-01

    Recent advances in molecular sequencing technology have led to the discovery of numerous biomarkers in renal cell carcinoma (RCC). These biomarkers have the potential to predict clinical outcomes and aid in clinical management decisions. The following commentary is a review of the preliminary data on some of the most promising genetic biomarker candidates. PMID:27104219

  14. Discovering Biomarkers within the Genomic Landscape of Renal Cell Carcinoma.

    PubMed

    A, Sankin

    2016-02-01

    Recent advances in molecular sequencing technology have led to the discovery of numerous biomarkers in renal cell carcinoma (RCC). These biomarkers have the potential to predict clinical outcomes and aid in clinical management decisions. The following commentary is a review of the preliminary data on some of the most promising genetic biomarker candidates.

  15. Cell deletion by apoptosis during regression of renal hyperplasia.

    PubMed Central

    Ledda-Columbano, G. M.; Columbano, A.; Coni, P.; Faa, G.; Pani, P.

    1989-01-01

    Regression of renal hyperplasia after withdrawal of the mitogenic stimulus induced by a single injection of lead nitrate was studied in male Wistar rats. Lead nitrate administration (10 mumol/100 g body weight) resulted in a ninefold increase in the incorporation of labeled thymidine into renal DNA and in an enhancement in the mitotic index; these changes were accompanied by an increase in the organ weight and DNA content that reached a maximum at 2 days. Regression of the renal hyperplasia was observed as early as 3 days after treatment and was completed within 2 weeks. Although lytic necrosis was not responsible for cell loss, the elimination of the excess renal cells took the form of apoptosis. This distinctive mode of cell death, which has been implicated in the involution of hyperplasia in other tissues and organs, was characterized by the occurrence of intracellular and extracellular membrane-bounded eosinophilic globules that often contained nuclear fragments. It affected mainly cells of the proximal tubules, and it was not detected once the kidney had regressed to its original mass. These results support the hypothesis that apoptosis is involved in the regulation of organ size. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2552812

  16. Prognostic factors for survival in metastatic renal cell carcinoma: update 2008.

    PubMed

    Bukowski, Ronald M

    2009-05-15

    A variety of prognostic factor models to predict survival in patients with metastatic renal cell carcinoma have been developed. Diverse populations of patients with variable treatments have been used for these analyses. A variety of clinical, pathologic, and molecular factors have been studied, but current models use predominantly easily obtained clinical factors. These approaches are reviewed, and current approaches to further refine and develop these techniques are reviewed.

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

    PubMed

    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.

  18. Comprehensive molecular characterization of clear cell renal cell carcinoma.

    PubMed

    2013-07-04

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.

  19. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

    PubMed Central

    2013-01-01

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (e.g. VHL) and the maintenance of chromatin states (e.g. PBRM1). We surveyed more than 400 tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/Akt pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving down-regulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, up-regulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 and GRB10. Remodeling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment. PMID:23792563

  20. The epigenetic landscape of clear-cell renal cell carcinoma

    PubMed Central

    Kluzek, Katarzyna; Bluyssen, Hans A

    2015-01-01

    Clear cell renal cell carcinoma (ccRCC) is the most common subtype of all kidney tumors. During the last few years, epigenetics has emerged as an important mechanism in ccRCC pathogenesis. Recent reports, involving large-scale methylation and sequencing analyses, have identified genes frequently inactivated by promoter methylation and recurrent mutations in genes encoding chromatin regulatory proteins. Interestingly, three of detected genes (PBRM1, SETD2 and BAP1) are located on chromosome 3p, near the VHL gene, inactivated in over 80% ccRCC cases. This suggests that 3p alterations are an essential part of ccRCC pathogenesis. Moreover, most of the proteins encoded by these genes cooperate in histone H3 modifications. The aim of this review is to summarize the latest discoveries shedding light on deregulation of chromatin machinery in ccRCC. Newly described ccRCC-specific epigenetic alterations could potentially serve as novel diagnostic and prognostic biomarkers and become an object of novel therapeutic strategies. PMID:28326264

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

    Cancer.gov

    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.

  2. A population approach to renal replacement therapy epidemiology: lessons from the EVEREST study.

    PubMed

    Caskey, Fergus J; Jager, Kitty J

    2014-08-01

    The marked variation that exists in renal replacement therapy (RRT) epidemiology between countries and within countries requires careful systematic examination if the root causes are to be understood. While individual patient-level studies are undoubtedly important, there is a complementary role for more population-level, area-based studies--an aetiological approach. The EVEREST Study adopted such an approach, bringing RRT incidence rates, survival and modality mix together with macroeconomic factors, general population factors and renal service organizational factors for up to 46 countries. This review considers the background to EVEREST, its key results and then the main methodological lessons and their potential application to ongoing work.

  3. Thulium laser supported nephron sparing surgery for renal cell carcinoma.

    PubMed

    Sciarra, Alessandro; Von Heland, Magnus; Minisola, Francesco; Salciccia, Stefano; Cattarino, Susanna; Gentile, Vincenzo

    2013-08-01

    We analyze the feasibility, advantages and results of the use of a thulium laser in nephron sparing surgery for renal cell carcinoma. In this single center prospective study 10 consecutive high risk patients underwent open or laparoscopic thulium laser assisted enucleation for small peripheral renal cell carcinoma at our department. We used a 2.0 μm continuous or pulsed thulium laser. This diode pumped solid state laser emits a wavelength of 2,013 nm in the infrared spectrum and penetrates tissue to a depth of 0.5 mm. The entire tumor enucleation was performed using the frontal thulium laser fiber. In all cases the thulium laser produced a smooth incision of the renal parenchyma and a safe delineation of the plane between the tumor and the surrounding tissue. In addition, in the off clamp procedures bleeding was limited during the dissection and did not interfere with the definition of the surgical plane. Median surgical time from the beginning of the laser assisted tumor dissection to the end, after verification of bleeding control on the cut surface, was 15 minutes (range 12 to 20). No significant (less than 40 cc) blood loss occurred during the laser assisted tumor dissection. All cases were clear cell renal cell carcinoma and no positive surgical margins were found. In all cases postoperative management was uncomplicated without evidence of hemorrhage. In our prospective preliminary experience, thulium laser assisted enucleation for renal cell carcinoma is a feasible, safe and effective procedure. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    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 < 0.033). Increased T1 signal intensity suggestive of hemorrhage was significantly more prevalent in RCC (p = 0.02). Interreader agreement for the subjective features ranged from 61.7% to 98.3%. In addition to various qualitative MRI parameters, normalized

  5. Graded activation of the MEK1/MT1-MMP axis determines renal epithelial cell tumor phenotype

    PubMed Central

    Mahimkar, Rajeev; Alfonso-Jaume, Maria Alejandra; Cape, Leslie M.; Dahiya, Rajvir; Lovett, David H.

    2011-01-01

    Activation of Raf/Ras/mitogen-activated protein kinase (MEK)/mitogen-activated protein kinase signaling and elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) are associated with von Hippel–Lindau gene alterations in renal cell carcinoma. We postulated that the degree of MEK activation was related to graded expression of MT1-MMP and the resultant phenotype of renal epithelial tumors. Madin Darby canine kidney epithelial cells transfected with a MEK1 expression plasmid yielded populations with morphologic phenotypes ranging from epithelial, mixed epithelial/mesenchymal to mesenchymal. Clones were analyzed for MEK1 activity, MT1-MMP expression and extent of epithelial–mesenchymal transition. Phenotypes of the MDCK-MEK1 clones were evaluated in vivo with nu/nu mice. Tissue microarray of renal cell cancers was quantitatively assessed for expression of phosphorylated MEK1 and MT1-MMP proteins and correlations drawn to Fuhrman nuclear grade. Graded increases in the MEK signaling module were associated with graded induction of epithelial–mesenchymal transition of the MDCK cells and induction of MT1-MMP transcription and synthesis. Inhibition of MEK1 and MT1-MMP activity reversed the epithelial–mesenchymal transition. Tumors generated by epithelial, mixed epithelial/mesenchymal and mesenchymal MDCK clones demonstrated a gradient of phenotypes extending from well-differentiated, fully encapsulated non-invasive tumors to tumors with an anaplastic morphology, high Fuhrman nuclear score, neoangiogenesis and invasion. Tumor microarray demonstrated a statistically significant association between the extent of phosphorylated MEK1, MT1-MMP expression and nuclear grade. We conclude that graded increases in the MEK1 signaling module are correlated with M1-MMP expression, renal epithelial cell tumor phenotype, invasive activity and nuclear grade. Phosphorylated MEK1 and MT1-MMP may represent novel, and mechanistic, biomarkers for the assessment of renal

  6. Graded activation of the MEK1/MT1-MMP axis determines renal epithelial cell tumor phenotype.

    PubMed

    Mahimkar, Rajeev; Alfonso-Jaume, Maria Alejandra; Cape, Leslie M; Dahiya, Rajvir; Lovett, David H

    2011-12-01

    Activation of Raf/Ras/mitogen-activated protein kinase (MEK)/mitogen-activated protein kinase signaling and elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) are associated with von Hippel-Lindau gene alterations in renal cell carcinoma. We postulated that the degree of MEK activation was related to graded expression of MT1-MMP and the resultant phenotype of renal epithelial tumors. Madin Darby canine kidney epithelial cells transfected with a MEK1 expression plasmid yielded populations with morphologic phenotypes ranging from epithelial, mixed epithelial/mesenchymal to mesenchymal. Clones were analyzed for MEK1 activity, MT1-MMP expression and extent of epithelial-mesenchymal transition. Phenotypes of the MDCK-MEK1 clones were evaluated in vivo with nu/nu mice. Tissue microarray of renal cell cancers was quantitatively assessed for expression of phosphorylated MEK1 and MT1-MMP proteins and correlations drawn to Fuhrman nuclear grade. Graded increases in the MEK signaling module were associated with graded induction of epithelial-mesenchymal transition of the MDCK cells and induction of MT1-MMP transcription and synthesis. Inhibition of MEK1 and MT1-MMP activity reversed the epithelial-mesenchymal transition. Tumors generated by epithelial, mixed epithelial/mesenchymal and mesenchymal MDCK clones demonstrated a gradient of phenotypes extending from well-differentiated, fully encapsulated non-invasive tumors to tumors with an anaplastic morphology, high Fuhrman nuclear score, neoangiogenesis and invasion. Tumor microarray demonstrated a statistically significant association between the extent of phosphorylated MEK1, MT1-MMP expression and nuclear grade. We conclude that graded increases in the MEK1 signaling module are correlated with M1-MMP expression, renal epithelial cell tumor phenotype, invasive activity and nuclear grade. Phosphorylated MEK1 and MT1-MMP may represent novel, and mechanistic, biomarkers for the assessment of renal cell

  7. iPS cell technology: Future impact on renal care.

    PubMed

    Freedman, Benjamin S; Steinman, Theodore I

    2015-08-01

    iPS cells from patients with kidney disease are a new tool with the potential to impact the future of renal care. They can be used in the laboratory to model the pathophysiology of human kidney disease, and have the potential to establish a new area of immunocompatible, on-demand renal transplantation. Critical challenges remain before the full potential of these cells can be accurately assessed. We need to understand whether the derived cell types are mature and can replace kidney function(s). To what extent can iPS cells model kidney disease in the simplified environment of cell culture? Ultimately, successful integration of these cells as autograft therapies will require demonstration of safety and efficacy equal or superior to the existing gold standards of kidney allograft transplantation and dialysis. Specific educational and infrastructural changes will be necessary if these specialized technologies are to be adopted as an accepted modalities in clinical medicine. Given these barriers, the first fruit of these labors is likely to be improved understanding of pathophysiological pathways in human IPS cell disease models, followed by drug discovery and testing. These experiments will lead naturally to improvements in differentiation and experiments in animal models testing function. The time course to achieve the desired goals remains unknown, but the ultimate hope is that new, more effective and less expensive modalities for renal replacement therapy will occur in the foreseeable future. A new standard of care for patients is anticipated that addresses limitations of currently available treatments.

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

    PubMed

    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.

    PubMed

    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. Sex Differences in Renal Proximal Tubular Cell Homeostasis.

    PubMed

    Seppi, Thomas; Prajczer, Sinikka; Dörler, Maria-Magdalena; Eiter, Oliver; Hekl, Daniel; Nevinny-Stickel, Meinhard; Skvortsova, Iraida; Gstraunthaler, Gerhard; Lukas, Peter; Lechner, Judith

    2016-10-01

    Studies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase-α Additionally, we quantified urinary excretion of blood plasma proteins α1-microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase-α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1-microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ-derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.

  11. Expression of Von Hippel – Lindau (VHL) gene mutation in diagnosed cases of renal cell carcinoma

    PubMed Central

    Shahzad, Humera; Kehar, Shahnaz Imdad; Ali, Shahzad; Tariq, Naila

    2014-01-01

    Objective: To evaluate the expression of Von Hippel Lindau (VHL) gene in diagnosed cases of renal cell carcinoma. Methods: This cross sectional study was conducted in department of Pathology, Basic Medical Sciences Institute, JPMC, Karachi, from January 2007 to December 2012. Paraffin embedded blocks of 30 cases of radical nephrectomy specimens diagnosed as renal cell carcinoma including CCRCC 21 (70%) CCPRCC, 3 (10%), PRCC 2 (6.79%), hybrid tumor 4 (13.3%), chromophobe tumor (0%) processed for VHL gene expression on Polymerase Chain Reaction. Results: All the 30 cases previously diagnosed as renal cell carcinoma were processed on PCR, VHL gene mutations were seen in 20 (95.23%) of CCRCC while a single case was negative for VHL mutations. All CCPRCC were negative for VHL mutation. Among the hybrid tumor 03 cases with foci of clear cells show VHL mutation while a single case showing combination of clear cells and chromophobe cells was negative for mutation. Both the cases of PRCC were positive for mutation. Exon 3 mutation at base pair 194 seen in 8 (32%) cases and Exon 2 mutation at base pair 150-159 seen in 17 (68%) cases. None of the cases showed Exon 1 mutation. Conclusion: The present study shows that majority of CCRCC showed VHL mutation including the hybrid tumor with clear cell component in our population. PMID:25097537

  12. Key role for CD4 T cells during mixed antibody mediated rejection of renal allografts

    PubMed Central

    Gaughan, A.; Wang, J.; Pelletier, R.P.; Nadasdy, T.; Brodsky, S.; Roy, S.; Lodder, M.; Bobek, D.; Mofatt-Bruce, S.; Fairchild, R.L.; Henry, M.L.; Hadley, G.A.

    2014-01-01

    We utilized mouse models to elucidate the immunologic mechanisms of functional graft loss during mixed antibody mediated rejection of renal allografts (mixed AMR), in which humoral and cellular responses to the graft occur concomitantly. Although the majority of T cells in the graft at the time of rejection were CD8 T cells with only a minor population of CD4 T cells, depletion of CD4 but not CD8 cells prevented acute graft loss during mixed AMR. CD4 depletion eliminated anti-donor alloantibodies and conferred protection from destruction of renal allografts. ELISPOT revealed that CD4 T effectors responded to donor alloantigens by both the direct and indirect pathways of allorecognition. In transfer studies, CD4 T effectors primed to donor alloantigens were highly effective at promoting acute graft dysfunction, and exhibited the attributes of effector T cells. Laser capture microdissection and confirmatory immunostaining studies revealed that CD4 T cells infiltrating the graft produced effector molecules with graft destructive potential. Bioluminescent imaging confirmed that CD4 T effectors traffic to the graft site in immune replete hosts. These data document that host CD4 T cells can promote acute dysfunction of renal allografts by directly mediating graft injury in addition to facilitating anti-donor alloantibody responses. PMID:24410909

  13. Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development

    SciTech Connect

    Nishikawa, Masaki; Yanagawa, Naomi; Kojima, Nobuhiko; Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto

    2012-01-13

    effective in inducing MM and UB markers, respectively. We also observed the emergence and gradual increase of cell populations expressing progenitor cell marker CD24 from Stage I to Stage III. These CD24{sup +} cells correlated with higher levels of expression of Brachyury at stage I, Pax2 and Lim1 at stage II and MM markers, such as WT1 and Cadherin 11, after exposure to UB-conditioned media at stage III. In conclusion, our results show that stepwise induction by tracing in vivo developmental stages was effective to generate renal lineage progenitor cells from mESC, and CD24 may serve as a useful surface marker for renal lineage cells at stage II and MM cells at stage III.

  14. Intravenous Renal Cell Transplantation for Polycystic Kidney Disease

    DTIC Science & Technology

    2014-06-01

    to measure serum creatinine. 5b. urine collection twice each month for measurements of protein and creatinine ratios Task 6. Intravital imaging ...information on the renal function, GFR and blood flow. In addition static CT images were obtained to measure kidney and cyst volumes. The CT scans were... images from kidneys stained for SAA (red) show GFP+ cells in kidneys from rats that received control (A) cells. SAA co-localizes with GFP (resulting

  15. Human Kidney-Derived Cells Ameliorate Acute Kidney Injury Without Engrafting into Renal Tissue.

    PubMed

    Santeramo, Ilaria; Herrera Perez, Zeneida; Illera, Ana; Taylor, Arthur; Kenny, Simon; Murray, Patricia; Wilm, Bettina; Gretz, Norbert

    2017-04-04

    Previous studies have suggested that CD133(+) cells isolated from human kidney biopsies have the potential to ameliorate injury following intravenous (IV) administration in rodent models of kidney disease by integrating into damaged renal tissue and generating specialized renal cells. However, whether renal engraftment of CD133(+) cells is a prerequisite for ameliorating injury has not yet been unequivocally resolved. Here, we have established a cisplatin-induced nephropathy model in immunodeficient rats to assess the efficacy of CD133(+) human kidney cells in restoring renal health, and to determine the fate of these cells after systemic administration. Specifically, following IV administration, we evaluated the impact of the CD133(+) cells on renal function by undertaking longitudinal measurements of the glomerular filtration rate using a novel transcutaneous device. Using histological assays, we assessed whether the human kidney cells could promote renal regeneration, and if this was related to their ability to integrate into the damaged kidneys. Our results show that both CD133(+) and CD133(-) cells improve renal function and promote renal regeneration to a similar degree. However, this was not associated with engraftment of the cells into the kidneys. Instead, after IV administration, both cell types were exclusively located in the lungs, and had disappeared by 24 hours. Our data therefore indicate that renal repair is not mediated by CD133(+) cells homing to the kidneys and generating specialized renal cells. Instead, renal repair is likely to be mediated by paracrine or endocrine factors. © Stem Cells Translational Medicine 2017.

  16. hTERT alone immortalizes epithelial cells of renal proximal tubules without changing their functional characteristics.

    PubMed

    Wieser, Matthias; Stadler, Guido; Jennings, Paul; Streubel, Berthold; Pfaller, Walter; Ambros, Peter; Riedl, Claus; Katinger, Hermann; Grillari, Johannes; Grillari-Voglauer, Regina

    2008-11-01

    Telomere-dependent replicative senescence is one of the mechanisms that limit the number of population doublings of normal human cells. By overexpression of telomerase, cells of various origins have been successfully immortalized without changing the phenotype. While a limited number of telomerase-immortalized cells of epithelial origin are available, none of renal origin has been reported so far. Here we have established simple and safe conditions that allow serial passaging of renal proximal tubule epithelial cells (RPTECs) until entry into telomere-dependent replicative senescence. As reported for other cells, senescence of RPTECs is characterized by arrest in G1 phase, shortened telomeres, staining for senescence-associated beta-galactosidase, and accumulation of gamma-H2AX foci. Furthermore, ectopic expression of the catalytic subunit of telomerase (TERT) was sufficient to immortalize these cells. Characterization of immortalized RPTEC/TERT1 cells shows characteristic morphological and functional properties like formation of tight junctions and domes, expression of aminopeptidase N, cAMP induction by parathyroid hormone, sodium-dependent phosphate uptake, and the megalin/cubilin transport system. No genomic instability within up to 90 population doublings has been observed. Therefore, these cells are proposed as a valuable model system not only for cell biology but also for toxicology, drug screening, biogerontology, as well as tissue engineering approaches.

  17. Omi/HtrA2 protease mediates cisplatin-induced cell death in renal cells.

    PubMed

    Cilenti, Lucia; Kyriazis, George A; Soundarapandian, Mangala M; Stratico, Valerie; Yerkes, Adam; Park, Kwon Moo; Sheridan, Alice M; Alnemri, Emad S; Bonventre, Joseph V; Zervos, Antonis S

    2005-02-01

    Omi/HtrA2 is a mitochondrial proapoptotic serine protease that is able to induce both caspase-dependent and caspase-independent cell death. After apoptotic stimuli, Omi is released to the cytoplasm where it binds and cleaves inhibitor of apoptosis proteins. In this report, we investigated the role of Omi in renal cell death following cisplatin treatment. Using primary mouse proximal tubule cells, as well as established renal cell lines, we show that the level of Omi protein is upregulated after treatment with cisplatin. This upregulation is followed by the release of Omi from mitochondria to the cytoplasm and degradation of XIAP. Reducing the endogenous level of Omi protein using RNA interference renders renal cells resistant to cisplatin-induced cell death. Furthermore, we show that the proteolytic activity of Omi is necessary and essential for cisplatin-induced cell death in this system. When renal cells are treated with Omi's specific inhibitor, ucf-101, they become significantly resistant to cisplatin-induced cell death. Ucf-101 was also able to minimize cisplatin-induced nephrotoxic injury in animals. Our results demonstrate that Omi is a major mediator of cisplatin-induced cell death in renal cells and suggest a way to limit renal injury by specifically inhibiting its proteolytic activity.

  18. Intratumoral morphologic and molecular heterogeneity of rhabdoid renal cell carcinoma: challenges for personalized therapy.

    PubMed

    Singh, Rajesh R; Murugan, Paari; Patel, Lalit R; Voicu, Horatiu; Yoo, Suk-Young; Majewski, Tadeusz; Mehrotra, Meenakshi; Wani, Khalida; Tannir, Nizar; Karam, Jose A; Jonasch, Eric; Wood, Christopher G; Creighton, Chad J; Medeiros, L Jeffrey; Broaddus, Russell R; Tamboli, Pheroze; Baggerly, Keith A; Aldape, Kenneth D; Czerniak, Bogdan; Luthra, Rajyalakshmi; Sircar, Kanishka

    2015-09-01

    Rhabdoid histology in clear-cell renal cell carcinoma is associated with a poor prognosis. The prognosis of patients with clear-cell renal cell carcinoma may also be influenced by molecular alterations. The aim of this study was to evaluate the association between histologic features and salient molecular changes in rhabdoid clear-cell renal cell carcinoma. We macrodissected the rhabdoid and clear-cell epithelioid components from 12 cases of rhabdoid clear-cell renal cell carcinoma. We assessed cancer-related mutations from eight cases using a clinical next-generation exome-sequencing platform. The transcriptome of rhabdoid clear-cell renal cell carcinoma (n=8) and non-rhabdoid clear-cell renal cell carcinoma (n=37) was assessed by RNA-seq and gene expression microarray. VHL (63%) showed identical mutations in all regions from the same tumor. BAP1 (38%) and PBRM1 (13%) mutations were identified in the rhabdoid but not in the epithelioid component and were mutually exclusive in 3/3 cases and 1 case, respectively. SETD2 (63%) mutations were discordant between different histologic regions in 2/5 cases, with mutations called only in the epithelioid and rhabdoid components, respectively. The transcriptome of rhabdoid clear-cell renal cell carcinoma was distinct from advanced-stage and high-grade clear-cell renal cell carcinoma. The diverse histologic components of rhabdoid clear-cell renal cell carcinoma, however, showed a similar transcriptomic program, including a similar prognostic gene expression signature. Rhabdoid clear-cell renal cell carcinoma is transcriptomically distinct and shows a high rate of SETD2 and BAP1 mutations and a low rate of PBRM1 mutations. Driver mutations in clear-cell renal cell carcinoma are often discordant across different morphologic regions, whereas the gene expression program is relatively stable. Molecular profiling of clear-cell renal cell carcinoma may improve by assessing for gene expression and sampling tumor foci from different

  19. Intratumoral Morphologic and Molecular Heterogeneity of Rhabdoid Renal Cell Carcinoma: Challenges for Personalized Therapy

    PubMed Central

    Singh, Rajesh R.; Murugan, Paari; Patel, Lalit R.; Voicu, Horatiu; Yoo, Suk-Young; Majewski, Tadeusz; Mehrotra, Meenakshi; Wani, Khalida; Tannir, Nizar; Karam, Jose A.; Jonasch, Eric; Wood, Christopher G.; Creighton, Chad J.; Medeiros, L. Jeffrey; Broaddus, Russell R.; Tamboli, Pheroze; Baggerly, Keith A.; Aldape, Kenneth D.; Czerniak, Bogdan; Luthra, Rajyalakshmi; Sircar, Kanishka

    2015-01-01

    Rhabdoid histology in clear cell renal cell carcinoma is associated with a poor prognosis. The prognosis of patients with clear cell renal cell carcinoma may also be influenced by molecular alterations. The aim of this study was to evaluate the association between histologic features and salient molecular changes in rhabdoid clear cell renal cell carcinoma. We macrodissected the rhabdoid and clear cell epithelioid components from 12 cases of rhabdoid clear cell renal cell carcinoma. We assessed cancer related mutations from 8 cases using a clinical next generation exome sequencing platform. The transcriptome of rhabdoid clear cell renal cell carcinoma (n=8) and non-rhabdoid clear cell renal cell carcinoma (n=37) was assessed by RNA-seq and gene expression microarray. VHL (63%) showed identical mutations in all regions from the same tumor. BAP1 (38%) and PBRM1 (13%) mutations were identified in the rhabdoid but not the epithelioid component and were mutually exclusive in 3/3 cases and 1 case, respectively. SETD2 (63%) mutations were discordant between different histologic regions in 2/5 cases, with mutations called only in the epithelioid and rhabdoid components, respectively. The transcriptome of rhabdoid clear cell renal cell carcinoma was distinct from advanced stage and high grade clear cell renal cell carcinoma. The diverse histologic components of rhabdoid clear cell renal cell carcinoma, however, showed a similar transcriptomic program, including a similar prognostic gene expression signature. Rhabdoid clear cell renal cell carcinoma is transcriptomically distinct and shows a high rate of SETD2 and BAP1 mutations and a low rate of PBRM1 mutations. Driver mutations in clear cell renal cell carcinoma are often discordant across different morphologic regions whereas the gene expression program is relatively stable. Molecular profiling of clear cell renal cell carcinoma may improve by assessing for gene expression and sampling tumor foci from different histologic

  20. Molecular aspects of renal cell carcinoma: a review

    PubMed Central

    Koul, Hari; Huh, Jung-Sik; Rove, Kyle O; Crompton, Luiza; Koul, Sweaty; Meacham, Randall B; Kim, Fernando J

    2011-01-01

    Renal cell carcinoma (RCC) is a disease in which cancer cells form in the tubules of the kidney. RCC, the incidence of which is increasing annually, represents five percent of adult epithelial cancers. Clear cell carcinoma represents the most frequent histological subtype. RCC is characterized by a lack of early warning signs, diverse clinical manifestations. Incidentally detected tumors in asymptomatic individuals have been steadily increasing owing to the increased usage of various imaging technologies. Currently there are no recommendations for screening to detect and make an early diagnosis of renal cancer. But in recent years, the discovery of new molecular and cytogenetic markers has led to the recognition and classification of several novel subtypes of RCC, and the introduction of molecular-targeted therapy for advanced-stage RCC. We performed a literature review using PubMed and discuss current knowledge of epidemiology, pathophysiology, evaluation, treatment, and future research directions of RCC. PMID:21969126

  1. FOXM1 participates in PLK1-regulated cell cycle progression in renal cell cancer cells

    PubMed Central

    ZHANG, ZHE; ZHANG, GUOJUN; KONG, CHUIZE

    2016-01-01

    The regulation of entry into and progression through mitosis is important for cell proliferation. Polo-like kinase 1 (PLK1) is involved in multiple stages of mitosis. Forkhead box protein M1 (FOXM1) has multiple functions in tumorigenesis and, in elevated levels, is frequently associated with cancer progression. The present study reports that FOXM1, a substrate of PLK1, controls the transcription mechanism that mediates the PLK1-dependent regulation of the cell cycle. The present study investigated the expression of PLK1 and FOXM1 in the clear renal cell carcinoma 769-P and ACHN cell lines, and indicated that the expression of PLK1 and FOXM1 are correlated in human renal cell cancer cell lines and that the suppression of PLK1 may decrease the expression of FOXM1. The knockdown of FOXM1 or PLK1 in renal cell cancer cell lines caused cell cycle progression to be blocked. As a result, the present study indicated the involvement of FOXM1 in PLK1-regulated cell cycle progression. PMID:27073539

  2. TERT promoter mutations in clear cell renal cell carcinoma.

    PubMed

    Hosen, Ismail; Rachakonda, P Sivaramakrishna; Heidenreich, Barbara; Sitaram, Raviprakash T; Ljungberg, Börje; Roos, Göran; Hemminki, Kari; Kumar, Rajiv

    2015-05-15

    We screened promoter region of the telomerase reverse transcriptase (TERT) for activating somatic mutations in 188 tumors from patients with clear cell renal cell carcinoma (ccRCC). Twelve tumors (6.4%) carried a mutation within the core promoter region of the gene. The mutations were less frequent in high grade tumors compared to low grade tumors [odds ratio (OR) = 0.15, 95% confidence interval (CI) = 0.03-0.72, p = 0.02]. Multivariate analysis for cause specific survival showed statistically significant poor outcome in patients with TERT promoter mutations [hazard ratio (HR) = 2.90, 95% CI = 1.13-7.39, p = 0.03]. A common polymorphism (rs2853669) within the locus seemed to act as a modifier of the effect of the mutations on patient survival as the noncarriers of the variant allele with the TERT promoter mutations showed worst survival (HR = 3.34, 95% CI = 1.24-8.98, p = 0.02). We also measured relative telomere length (RTL) in tumors and difference between tumors with and without the TERT promoter mutations was not statistically significant. Similarly, no difference in patient survival based on RTL in tumors was observed. Our study showed a relatively low frequency of TERT promoter mutations in ccRCC. Nevertheless, patients with the mutations, particularly in the absence of the rs2853669 variant showed the worst disease-specific survival. Thus, it is possible that the TERT promoter mutations define a small subset of tumors with an aggressive behavior. © 2014 UICC.

  3. Progesterone receptor reactivity in renal oncocytoma and chromophobe renal cell carcinoma.

    PubMed

    Mai, K T; Teo, I; Belanger, E C; Robertson, S J; Marginean, E C; Islam, S

    2008-02-01

    To investigate the reactivity for oestrogen and progesterone receptors (ER and PR) in renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). Thirty-eight RO, 25 CHRCC, 20 papillary RCC with oncocytic cytoplasm and 10 clear cell RCC with dominant eosinophilic cytoplasm were submitted for immunohistochemistry for ER, PR, CD117 and RCC. All cases of RO and CHRCC displayed moderately positive reactivity for PR. The nuclear reactivity ranged from 60% to 90% in RO and from occasional cells to 70% in CHRCC. In CHRCC, reactivity tended to be more prevalent in areas of tumour cells with eosinophilic cytoplasm. Progesterone reactivity was focal in areas. All RO and most CHRCC were reactive for CD117 and neither RO nor CHRCC was reactive for RCC. CD117 reactivity tended to be more intense in CHRCC than in RO. Negative reactivity for CD117 and positive reactivity for RCC were observed in almost all RCC, as reported in the literature. PR can be used in combination with CD117 and RCC in the differential diagnosis of RO and eosinophilic variant of CHRCC with other RCC with oncocytic or eosinophilic cytoplasm.

  4. Benign and tumor parenchyma metabolomic profiles affect compensatory renal growth in renal cell carcinoma surgical patients

    PubMed Central

    Rubinstein, Nimrod D.; Reznik, Ed; Shingarev, Roman; Juluru, Krishna; Akin, Oguz; Hsieh, James J.; Jaimes, Edgar A.; Russo, Paul; Susztak, Katalin; Coleman, Jonathan A.; Hakimi, A. Ari

    2017-01-01

    Background and objectives Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. Design, setting, participants, and measurements Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG. Contra-lateral kidney volume fold-change within a 3.3 +/- 2.1 years follow-up interval was used as a surrogate for long-term CRG. Using a multivariable statistical model, we identified metabolites whose abundances significantly associate with CRG. Results Our analysis found 13 metabolites in the benign (e.g. L-urobilin, Variable Influence in Projection, VIP, score = 3.02, adjusted p = 0.017) and 163 metabolites in the malignant (e.g. 3-indoxyl-sulfate, VIP score = 1.3, adjusted p = 0.044) tissues that significantly associate with CRG. Benign/tumor fold change in metabolite abundances revealed three additional metabolites with that significantly positively associate with CRG (e.g. p-cresol sulfate, VIP score = 2.945, adjusted p = 0.033). At the pathway level, we show that fatty-acid oxidation is highly enriched with metabolites whose benign tissue abundances strongly positively associate with CRG, both pre-operatively and long term, whereas in the tumor tissue significant enrichment of dipeptides and benzoate (positive association), glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways, were observed. Conclusion These data suggest that specific biological processes in the benign as well as in the tumor parenchyma strongly influence compensatory renal growth. PMID

  5. c-Met in chromophobe renal cell carcinoma.

    PubMed

    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.

  6. Axitinib in sequential therapy in metastatic renal cell carcinoma

    PubMed Central

    Hryciuk, Beata; Stec, Rafał; Mączewski, Michał; Szczylik, Cezary

    2016-01-01

    Efficacy of new molecularly targeted drugs in the treatment of renal cell carcinoma (RCC), confirmed in clinical studies in relation to survival and prolongation of time to progression, has became a big chance for patients with metastatic renal cell cancer. Axitinib is a potent and selective receptor tyrosine kinase for vascular endothelial growth factor (VEGFR-1, -2, -3), platelet-derived growth factor β (PDGRF-β) and c-KIT. This is a case report of a 57-year old female patient with a history of left nephrectomy due to clear cell renal cell carcinoma. The patient had received three prior systemic treatments (interferon – sorafenib – everolimus). After consecutive progression the patient was qualified to 4th line therapy – axitinib at a dose of 5 mg twice daily. Partial response to treatment was achieved. After 6 months therapy was stopped due to the disease progression. The total time to progression was 37.5 months. The total survival time from the disease diagnosis was 45 months. Based on literature date and own experience we showed that sequential treatment RCC is associated with improved survival. In summary, axitinib may be an effective drug after failure of tyrosine-kinase inhibitor (TKI) therapy in previous lines of therapy.

  7. Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus.

    PubMed

    Cheng, Dong; Zhao, Jiangtao; Jian, Liguo; Ding, Tongbin; Liu, Shichao

    2016-09-01

    Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 ± 0.9 vs.12.5 ± 0.6, p < 0.001). The red cell distribution width was positively associated with albuminuria creatinine ratio (r = 0.567, p < 0.001). Multiple logistic regressions showed that red cell distribution width was still associated with early-stage renal injury after adjusting for many other potential cofounders. Compared with the first quartile, the risk ratio of the second, the third and the fourth quartile were 1.38 (95%CI: 1.06-1.80), 1.57 (95%CI: 1.21-2.97), 2.71 (95%CI: 2.08-3.54), respectively. Besides, systolic blood pressure, estimated glomerular filtration rate, uric acid and blood urea nitrogen were also significantly associated with renal injury in gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices.

  8. Targeted therapy for renal cell carcinoma: a new treatment paradigm

    PubMed Central

    2007-01-01

    Metastatic clear cell renal cell cancer has traditionally been treated with cytokines (interferon or interleukin-2). Improved understanding of biology has engendered novel targeted therapeutic agents that have altered the natural history of this disease. The vascular endothelial growth factor and its related receptor and the mTOR signal transduction pathway have particularly been exploited. Sunitinib malate, sorafenib tosylate, temsirolimus, and bevacizumab have improved clinical outcomes in randomized trials. Other multitargeted tyrosine kinase inhibitors (lapatinib, axitinib, pazopanib) and antiangiogenic agents (VEGF Trap, lenalidomide) have also demonstrated activity in early studies. Combinations of these agents are being evaluated. The future of the therapy of renal cancer appears promising owing to the efficacy of these novel agents. PMID:17637878

  9. Tubulocystic renal cell carcinoma: Report of a rare case

    PubMed Central

    Kakkar, Aanchal; Sharma, Mehar C.; Uppal, Manpreet; Chumber, Sunil

    2015-01-01

    Cystic neoplasms of the kidney are rare, and present a unique diagnostic challenge. We report the case of an elderly male who presented with a large cystic neoplasm, which was a diagnostic dilemma clinically and radiologically. Histopathological examination showed a tumour composed of variably sized tubules lined by atypical cells having large round nuclei with prominent nucleoli. Hobnailing was seen at places. Tumour cells were immunopositive for pancytokeratin, vimentin, CD10, CK19 and AMACR, confirming a diagnosis of tubulocystic renal cell carcinoma (TC-RCC). PMID:26425234

  10. Simulating Heterogeneous Tumor Cell Populations

    PubMed Central

    Bar-Sagi, Dafna; Mishra, Bud

    2016-01-01

    Certain tumor phenomena, like metabolic heterogeneity and local stable regions of chronic hypoxia, signify a tumor’s resistance to therapy. Although recent research has shed light on the intracellular mechanisms of cancer metabolic reprogramming, little is known about how tumors become metabolically heterogeneous or chronically hypoxic, namely the initial conditions and spatiotemporal dynamics that drive these cell population conditions. To study these aspects, we developed a minimal, spatially-resolved simulation framework for modeling tissue-scale mixed populations of cells based on diffusible particles the cells consume and release, the concentrations of which determine their behavior in arbitrarily complex ways, and on stochastic reproduction. We simulate cell populations that self-sort to facilitate metabolic symbiosis, that grow according to tumor-stroma signaling patterns, and that give rise to stable local regions of chronic hypoxia near blood vessels. We raise two novel questions in the context of these results: (1) How will two metabolically symbiotic cell subpopulations self-sort in the presence of glucose, oxygen, and lactate gradients? We observe a robust pattern of alternating striations. (2) What is the proper time scale to observe stable local regions of chronic hypoxia? We observe the stability is a function of the balance of three factors related to O2—diffusion rate, local vessel release rate, and viable and hypoxic tumor cell consumption rate. We anticipate our simulation framework will help researchers design better experiments and generate novel hypotheses to better understand dynamic, emergent whole-tumor behavior. PMID:28030620

  11. Bone pulsating metastasis due to renal cell carcinoma.

    PubMed

    Cınar, Murat; Derincek, Alihan; Karan, Belgin; Akpınar, Sercan; Tuncay, Cengiz

    2010-11-01

    Pulsation on the bone cortex surface is a rare condition. Pulsative palpation of the superficial-located bone tumors can be misperceived as an aneurysm. Fifty-eight-year-old man is presented with pulsating bone mass in his proximal tibia. During angiographic examination, hypervascular masses were diagnosed both at right kidney and at right proximal tibia. Renal cell carcinoma was diagnosed after abdominal CT scan. Proximal tibia biopsy was complicated with projectile bleeding.

  12. Thermal Protection during Percutaneous Thermal Ablation of Renal Cell Carcinoma

    PubMed Central

    Kam, Anthony W.; Littrup, Peter J.; Walther, McClellan M.; Hvizda, Julia; Wood, Bradford J.

    2008-01-01

    Thermal injury to collateral structures is a known complication of thermal ablation of tumors. The authors present the use of CO2 dissection and inserted balloons to protect the bowel during percutaneous radiofrequency (RF) ablation and cryotherapy of primary and locally recurrent renal cell carcinoma. These techniques offer the potential to increase the number of tumors that can be treated with RF ablation or cryotherapy from a percutaneous approach. PMID:15231890

  13. Malignant renal tumors in children

    PubMed Central

    Sanchez, Thomas Ray; Wootton-Gorges, Sandra

    2015-01-01

    Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. PMID:28326263

  14. RENAL CELL CARCINOMA METASTASIS TO THE SINONASAL CAVITY: CASE REPORT.

    PubMed

    Kovačić, Marijan; Krvavica, Ana; Rudić, Milan

    2015-06-01

    Renal cell carcinoma accounts for 3% of all adult malignant tumors. Common sites of metastases are lungs, bone, liver, brain and adrenal glands. Metastatic disease to the head and neck ranges from 15% to 30%. The 5-year survival rate after nephrectomy is 60%-75%, but with multiorgan metastases the 5-year survival rate is significantly lower, 0-7%. A case is presented of a female patient diagnosed with renal cell carcinoma metastases to the paranasal sinuses, diagnosed and treated at the Department of ENT and Head and Neck Surgery, Zadar General Hospital, Zadar, Croatia. The tumor was surgically removed. Unfortunately, the patient died one year after the procedure due to multiorgan failure. Although metastases of renal cell carcinoma to the head and neck are very rare, it should be first suspected when investigating a metastatic tumor in this region. Surgical excision offers the best hope for long term survival. In case of unresectable tumor, other treatment options should be considered such as radiotherapy, immunotherapy and chemotherapy.

  15. Renal cell carcinoma with vascular invasion: Mortality and prognostic factors.

    PubMed

    Rodríguez-Cabello, M A; Laso-García, I; Donis-Canet, F; Gómez-Dos-Santos, V; Varona-Crespo, C; Burgos-Revilla, F J

    2017-03-01

    Analysis of the results of patients who had been operated of renal cell carcinoma with vascular invasion in our institution, evaluation of prognostic factors and complications. Retrospective observational study of 37 patients diagnosed of renal cell carcinoma with vascular invasion operated between May 1999 and July 2013. We used the method of Kaplan-Meier survival analysis and the Mantel-Haenszel's test (log rank) and the Cox's proportional hazards analysis test to analyse the risk factors of mortality. The median age was 60 years. Mean follow-up period was 42.1 months. The median overall survival and disease-free survival were 53.8and 36.3 months, respectively. There was statistical association between overall survival and ASA (p=0.047), tumor stage (p=0.003), lymph node involvement (p=0.024), presence of metastases (p=0.013), level of tumor thrombus (p=0, 05) and histological type (p=0.001). 14 patients had grade IIIb complications or higher according to the Clavien Dindo classification, the most frequent was bleeding. Renal cell carcinoma with vascular invasion is a disease with high rate of mortality. Surgery is a therapeutic option that can be curative. The number of complications is important. Survival is conditioned by the ASA, tumor stage, the level of tumor thrombus, lymph node involvement, metastasis and histological type. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin.

    PubMed

    Kobayashi, Hanako; Liu, Qingdu; Binns, Thomas C; Urrutia, Andres A; Davidoff, Olena; Kapitsinou, Pinelopi P; Pfaff, Andrew S; Olauson, Hannes; Wernerson, Annika; Fogo, Agnes B; Fong, Guo-Hua; Gross, Kenneth W; Haase, Volker H

    2016-05-02

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2-/- renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2-/- mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation.

  17. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

    PubMed Central

    Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

    2016-01-01

    Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

  18. Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

    PubMed

    Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

    2015-07-01

    Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p <0.001). A colony of circulating endothelial progenitor cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p <0.001). The culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p <0.001). The circulating endothelial progenitor cell level correlated positively with the number of patient colonies (r = 0.762, p <0.001). Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p <0.001). Earlier emergence of circulating endothelial progenitor cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results

  19. Renal cell carcinoma metastatic to the nasal cavity.

    PubMed

    Terada, Tadashi

    2012-01-01

    Metastatic renal cell carcinoma of the nasal cavity is very rare. A 76-year-old man presented with epistaxis and admitted to our hospital. His past histories were right radical nephrectomy for renal cell carcinomas at the age of 68 years and brain infarction at the age of 75 years. Laryngoscopic examination revealed a red polyp of the right nasal cavity. Imaging modalities including CT and MRI also revealed a tumor measuring 2 x 3 x 2 cm. Angiography showed that the tumor is very hypervascular. Clinical diagnosis was angiogenic tumors including hemangioma, sinonasal hemangiopericytoma, and paraganglioma. A blood data showed anemia and low platerets, and bone marrow biopsy revealed myelodysplastic syndrome. A coiling embolization of the feeding artery was performed, and the tumor reduced markedly. The tumor was resected almost entirely. Pathologically, the tumor was 2 x 1.5 x 1.5 cm red tumor. The tumor cells had clear cytoplasm, and arranged in a trabecular pattern lined by a layer of endothelial cells. Atypia is mild. Immunohistochemically, the tumor cells were positive for pancytokeratin (AE1/3, CAM5.2), RCC ma, CD10, and Ki-67 (labeling=20%), but negative for CD34, factor-VIII-related antigen, CEA, EMA, melanosome (HMB45), S100 protein, p53, and HepPar-1. The pathological diagnosis was made without knowledge of kidney status. A pathological diagnosis of metastatic renal cell carcinoma of clear cell type (grade 1) was made. The patient is now free from tumor, and palliative chemoradiation is considered.

  20. Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-α as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population

    PubMed Central

    Castellano, D.; del Muro, X. Garcia; Pérez-Gracia, J. L.; González-Larriba, J. L.; Abrio, M. V.; Ruiz, M. A.; Pardo, A.; Guzmán, C.; Cerezo, S. Díaz; Grande, E.

    2009-01-01

    Background: The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-α) treatment in patients with metastatic renal cell carcinoma (mRCC). Patients and methods: In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN-α (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included. Results: Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values. Conclusions: Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-α. PMID:19549706

  1. MiT family translocation renal cell carcinoma.

    PubMed

    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.

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

    SciTech Connect

    Okano, Kazuhiro 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.

  3. Calponin h1 expression in renal tumor vessels: correlations with multiple pathological factors of renal cell carcinoma.

    PubMed

    Islam, A H M Manjurul; Ehara, Takashi; Kato, Haruaki; Hayama, Masayoshi; Kobayashi, Shinya; Igawa, Yasuhiko; Nishizawa, Osamu

    2004-03-01

    We determined whether the architecture of renal tumor vessels is immunohistochemically different from that of normal renal vessels and related to the various pathological factors that affect prognosis of renal cell carcinoma (RCC). A total of 52 cases of primary RCC were selected. Tissues from radical nephrectomy specimens were stained with antibody to alpha-smooth muscle actin (alpha-SMA) and calponin h1. Immunostaining was evaluated semiqualitatively as 0-no staining to 3+-strong staining. Tumor cell proliferation was observed using proliferating marker Ki-67. Data were statistically compared with pathological factors, such as tumor size, histological pattern, growth pattern, cell type, nuclear grade, pathological stage and presence or absence of venous invasion. In normal renal tissues smooth muscle cells of the blood vessels showed strong immunoreactions with antibody to calponin h1 and alpha-SMA. Although alpha-SMA antibody showed similar strong immunoreactions in all types of renal tumor vessels, we observed qualitative alterations in the expression of calponin h1 in different types of RCCs. Strong to moderate immunoreactions with calponin h1 were observed in tumors with expansive growth and an alveolar pattern. Small tumors without venous invasion and chromophobe cell carcinomas also showed strong to moderate expression of calponin h1. Weak or absent expression of calponin h1 was observed significantly in infiltrating tumors, sarcomatous type, large, high grade and high stage tumors associated with significantly higher proliferating indexes. Our results strongly suggest that the renal tumor vessels are immunohistochemically different from normal renal vessels in respect to calponin h1 expression. We speculate that due to the decrease in or absence of calponin h1 tumor vessels do not develop adequate maturity to maintain vascular integrity. In addition, the distribution of calponin h1 significantly correlated with multiple pathological factors of RCC

  4. Urinary signatures of Renal Cell Carcinoma investigated by peptidomic approaches.

    PubMed

    Chinello, Clizia; Cazzaniga, Marta; De Sio, Gabriele; Smith, Andrew James; Gianazza, Erica; Grasso, Angelica; Rocco, Francesco; Signorini, Stefano; Grasso, Marco; Bosari, Silvano; Zoppis, Italo; Dakna, Mohammed; van der Burgt, Yuri E M; Mauri, Giancarlo; Magni, Fulvio

    2014-01-01

    Renal Cell Carcinoma (RCC) is typically asymptomatic and surgery usually increases patient's lifespan only for early stage tumours. Moreover, solid renal masses cannot be confidently differentiated from RCC. Therefore, markers to distinguish malignant kidney tumours and for their detection are needed. Two different peptide signatures were obtained by a MALDI-TOF profiling approach based on urine pre-purification by C8 magnetic beads. One cluster of 12 signals could differentiate malignant tumours (n = 137) from benign renal masses and controls (n = 153) with sensitivity of 76% and specificity of 87% in the validation set. A second cluster of 12 signals distinguished clear cell RCC (n = 118) from controls (n = 137) with sensitivity and specificity values of 84% and 91%, respectively. Most of the peptide signals used in the two models were observed at higher abundance in patient urines and could be identified as fragments of proteins involved in tumour pathogenesis and progression. Among them: the Meprin 1α with a pro-angiogenic activity, the Probable G-protein coupled receptor 162, belonging to the GPCRs family and known to be associated with several key functions in cancer, the Osteopontin that strongly correlates to tumour stages and invasiveness, the Phosphorylase b kinase regulatory subunit alpha and the SeCreted and TransMembrane protein 1.

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

    PubMed

    Muglia, Valdair F; Prando, Adilson

    2015-01-01

    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.

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

    PubMed Central

    Muglia, Valdair F.; Prando, Adilson

    2015-01-01

    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. PMID:26185343

  7. Transcatheter embolization of advanced renal cell carcinoma with radioactive seeds

    SciTech Connect

    Lang, E.K.; deKernion, J.B.

    1981-11-01

    Advanced renal cell carcinoma was treated by transcatheter embolization with radioactive seeds. There were 14 patients with nonresectable or metastatic disease (stage IV) and 8 with stage II tumors treated. In 8 patients the tumor was implanted with radon seeds, complemented by 2,500 rad of external beam therapy, and 10 were treated by embolization with 125iodine seeds. The total dose delivered ranged form 1,600 to 14,000 rad. Several patients also had intra-arterial chemotherapy. Survival was improved over previously reported studies: 13 of 22 (59 per cent) at risk for 2 years and 5 of 15 (33 per cent) for 5 years. Distant metastases did not resolve but significant local palliation was achieved. Tumor size decreased in all patients, 8 of whom subsequently underwent nephrectomy. Other local effects included pain control (10 per cent), weight gain (75 per cent) and control of hemorrhage (88 per cent). Toxicity was minimal and consisted of mild nausea or pain. This approach, using a low energy emitter, allows selective high dose radiation of the tumor, while sparing the adjacent normal tissues. In contrast to renal artery occlusion with inert embolic material, subsequent nephrectomy in patients with disseminated disease is not necessary. Transcatheter embolization with radioactive seeds should be considered a reasonable palliative procedure in patients with nonresectable primary renal cell carcinoma.

  8. Urinary Signatures of Renal Cell Carcinoma Investigated by Peptidomic Approaches

    PubMed Central

    De Sio, Gabriele; Smith, Andrew James; Gianazza, Erica; Grasso, Angelica; Rocco, Francesco; Signorini, Stefano; Grasso, Marco; Bosari, Silvano; Zoppis, Italo; Dakna, Mohammed; van der Burgt, Yuri E. M.; Mauri, Giancarlo; Magni, Fulvio

    2014-01-01

    Renal Cell Carcinoma (RCC) is typically asymptomatic and surgery usually increases patient's lifespan only for early stage tumours. Moreover, solid renal masses cannot be confidently differentiated from RCC. Therefore, markers to distinguish malignant kidney tumours and for their detection are needed. Two different peptide signatures were obtained by a MALDI-TOF profiling approach based on urine pre-purification by C8 magnetic beads. One cluster of 12 signals could differentiate malignant tumours (n = 137) from benign renal masses and controls (n = 153) with sensitivity of 76% and specificity of 87% in the validation set. A second cluster of 12 signals distinguished clear cell RCC (n = 118) from controls (n = 137) with sensitivity and specificity values of 84% and 91%, respectively. Most of the peptide signals used in the two models were observed at higher abundance in patient urines and could be identified as fragments of proteins involved in tumour pathogenesis and progression. Among them: the Meprin 1α with a pro-angiogenic activity, the Probable G-protein coupled receptor 162, belonging to the GPCRs family and known to be associated with several key functions in cancer, the Osteopontin that strongly correlates to tumour stages and invasiveness, the Phosphorylase b kinase regulatory subunit alpha and the SeCreted and TransMembrane protein 1. PMID:25202906

  9. Occupational Sunlight Exposure and Risk of Renal Cell Carcinoma

    PubMed Central

    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

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

    PubMed

    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.

  11. Role of partial nephrectomy as cytoreduction in the management of metastatic renal cell carcinoma.

    PubMed

    Karam, J A; Babaian, K N; Tannir, N M; Matin, S F; Wood, C G

    2015-06-01

    In this review, we describe the role, feasibility and safety of partial nephrectomy in the setting of metastatic renal cell carcinoma. Partial nephrectomy is currently the preferred therapeutic modality in patients with localized renal tumors, while radical cytoreductive nephrectomy is the standard of care for appropriately selected patients with metastatic disease. Several studies have shown the prognostic value of percentage tumor removed when cytoreductive nephrectomy is done. This concept of percentage tumor removal and the associated benefit should also be applied when considering patients for cytoreductive partial nephrectomy; however, the potential adverse events after partial nephrectomy should be kept in mind, as these, when they occur, could delay time to starting systemic therapy. Several small retrospective studies have shown the feasibility of this approach in carefully selected patient groups. In well-selected patients with metastatic disease and primary tumors that are amenable to nephron sparing approaches, partial nephrectomy could offer an alternative to radical nephrectomy, with manageable adverse events, and good renal functional outcomes. Preserving renal function in this population could allow these patients to participate in clinical trial that they otherwise might not qualify for.

  12. Demyelinating Peripheral Neuropathy Due to Renal Cell Carcinoma

    PubMed Central

    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

  13. Systemic treatment of renal cell cancer: A comprehensive review.

    PubMed

    Sánchez-Gastaldo, Amparo; Kempf, Emmanuelle; González Del Alba, Aránzazu; Duran, Ignacio

    2017-09-01

    Kidney cancer represents about 5% of all new cancer diagnoses. The most common form of kidney cancer arises from renal epithelium, named renal cell carcinoma (RCC). This entity comprises different histological and molecular subtypes. Unraveling the molecular biology and cytogenetic of RCC has enabled the development of several targeted agents that have improved treatment outcomes of these patients. This article reviews all the agents currently approved for the treatment of RCC, and discuss upcoming molecules. Mechanism of action, preclinical and clinical development and ongoing trials, are presented for each agent, providing a broad vision of the current state of targeted therapy in RCC and possible future developments. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. Renal cell carcinoma metastasis to the paranasal sinuses and orbit

    PubMed Central

    Evgeniou, Evgenios; Menon, Kavitha R; Jones, Graeme L; Whittet, Heiki; Williams, Wynne

    2012-01-01

    The authors report a rare case of renal cell carcinoma (RCC) metastasis to the paranasal sinuses. The authors review RCC and its potential for sinonasal metastasis and discuss the variable presentation and need for clinical suspicion for early diagnosis and treatment. A 74-year-old man presented with numbness of the left side of the face, reduced visual acuity and ptosis 12 years after nephrectomy for RCC. Imaging studies showed a lesion in the left pterygopalatine fossa and the histological features supported the diagnosis of metastatic RCC. RCC metastasis to the paranasal sinuses is very rare and can present with various symptoms depending on the affected organ. These symptoms occasionally are the initial manifestation of renal RCC and it is very important to recognise them so that the patient receives the appropriate therapy to improve survival. PMID:22605794

  15. Renal cell carcinoma metastasis to the paranasal sinuses and orbit.

    PubMed

    Evgeniou, Evgenios; Menon, Kavitha R; Jones, Graeme L; Whittet, Heiki; Williams, Wynne

    2012-03-27

    The authors report a rare case of renal cell carcinoma (RCC) metastasis to the paranasal sinuses. The authors review RCC and its potential for sinonasal metastasis and discuss the variable presentation and need for clinical suspicion for early diagnosis and treatment. A 74-year-old man presented with numbness of the left side of the face, reduced visual acuity and ptosis 12 years after nephrectomy for RCC. Imaging studies showed a lesion in the left pterygopalatine fossa and the histological features supported the diagnosis of metastatic RCC. RCC metastasis to the paranasal sinuses is very rare and can present with various symptoms depending on the affected organ. These symptoms occasionally are the initial manifestation of renal RCC and it is very important to recognise them so that the patient receives the appropriate therapy to improve survival.

  16. Chromophobe renal cell carcinoma in a pediatric living-related kidney transplant recipient.

    PubMed

    Greco, Andres J; Baluarte, Jorge H; Meyers, Kevin E C; Sellers, Marty T; Suchi, Mariko; Biegel, Jaclyn A; Kaplan, Bernard S

    2005-06-01

    Renal cell carcinoma can occur in children who have received renal allografts from adults. Chromophobe renal cell carcinoma is a rare variant of renal carcinoma with distinct histochemical, ultrastructural, and genetic characteristics. We describe the incidental finding of a chromophobe renal cell carcinoma in a 13 1/2-year-old boy 5 years after receiving a living-related renal transplant. This tumor was found by serendipity during the evaluation of fever and inguinal lymphadenopathy, with the presumptive diagnosis of posttransplantation lymphoproliferative disorder. The patient was found to have cat-scratch disease. A renal cell carcinoma should be considered in the differential diagnosis of a pediatric recipient of an adult kidney with an incidental finding of a tumor in the graft.

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

    EPA Science Inventory

    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. ...

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

    EPA Science Inventory

    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. ...

  19. Inhibition of γ-secretase by retinoic acid chalcone (RAC) induces G2/M arrest and triggers apoptosis in renal cell carcinoma

    PubMed Central

    Li, Qing-Chun; Li, Hong-Jun; Liu, Shi; Liang, Yun; Wang, Xue; Cui, Lei

    2015-01-01

    The present study was devised to investigate the effect of RAC on inhibition of cell proliferation and apoptosis of renal carcinoma cells. MTT assay and flow cytometry analysis were used to determine cell proliferation and apoptosis along with cell cycle examination. Western blot analysis and immunohistochemistry were used for the detection of expression levels of Notch1 and Jagged1 in renal cell carcinoma (RCC) and normal kidney tissues. The results revealed a significant inhibition of cell proliferation, G2/M phase cell cycle arrest and cell apoptosis at 30 μM concentration of RAC after 72 h. In ACHN and 769-P cells, the population in G2/M phase was increased to 45.27, and 54.23% respectively on treatment with 30 μM RAC for 72 h. In 769-P and ACHN renal carcinoma cells treatment with 30 μM RAC caused 69.71 and 59.27% of the cells to undergo apoptosis compared to 5.23 and 4.93% respectively in control cells. The positive staining rates of Notch1 and Jagged1 in renal carcinoma tissues were 95.3 and 93.0% compared to normal kidney tissues 36.4 and 42.4% respectively. Treatment of renal carcinoma tissues caused a significant decrease in staining rates of Notch1 and Jagged1 after 96 h. Thus RAC can be a potent agent in the treatment of renal cell carcinoma. PMID:26045747

  20. Has the yearly increase in the renal replacement therapy population ended?

    PubMed

    Rosansky, Steven Jay; Clark, William F

    2013-09-01

    The recent decline in the number of new patients undergoing dialysis and transplantation in the United States may be linked to a reduction in the incidence of early-start dialysis, defined as the initiation of renal replacement therapy (RRT) at an estimated GFR ≥10 ml/min per 1.73 m(2). We examined the most recent data from the U.S. Renal Data System to determine how this trend will affect the future incidence of ESRD in the United States. The percentage of early dialysis starts grew from 19% to 54% of all new starts between 1996 and 2009 but remained stable between 2009 and 2011. Similarly, the incident RRT population increased substantially in all age groups between 1996 and 2005, with the largest increase occurring in patients aged ≥75 years. Early dialysis starts accounted for most of the increase in the incident RRT population in all age groups during this time period, and between 2005 and 2010, the increase slowed dramatically. Although the future incident RRT population will be determined in part by population growth, these results suggest that later dialysis starts and greater use of conservative and palliative care, which may improve quality of life for elderly patients with advanced renal failure, will continue to attenuate the increase observed in previous years.

  1. Thyroid metastasis as initial presentation of clear cell renal carcinoma

    PubMed Central

    Ramírez-Plaza, César Pablo; Domínguez-López, Marta Elena; Blanco-Reina, Francisco

    2015-01-01

    Introduction Metastatic tumors account for 1.4–2.5% of thyroid malignancies. About 25–30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. Presentation of the case A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles “suggestive” of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. Discussion Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. Conclusion The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of “de novo” thyroid nodules in oncologic patients must be always considered and studied. PMID:25827295

  2. p53 and MDM2 in Renal Cell Carcinoma

    PubMed Central

    Noon, Aidan P.; Vlatković, Nikolina; Polański, Radosław; Maguire, Maria; Shawki, Howida; Parsons, Keith; Boyd, Mark T.

    2010-01-01

    Renal cell carcinoma (RCC) is the most common type of kidney cancer and follows an unpredictable disease course. To improve prognostication, a better understanding of critical genes associated with disease progression is required. The objective of this review was to focus attention on 2 such genes, p53 and murine double minute 2 (MDM2), and to provide a comprehensive summary and critical analysis of the literature regarding these genes in RCC. Information was compiled by searching the PubMed database for articles that were published or e-published up to April 1, 2009. Search terms included renal cancer, renal cell carcinoma, p53, and MDM2. Full articles and any supplementary data were examined; and, when appropriate, references were checked for additional material. All studies that described assessment of p53 and/or MDM2 in renal cancer were included. The authors concluded that increased p53 expression, but not p53 mutation, is associated with reduced overall survival/more rapid disease progression in RCC. There also was evidence that MDM2 up-regulation is associated with decreased disease-specific survival. Two features of RCC stood out as unusual and will require further investigation. First, increased p53 expression is tightly linked with increased MDM2 expression; and, second, patients who have tumors that display increased p53 and MDM2 expression may have the poorest overall survival. Because there was no evidence to support the conclusion that p53 mutation is associated with poorer survival, it seemed clear that increased p53 expression in RCC occurs independent of mutation. Further investigation of the mechanisms leading to increased p53/MDM2 expression in RCC may lead to improved prognostication and to the identification of novel therapeutic interventions. PMID:20052733

  3. Papillary renal cell carcinoma within a renal oncocytoma: case report of an incidental finding of a tumour within a tumour

    PubMed Central

    Rowsell, Corwyn; Fleshner, Neil; Marrano, Paula; Squire, Jeremy; Evans, Andrew

    2007-01-01

    The most common renal tumours are clear cell, papillary, chromophobe and collecting duct renal cell carcinomas (RCCs), and benign oncocytomas and angiomyolipomas. Tumours with hybrid features between some of these entities have been recognised; in particular, tumours with features of both chromophobe RCC and oncocytoma. Case reports describing one distinct type of primary renal tumour actually within another are very rare. The incidental finding of a papillary RCC located in an oncocytoma in a nephrectomy specimen from a 75‐year‐old man is described. Morphological criteria for each tumour type were completely satisfied and fluorescence in situ hybridisation detected the expected number of copies of chromosome 7 in the cells of each tumour type. The cells in the papillary tumour contained three copies, whereas the oncocytoma cells contained only two per nucleus. To our knowledge, this is the first report of a papillary RCC being identified within an oncocytoma. PMID:17405978

  4. Expression of Epstein-Barr virus in renal cell carcinoma.

    PubMed

    Shimakage, Misuzu; Kawahara, Kunimitsu; Harada, Shizuko; Sasagawa, Toshiyuki; Shinka, Toshiaki; Oka, Toshitsugu

    2007-07-01

    There have been few studies regarding the etiology of renal cell carcinoma. To examine the possible involvement of Epstein-Barr virus (EBV) in this disease, 9 renal cell carcinoma (RCC), 2 nephroblastoma (Wilms' tumor) and 2 RCC cell lines were subjected to mRNA in situ hybridization and indirect immunofluorescence staining. Messenger RNA in situ hybridization using BamHIW, EBNA LP, EBNA 2 and EBER1 probes of EBV revealed signals in all the examined samples, although some samples showed weak signals using the EBNA LP probe. Indirect immunofluorescence staining using anti-EBNA LP, anti-EBNA2, anti-LMP1 and anti-BZLF1 antibodies showed definitive fluorescence. PCR also revealed EBV DNA in all 8 RCC specimens including 7 cases other than hybridization and fluorescence. EBV infected all the RCC and nephroblastoma irrespective of the histological or clinical stage. On the other hand, EBV expression was stronger in papillary and clear cell-type RCC than chromophobe cell-type, as well as being stronger in the higher grades of RCC. These results suggest that the expression of EBV may be involved in the pathogenesis of RCC and nephroblastoma.

  5. In vitro effects of nanoparticles on renal cells

    PubMed Central

    L'Azou, Béatrice; Jorly, Joana; On, Dinhill; Sellier, Elisabeth; Moisan, Frédéric; Fleury-Feith, Jocelyne; Cambar, Jean; Brochard, Patrick; Ohayon-Courtès, Céline

    2008-01-01

    Background The ability of nanoparticles to cross the lung-blood barrier suggests that they may translocate to blood and to targets distant from their portal of entry. Nevertheless, nanotoxicity in organs has received little attention. The purpose of this study was to evaluate nanotoxicity in renal cells using in vitro models. Various carbon black (CB) (FW2–13 nm, Printex60-21 nm and LB101-95 nm) and titanium dioxide (TiO2-15 and TiO2-50 nm) nanoparticles were characterized on size by electron microscopy. We evaluated theirs effects on glomerular mesangial (IP15) and epithelial proximal tubular (LLC-PK1) renal cells, using light microscopy, WST-1 assay, immunofluorescence labeling and DCFH-DA for reactive oxygen species (ROS) assay. Results Nanoparticles induced a variety of cell responses. On both IP15 and LLC-PK1 cells, the smallest FW2 NP was found to be the most cytotoxic with classic dose-behavior. For the other NPs tested, different cytotoxic profiles were found, with LLC-PK1 cells being more sensitive than IP15 cells. Exposure to FW2 NPs, evidenced in our experiments as the most cytotoxic particle type, significantly enhanced production of ROS in both IP15 and LLC-PK1 cells. Immunofluorescence microscopy using latex beads indicated that depending on their size, the cells internalized particles, which accumulated in the cell cytoplasm. Additionally using transmission electronic microscope micrographs show nanoparticles inside the cells and trapped in vesicles. Conclusion The present data constitute the first step towards determining in vitro dose effect of manufactured CB and TiO2 NPs in renal cells. Cytotoxicological assays using epithelial tubular and glomerular mesangial cell lines rapidly provide information and demonstrated that NP materials exhibit varying degrees of cytotoxicity. It seems clear that in vitro cellular systems will need to be further developed, standardized and validated (relative to in vivo effects) in order to provide useful screening

  6. Predictive Performance of Physiologically Based Pharmacokinetic and Population Pharmacokinetic Modeling of Renally Cleared Drugs in Children

    PubMed Central

    Zhou, W; Johnson, TN; Xu, H; Cheung, SYA; Bui, KH; Li, J; Al‐Huniti, N

    2016-01-01

    Predictive performance of physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models of drugs predominantly eliminated through kidney in the pediatric population was evaluated. After optimization using adult clinical data, the verified PBPK models can predict 33 of 34 drug clearance within twofold of the observed values in children 1 month and older. More specifically, 10 of 11 of predicted clearance values were within 1.5‐fold of those observed in children between 1 month and 2 years old. The PopPK approach also predicted 19 of 21 drug clearance within twofold of the observed values in children. In summary, our analysis demonstrated both PBPK and PopPK adult models, after verification with additional adult pharmacokinetic (PK) studies and incorporation of known ontogeny of renal filtration, could be applied for dosing regimen recommendation in children 1 month and older for renally eliminated drugs in a first‐in‐pediatric study. PMID:27566992

  7. Stem Cell Conditioned Culture Media Attenuated Albumin-Induced Epithelial– Mesenchymal Transition in Renal Tubular Cells

    PubMed Central

    Hu, Junping; Zhu, Qing; Li, Pin-Lan; Wang, Weili; Yi, Fan; Li, Ningjun

    2015-01-01

    Background Proteinuria-induced epithelial-mesenchymal transition (EMT) plays an important role in progressive renal tubulointerstitial fibrosis in chronic renal disease. Stem cell therapy has been used for different diseases. Stem cell conditioned culture media (SCM) exhibits similar beneficial effects as stem cell therapy. The present study tested the hypothesis that SCM inhibits albumin-induced EMT in cultured renal tubular cells. Methods Rat renal tubular cells were treated with/without albumin (20 μmg/ml) plus SCM or control cell media (CCM). EMT markers and inflammatory factors were measured by Western blot and fluorescent images. Results Albumin induced EMT as shown by significant decreases in levels of epithelial marker E-cadherin, increases in mesenchymal markers fibroblast-specific protein 1 and α-smooth muscle actin, and elevations in collagen I. SCM inhibited all these changes. Meanwhile, albumin induced NF-κB translocation from cytosol into nucleus and that SCM blocked the nuclear translocation of NF-κB. Albumin also increased the levels of pro-inflammatory factor monocyte chemoattractant protein-1 (MCP)-1 by nearly 30 fold compared with control. SCM almost abolished albumin-induced increase of MCP-1. Conclusion These results suggest that SCM attenuated albumin-induced EMT in renal tubular cells via inhibiting activation of inflammatory factors, which may serve as a new therapeutic approach for chronic kidney diseases. PMID:25832005

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

    PubMed

    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.

  9. Occupational exposure to dusts and risk of renal cell carcinoma

    PubMed Central

    Karami, S; Boffetta, P; Stewart, P S; Brennan, P; Zaridze, D; Matveev, V; Janout, V; Kollarova, H; Bencko, V; Navratilova, M; Szeszenia-Dabrowska, N; Mates, D; Gromiec, J; Slamova, A; Chow, W-H; Rothman, N; Moore, L E

    2011-01-01

    Background: Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case–control study. Methods: General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression. Results: Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1–3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2–5.1), and brick dust (OR: 1.5; 95% CI: 1.0–2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed. Conclusion: Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings. PMID:21540858

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

    PubMed

    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.

  11. Blood Pressure, Proteinuria, and Renal Function Decline: Associations in a Large Community-Based Population.

    PubMed

    Hirayama, Atsushi; Konta, Tsuneo; Kamei, Keita; Suzuki, Kazuko; Ichikawa, Kazunobu; Fujimoto, Shouichi; Iseki, Kunitoshi; Moriyama, Toshiki; Yamagata, Kunihiro; Tsuruya, Kazuhiko; Kimura, Kenjiro; Narita, Ichiei; Kondo, Masahide; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi

    2015-09-01

    Hypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population. We analyzed data from a nationwide database of 141,514 subjects who participated in the annual "Specific Health Check and Guidance in Japan" checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation. After adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria. This study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. p-Cresol mediates autophagic cell death in renal proximal tubular cells.

    PubMed

    Lin, Hsin-Hung; Huang, Chiu-Ching; Lin, Tze-Yi; Lin, Ching-Yuang

    2015-04-02

    Higher serum level of p-cresol (PC) in chronic kidney disease (CKD) patients has been linked with CKD progression. The toxic effect of PC on diverse cells has been reported by prior studies, except for renal tubular cells. Both autophagy and apoptosis contribute to renal tubular cell death, yet evidence of its response to PC is limited and their crosstalk is still unclear. Autophagy is an important cellular process involved in toxin-induced cell death. Renal tubular cell death in tubular injury is thought to be one of the key events causing the progression of CKD. Thus, we treated rat (NRK-52E) and human (HRPTEC) renal proximal tubular cells (RPTC) with PC and found the cell proliferation was significantly decreased. Cell apoptosis was significantly increased and accompanied with the activation of autophagy as evidenced by increases in LC3-II, beclin 1 and Atg 4. We also found an increase of p62 by c-Jun activation. p62 accumulation could mediate the activation of caspase 8-dependent cell apoptosis. Conversely, knockdown of p62 by siRNA of p62 had the opposite effect by arresting LC3-II accumulation and promoting increasing cell viability. We conclude that PC triggered autophagic RPTC death via JNK-mediated p62 accumulation and then activated caspase 8-dependent cell death pathway. PC can be considered as one of the key events causing progression of CKD, which might affect drug disposition in CKD cases.

  13. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-10-18

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  14. Optimal management of renal cell carcinoma in the elderly: a review

    PubMed Central

    Quivy, Amandine; Daste, Amaury; Harbaoui, Asma; Duc, Sophie; Bernhard, Jean-Christophe; Gross-Goupil, Marine; Ravaud, Alain

    2013-01-01

    Both the aging population and the incidence of renal cell carcinoma (RCC) are growing, making the question of tumor management in the elderly a real challenge. Doctors should be aware of the importance of assessing this specific subpopulation. An aggressive therapeutic approach may be balanced by the benefit of the treatment — care or cure — and the life expectancy and willingness of the patient. The treatment for local disease can be surgery (radical or partial nephrectomy) or ablative therapies (radiofrequency, cryotherapy). Even if in most cases surgery is safe, complications such as alteration of renal function may occur, especially in the elderly, with physiological renal impairment at baseline. More recently, another option has been developed as an alternative: active surveillance. In the past decade, new drugs have been approved in the metastatic setting. All the phase 3 trials have included patients without a limit on age. Nevertheless, data concerning the elderly are still poor and concern only a very selective subpopulation. The toxicity profile of targeted agents may interfere with pre-existent comorbidities. Furthermore, the metabolism of several agents via cytochrome P450 can cause drug interaction. The importance of quality of life is a major factor with regard to management of therapy. Finally, to date, there is no recommendation of systematic a priori dose reduction in the elderly. In this review we describe the various possibilities of treatment for localized RCC or metastatic RCC in an aging population. PMID:23626463

  15. Overexpression of Numb suppresses growth, migration, and invasion of human clear cell renal cell carcinoma cells.

    PubMed

    Sima, Jin; Zhang, Bao; Yu, Yuanzi; Sima, Xinyuan; Mao, Yanxin

    2015-04-01

    The objective of the study was to investigate the impact of Numb on cell growth, cell migration, and invasion in human clear cell renal cell carcinoma (ccRCC). Endogenous expression of Numb was evaluated in the ccRCC cell lines (786-O, Caki-1, and Caki-2) and control reference human renal proximal tubular epithelial cells. Numb expression was decreased in the ccRCC cells compared with the control cells (P < 0.01). Then, 786-O and Caki-1 cells described as suitable transfection hosts were used in transfection to carry out biological function studies. The three experimental groups were as follows: Numb-ORF (transfected with Numb-ORF plasmid), blank-vector (transfected with pCMV6-entry), and cell-alone group (no DNA). Numb expression in the Numb-ORF groups was significantly higher than that in the controls (P < 0.01). Cell growth was remarkably reduced (P < 0.01), and the number of migrating or invading cells was reduced (P < 0.01) in the Numb-ORF groups compared with controls. Furthermore, the ratio of G0/G1 phase in the Numb-ORF group of 786-O cells was increased, and the S phase fraction and proliferation index was decreased (P < 0.01). Cyclin D1 and MMP-9 expression was reduced in the Numb-ORF groups compared with controls. Here, we have provided data for attenuated Numb expression in the ccRCC cells. Overexpression of Numb could induce G0/G1 phase arrest and inhibit cell proliferation, migration, and invasion. The suppressive effects might be due to downregulation of cyclin D1 or MMP-9 expression. Taken together, our data suggest that Numb may possibly function as a tumor suppressor involved in the carcinogenesis of ccRCC.

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

    PubMed

    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.

  17. A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 as Xp11 translocation renal cell carcinoma.

    PubMed

    Kurisaki-Arakawa, Aiko; Saito, Tsuyoshi; Takahashi, Michiko; Mitani, Keiko; Fukumura, Yuki; Nagashima, Yoji; Argani, Pedrum; Yao, Takashi

    2013-01-01

    Renal carcinomas associated with Xp11.2 translocations/transcription factor 3 (TFE3) gene fusion (Xp11 translocation RCC) are a rare subtype of renal cell carcinoma. A middle-aged Japanese man, who had a medical history of dialysis for more than 12 years, had bilateral renal cancers with a background of acquired cystic disease of the kidney and remarkable deposition of calcium oxalate in the tumorous area. The right renal tumor showed papillary architecture of clear cells with diffuse and strong immunoreactivity for TFE3 and focal and weak positivity for cathepsin K, suggesting a possibility of Xp11 translocation RCC. However, RT-PCR failed to detect any type of the reported fusion genes involving TFE3. Thus, the sample was sent for a TFE3 break-apart FISH assay in a renal tumor consultation service, which reported no evidence of TFE3 gene rearrangement. The right renal tumor was finally diagnosed as papillary renal cell carcinoma with cystic change. We report here a case of bilateral renal cell carcinoma in a patient undergoing long-term dialysis, which showed false-positive immunoreactivity for TFE3 immunostaining. Titration of TFE3 immunohistochemical staining (IHC) should be performed and cross-referenced with the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results.

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

    PubMed

    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.

  19. Delineating the Role of Various Factors in Renal Disposition of Digoxin through Application of Physiologically Based Kidney Model to Renal Impairment Populations

    PubMed Central

    Scotcher, Daniel; Jones, Christopher R.; Galetin, Aleksandra

    2017-01-01

    Development of submodels of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, advantage of such models in predicting clinical observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology. In the current study, a PBPK kidney model was developed for digoxin, accounting for the roles of organic anion transporting peptide 4C1 (OATP4C1) and P-glycoprotein (P-gp) in its tubular secretion, with the aim to investigate the impact of age and renal impairment (moderate to severe) on renal drug disposition. Initial PBPK simulations based on changes in glomerular filtration rate (GFR) underestimated the observed reduction in digoxin renal excretion clearance (CLR) in subjects with moderately impaired renal function relative to healthy. Reduction in either proximal tubule cell number or the OATP4C1 abundance in the mechanistic kidney model successfully predicted 59% decrease in digoxin CLR, in particular when these changes were proportional to reduction in GFR. In contrast, predicted proximal tubule concentration of digoxin was only sensitive to changes in the transporter expression/ million proximal tubule cells. Based on the mechanistic modeling, reduced proximal tubule cellularity and OATP4C1 abundance, and inhibition of OATP4C1-mediated transport, are proposed as possible causes of reduced digoxin renal secretion in renally impaired patients. PMID:28057840

  20. Delineating the Role of Various Factors in Renal Disposition of Digoxin through Application of Physiologically Based Kidney Model to Renal Impairment Populations.

    PubMed

    Scotcher, Daniel; Jones, Christopher R; Galetin, Aleksandra; Rostami-Hodjegan, Amin

    2017-03-01

    Development of submodels of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, advantage of such models in predicting clinical observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology. In the current study, a PBPK kidney model was developed for digoxin, accounting for the roles of organic anion transporting peptide 4C1 (OATP4C1) and P-glycoprotein (P-gp) in its tubular secretion, with the aim to investigate the impact of age and renal impairment (moderate to severe) on renal drug disposition. Initial PBPK simulations based on changes in glomerular filtration rate (GFR) underestimated the observed reduction in digoxin renal excretion clearance (CLR) in subjects with moderately impaired renal function relative to healthy. Reduction in either proximal tubule cell number or the OATP4C1 abundance in the mechanistic kidney model successfully predicted 59% decrease in digoxin CLR, in particular when these changes were proportional to reduction in GFR. In contrast, predicted proximal tubule concentration of digoxin was only sensitive to changes in the transporter expression/ million proximal tubule cells. Based on the mechanistic modeling, reduced proximal tubule cellularity and OATP4C1 abundance, and inhibition of OATP4C1-mediated transport, are proposed as possible causes of reduced digoxin renal secretion in renally impaired patients. Copyright © 2017 by The Author(s).

  1. Diagnosis and Management of Hereditary Renal Cell Cancer.

    PubMed

    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.

  2. Management of metastatic renal cell carcinoma – mini review

    PubMed Central

    Pandey, Himanshu; Sood, Swapan

    2015-01-01

    The management of metastatic renal cell carcinoma (mRCC) has evolved considerably in the last decade. A number of different systemic molecular targeted agents that have been recently approved have improved the survival of patients with mRCC. This mini-review focuses on the implementation of multi-modality therapy in the management of mRCC and the approved indications of the various available novel agents. These novel agents have expanded our armamentarium and improved clinical outcomes of this challenging disease that has considerable biological heterogeneity and clinical variability. PMID:28326262

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

    PubMed

    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.

  4. CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma.

    PubMed

    Sukov, William R; Ketterling, Rhett P; Lager, Donna J; Carlson, Austin W; Sinnwell, Jason P; Chow, George K; Jenkins, Robert B; Cheville, John C

    2009-09-01

    Renal oncocytoma is a benign tumor occurring singly or as multiple synchronous lesions. The histologic features of renal oncocytoma may overlap with those of chromophobe renal cell carcinoma. Chromosomal translocations involving the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36 chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1 overexpression by immunohistochemistry, and alterations of the CCND1 gene by fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were negative for cyclin D1 overexpression and alterations of CCND1. Of the 63 renal oncocytomas, 21 (33%) showed cyclin D1 overexpression. Of 21 renal oncocytomas with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57%). A CCND1 rearrangement was also identified in 1 (2%) of the 42 renal oncocytomas without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1 overexpression, 16 (38%) were from patients with multiple renal oncocytomas at nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5%) patient had multiple renal oncocytomas (P = .006). Of the 25 patients whose original tumor showed no cyclin D1 overexpression, 8 (32%) developed a subsequent renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1 overexpression had a subsequent renal oncocytoma (P = .016). The findings of this study suggest that renal oncocytomas lacking cyclin D1 overexpression may be associated with the development of multiple renal oncocytomas and that these patients are more likely to develop subsequent renal oncocytomas suggesting the need for more frequent clinical for these patients and little need for follow-up in patients with renal oncocytomas overexpressing cyclin D1. The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in

  5. Cell Adhesion Molecules in Chemically-Induced Renal Injury

    PubMed Central

    Prozialeck, Walter C.; Edwards, Joshua R.

    2007-01-01

    Cell adhesion molecules are integral cell-membrane proteins that maintain cell-cell and cell-substrate adhesion, and in some cases, act as regulators of intracellular signaling cascades. In the kidney, cell adhesion molecules such as the cadherins, the catenins, ZO-1, occludin and the claudins are essential for maintaining the epithelial polarity and barrier integrity that are necessary for the normal absorption/excretion of fluid and solutes. A growing volume of evidence indicates that these cell adhesion molecules are important early targets for a variety of nephrotoxic substances including metals, drugs, and venom components. In addition, it is now widely appreciated that molecules such as ICAM-1, the integrins and selectins play important roles in the recruitment of leukocytes and inflammatory responses that are associated with nephrotoxic injury. This review summarizes the results of recent in vitro and in vivo studies indicating that these cell adhesion molecules may be primary molecular targets in many types of chemically-induced renal injury. Some of the specific agents that are discussed include Cd, Hg, Bi, cisplatin, aminoglycoside antibiotics, S-(1,2-dichlorovinyl-L-cysteine) (DCVC) and various venom toxins. This review also includes a discussion of the various mechanisms by which these substances can affect cell adhesion molecules in the kidney. PMID:17316817

  6. The loss of renal dendritic cells and activation of host adaptive immunity are long-term effects of ischemia/reperfusion injury following syngeneic kidney transplantation.

    PubMed

    Ozaki, Kikumi S; Kimura, Shoko; Nalesnik, Michael A; Sico, Rita M; Zhang, Matthew; Ueki, Shinya; Ross, Mark A; Stolz, Donna B; Murase, Noriko

    2012-05-01

    Ischemia/reperfusion injury associated with kidney transplantation induces profound acute injury, influences early graft function, and affects long-term graft outcomes. To determine whether renal dendritic cells play any role during initial innate ischemia/reperfusion injury and the subsequent development of adaptive immune responses, we studied the behavior and function of renal graft and host infiltrating dendritic cells during early and late phases of renal ischemia/reperfusion injury. Wild type to green fluorescent protein (GFP) transgenic rat kidney transplantation was performed with and without 24-h cold storage. Ischemia/reperfusion injury in cold-stored grafts resulted in histopathological changes of interstitial fibrosis and tubular atrophy by 10 weeks, accompanied by upregulation of mRNAs of mediators of interstitial fibrosis and inflammation. In normal rat kidneys, we identified two populations of renal dendritic cells, predominant CD103(-)CD11b/c(+) and minor CD103(+)CD11b/c(+) cells. After transplantation without cold storage, grafts maintained CD103(-) but not CD103(+) GFP-negative renal dendritic cells for 10 weeks. In contrast, both cell subsets disappeared from cold-stored grafts, which associated with a significant GFP-expressing host CD11b/c(+) cell infiltration that included CD103(+) dendritic cells with a TNF-α-producing phenotype. These changes in graft/host dendritic cell populations were associated with progressive infiltration of host CD4(+) T cells with effector/effector-memory phenotypes and IFN-γ secretion. Thus, renal graft ischemia/reperfusion injury caused graft dendritic cell loss and was associated with progressive host dendritic cell and T-cell recruitment. Renal-resident dendritic cells might function as a protective regulatory network.

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

    PubMed Central

    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

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

    PubMed

    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.

  9. Multiple metastatic renal cell carcinoma isolated to pancreas.

    PubMed

    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.

  10. The Role of Everolimus in Renal Cell Carcinoma

    PubMed Central

    Valdivieso, Roger; Dell’Oglio, Paolo; Trudeau, Vincent; Larcher, Alessandro; Karakiewicz, Pierre I.

    2015-01-01

    Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

  11. Renal cell carcinoma: Atypical metastasis to inguinal lymph nodes

    PubMed Central

    Chaudhry, Qamar Saeed; Bhatty, Tanweer Ahmed Naveed; Khan, Ziauddin; Osman, Elsawi Medani

    2017-01-01

    Renal cell carcinoma (RCC) is a common tumor of the urinary tract. It is known to have variable presentations due to the extremely vascular nature of the organ. RCC are known to metastasize to lungs, bone, and brain commonly but atypical metastasis to various sites are reported in literature but as very rare pathology. We report a case of a 60-year-old female who presented with multiple inguinal and axillary lymph node enlargements which on excision biopsy showed metastatic RCC. RCC can present with synchronous metastatic deposits in the various organs. RCC can metastasize to some atypical sites as well such as thyroid, orbit, and neck as mentioned earlier in literature. The patient presenting with extra-regional lymph nodes like inguinal and axillary is extremely rare, and so far only one clinical case could be found from India in 2008. A 61-year-old female presented in the emergency department with left flank pain and hematuria. Imaging showed left swollen kidney but multiple lymph nodes in retroperitoneum, left inguinal and axillary region. Excisional biopsy confirmed metastatic renal clear cell carcinoma. The case was referred to an oncologist after left radical nephrectomy for further treatment. Renal cancer is quite common aggressive disease. Due to its vascular nature, it may present quite atypically as evident from literature. Although treatment of metastatic carcinoma is still controversial surgery is the mainstay of treatment and guidelines consider metastasectomy and cytoreductive nephrectomy as valid option followed by targeted systemic therapies. RCC has quite a high potential to metastasize in the versatile pattern, in our case, it is evident that valid management is still surgery but needs support from the multidisciplinary team. PMID:28216937

  12. Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4.

    PubMed

    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; Anders, Hans-Joachim

    2012-08-01

    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.

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

    PubMed Central

    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

  14. Renal cell carcinoma metastatic to gallbladder: a survival advantage to simultaneous nephrectomy and cholecystectomy.

    PubMed

    Hellenthal, Nicholas J; Stewart, Gregory S; Cambio, Angelo J; Delair, Sean M

    2007-01-01

    Renal cell carcinoma is a relatively uncommon cancer. Patients presenting with a renal adenocarcinoma are often found to have evidence of metastatic disease at the time of diagnosis. Herein, we describe the case of a 39-year-old male with renal cell carcinoma and a synchronous metastatic focus to the gallbladder. The patient underwent a successful simultaneous nephrectomy and cholecystectomy and is doing well 30 months after surgery without evidence of disease recurrence. A thorough metastatic work-up along with aggressive surgical intervention in patients with renal cell carcinoma and unusual metastatic foci can provide a long-term favorable outcome.

  15. Renal fossa recurrence after nephrectomy for renal cell carcinoma: prognostic features and oncological outcomes.

    PubMed

    Psutka, Sarah P; Heidenreich, Mark; Boorjian, Stephen A; Bailey, George C; Cheville, John C; Stewart-Merrill, Suzanne B; Lohse, Christine M; Atwell, Thomas D; Costello, Brian A; Leibovich, Bradley C; Thompson, R Houston

    2017-01-01

    To describe the clinicopathological features associated with increased risk of renal fossa recurrence (RFR) after radical nephrectomy (RN) and to describe the prognostic features associated with cancer-specific survival (CSS) among patients with RFR treated with primary locally directed therapy, systemically directed therapy or expectant management. The records of 2 502 patients treated with RN for unilateral, sporadic, localized renal cell carcinoma (RCC) between 1970 and 2006 were reviewed. CSS after RFR was estimated using the Kaplan-Meier method. Associations with the development of RFR and CSS after RFR were evaluated using Cox proportional hazards regression models. A total of 33 (1.3%) patients developed isolated RFR (iRFR) and 30 (1.2%) patients developed RFR in the setting of synchronous metastases after RN (study cohort, N = 63). The median follow-up for the series was 9.0 years after RN and 6.0 years after RFR diagnosis. On multivariable analysis, advanced pathological stage (pT2: hazard ratio [HR] 4.36, P = 0.004; pT3/4: HR 4.39, P = 0.003) and coagulative necrosis (HR 2.71, P = 0.006) were independently associated with increased risk of iRFR. The median time to recurrence was 1.5 years after RN among the 33 patients with iRFR, and 1.4 years among all patients. Overall, the median CSS was 2.5 years after diagnosis of iRFR, 1.3 years after RFR in the setting of synchronous metastases, and 2.2 years overall. After primary locally directed therapy (surgery, ablation or radiation), systemic therapy or expectant management, the 3-year CSS rates among patients with iRFR were 63%, 50% and 13% (P = 0.001) and were 64%, 50% and 28% (P = 0.006) among all patients, respectively. On multivariable analysis, when compared with observation, locally directed therapies were associated with a significantly decreased risk of death from RCC (HR 0.26, P < 0.001). Renal fossa recurrence is a rare event after RN for RCC and portends a poor prognosis, even in the absence of

  16. PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma?

    PubMed Central

    Barr, Meaghan L; Jilaveanu, Lucia B; Camp, Robert L; Adeniran, Adebowale J; Kluger, Harriet M; Shuch, Brian

    2015-01-01

    Aims Immunohistochemical stains have greatly improved the diagnostic accuracy of renal cell carcinoma (RCC) for primary and distant tumours. We evaluate a marker that has recently been incorporated in clinical practice, PAX-8, in primary and metastatic RCCs. Methods Two distinct tissue microarrays were used, one consisting of over 334 renal tumours, 294 with adjacent normal kidney and the other with 40 matched nephrectomy and metastatic sites of RCC. PAX-8 expression was assessed by a method of quantitative immunofluorescence. Results PAX-8 was positive in 96% (146/152) of normal renal tissue and 83% (227/272) of renal tumours. PAX-8 staining was positive in clear cell, papillary and chromophobe tumours in 80% (165/207), 95% (39/41) and 100% (6/6) of samples, respectively. Overall, intensity of PAX-8 expression was significantly higher in RCC metastatic sites than in the primary site (p=0.0047), however, in matched sites there was no statistically significant difference in the proportion of positive versus negative specimens (p=0.274). Conclusions As the role of molecular markers expands in the diagnostic algorithm, this study confirms that PAX-8 expression is a useful diagnostic marker for RCC. PAX-8 expression was found in the primary tumour and distant sites. Compared with normal tissue and other histological types, clear cell RCC has lower PAX-8 expression and is less frequently positive, therefore, the lack of expression does not exclude a tumour of renal origin. PMID:25315900

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

    PubMed

    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.

  18. The utility of tetraspanin CD9 as a biomarker for metastatic clear cell renal cell carcinoma.

    PubMed

    Garner, Jo M; Herr, Michael J; Hodges, Kurt B; Jennings, Lisa K

    2016-02-26

    The use of tetraspanin CD9 as a biomarker for renal cell carcinomas (RCC) has been explored with minor conclusions. Identification of a biomarker that not only distinguishes between the different types of renal cell carcinomas, but also predicts the metastatic potential of these tumors would significantly advance diagnosis and prognosis of kidney cancers. We utilized established cell lines to better understand the contribution of CD9 to the metastatic potential of clear cell renal cell carcinomas, and then applied our findings to the TCGA database and immunohistochemical analysis of human samples based on tumor grading to determine the utility of CD9 as a biomarker for RCC. Clear cell renal cell carcinoma (ccRCC) cell expression of tetraspanin CD9 was compared to normal kidney cells and found to be elevated. Upon knockdown of CD9, ccRCC cells obtained a more metastatic phenotype. We found E-cadherin expression to be repressed and the endothelial to mesenchymal transition markers Snail, Twist1, and Zeb1 to be elevated upon CD9 knockdown. Upon observing these gene expression changes in the TCGA database and in 10 cases, we found that CD9 and E-cadherin expression was lowered in higher grade ccRCC tumors. There was a significant correlation between CD9 and either E-cadherin, Snail, or Zeb1 in these tumors. Collectively, using tetraspanin CD9 in tandem with E-cadherin as a biomarker in renal cell carcinoma will help to not only distinguish between types, but also predict the metastatic potential of RCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Splenectomy and risk of renal and perinephric abscesses: A population-based cohort study in Taiwan.

    PubMed

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2016-08-01

    Little epidemiological research is available on the relationship between splenectomy and renal and perinephric abscesses. The purpose of the study was to examine this issue in Taiwan.We conducted a population-based retrospective cohort study using the hospitalization dataset of the Taiwan National Health Insurance Program. A total of 16,426 participants aged 20 and older who were newly diagnosed with splenectomy from 1998 to 2010 were assigned to the splenectomy group, whereas 65,653 sex-matched, age-matched, and comorbidity-matched, randomly selected participants without splenectomy were assigned to the nonsplenectomy group. The incidence of renal and perinephric abscesses at the end of 2011 was measured in both groups. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for risk of renal and perinephric abscesses associated with splenectomy and other comorbidities including cystic kidney disease, diabetes mellitus, urinary tract infection, and urolithiasis.The overall incidence rate of renal and perinephric abscesses was 2.14-fold greater in the splenectomy group than that in the nonsplenectomy group (2.24 per 10,000 person-years vs 1.05 per 10,000 person-years, 95% CI 2.02, 2.28). After controlling for sex, age, cystic kidney disease, diabetes mellitus, urinary tract infection, and urolithiasis, the multivariable regression analysis demonstrated that the adjusted HR of renal and perinephric abscesses was 2.24 for the splenectomy group (95 % CI 1.30, 3.88), when compared with the nonsplenectomy group. In further analysis, the adjusted HR markedly increased to 7.69 for those comorbid with splenectomy and diabetes mellitus (95% CI 3.31, 17.9).Splenectomy is associated with renal and perinephric abscesses, particularly comorbid with diabetes mellitus. In view of its potential morbidity and mortality, clinicians should consider the possibility of renal and perinephric abscesses when

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

    PubMed

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Renal cell cancer: state of the art in adjuvant therapy.

    PubMed

    Buti, Sebastiano; Rovere, Rodrigo K

    2010-11-01

    Renal cell cancer is fastly growing in incidence worldwide. No adjuvant therapy has been unarguably proven feasible so far, although an autologous vaccine has achieved a significant benefit. An effective agent in adjuvant therapy against renal cell cancer must achieve several goals. It should be relatively non toxic, have estabilished efficacy in the metastatic setting, and have demonstrated efficacy against the standard of care in randomized phase III trials. The development of adjuvant therapy requires the properly identification of patients at highest risk of relapse, as potential benefactors of adjuvant therapy development. Our ability to predict when and where patients will recur has much room for improvement. Therefore several models and nomograms including the most important prognostic and predictive factors have been developed. Nevertheless, during the past few years, major advances have been made concerning the metastatic setting of the disease with the arrival of new drug classes such as tyrosine kinase inhibitors and monoclonal antibodies, strongly improving overall and progression free survivals, renewing hopes on activity regarding the adjuvant therapy. Several trials are today in progress to evaluate the effectiveness of antiangiogenic agents in this area. An overall review of the completed and upcoming trials and patents shall be discussed here.

  2. IL-37 mediates the antitumor activity in renal cell carcinoma.

    PubMed

    Jiang, Yazhuo; Wang, Yili; Liang, Liang; Gao, Yang; Chen, Juan; Sun, Yi; Cheng, Yongyi; Xu, Yonggang

    2015-11-01

    Interleukin (IL)-37 is a natural suppressor of innate inflammatory and immune responses. IL-37 plays an important role in renal function and antitumor activity. The aim of this study was to investigate the role of IL-37 in renal cell carcinoma (Rcc). Serum IL-37 levels in 120 Rcc patients and 50 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). The Rcc cell lines A498 and Caki-1 were cultured with 0-100 ng/mL of recombinant human IL-37 protein (rhIL-37). Cancer cells were transfected with or without pcDNA3.1-IL-6 to alter IL-6 expression. Cell migration, proliferation, and apoptosis were tested by wound-healing assay, MTT, and flow cytometry, respectively. Levels of IL-6, pSTAT3 Y705, Bcl-2, cyclin D1, and HIF-1α were detected by qRT-PCR, ELISA, or western blot. Additionally, therapeutic effect of rhIL-37 was also confirmed in SCID mice. The expression of IL-37 was decreased in Rcc patients and was negatively correlated with tumor progression. In vitro, IL-37 markedly inhibited the migration and proliferation, and promoted apoptosis in Rcc cells. Furthermore, the expressions of IL-6, pSTAT3 Y705, HIF-1α, Bcl-2, and cyclin D1 were decreased by IL-37. However, these effects were reversed by the transfection of pcDNA3.1-IL-6. In vivo, tumor growth and gene expressions of IL-6 and HIF-1α were suppressed by IL-37. In conclusion, IL-37 might serve as a novel tumor suppressor in Rcc and exert its antitumor activity through inhibiting IL-6/STAT3 signaling.

  3. Autophagy protects renal tubular cells against cyclosporine toxicity.

    PubMed

    Pallet, Nicolas; Bouvier, Nicolas; Legendre, Christophe; Gilleron, Jerome; Codogno, Patrice; Beaune, Philippe; Thervet, Eric; Anglicheau, Dany

    2008-08-01

    A major side effect of the powerful immunosuppressive drug cyclosporine (CsA) is the development of a chronic nephrotoxicity whose mechanisms are not fully understood. Recent data suggest that tubular cells play a central role in the pathogenesis of chronic nephropathies. We have shown that CsA is responsible for endoplasmic reticulum (ER) stress in tubular cells. Autophagy has recently been described to be induced by ER stress and to alleviate its deleterious effects. In this study, we demonstrate that CsA induces autophagy in primary cultured human renal tubular cells through LC3II expression and autophagosomes visualization by electron microscopy. Autophagy is dependant on ER stress because various ER stress inducers activate autophagy, and salubrinal, an inhibitor of eIF2alpha dephosphorylation that protects cells against ER stress, inhibited LC3II expression. Furthermore, autophagy inhibition during CsA treatment with beclin1 siRNA significantly increases tubular cell death. Finally, immunohistochemical analysis of rat kidneys demonstrates a positive LC3 staining on injured tubular cells, suggesting that CsA induces autophagy in vivo. Taken together, these results demonstrate that CsA, through ER stress induction, activates autophagy as a protection against cell death.

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

    PubMed

    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.

  5. Incidence of Clear Cell Papillary Renal Cell Carcinoma in Low-Grade Renal Cell Carcinoma Cases: A 12-Year Retrospective Clinicopathologic Study From a Single Cancer Center.

    PubMed

    Gill, Simpal; Kauffman, Eric C; Kandel, Sirisa; George, Saby; Schwaab, Thomas; Xu, Bo

    2016-05-01

    Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity after 2004 World Health Organization classification of renal tumors. CCPRCC has unique histomorphological and immunohistochemical characteristics. The distinction of CCPRCC from renal cell carcinoma (RCC) with clear cell morphology is crucial because the former is considered to have a favorable clinical outcome. CCPRCC may be interpreted in the past as other renal cell carcinomas, particularly low-grade clear cell RCC. In this study, the frequency of CCPRCC in previously diagnosed low-grade RCC and its clinicopathologic features were examined. A total of 126 cases of stage T1a with low nuclear grade RCC were identified from 625 consecutive RCCs removed by radical/partial nephrectomy over 12-year period (2000-2011). Archival tissue sections were retrospectively reviewed along with patient medical charts. Eight cases (1.3% of all RCC, 6.3% of pT1a low grade RCC) with characteristic histologic features of CCPRCC were confirmed by immunohistochemical studies. Seven cases were previously diagnosed as clear cell RCC and one as multilocular cystic RCC. Radiographically, CCPRCC favored a mid-pole location in the kidneys. At a median follow-up period of 52 months (range 20-114.5 months), there were no cases of local or distant recurrence. In conclusion, CCPRCC is not uncommon among small low-grade RCC tumors. CCPRCC can be correctly recognized by its unique histomorphological features and confirmed by immunohistochemistry studies, which is important due to the excellent clinical outcome following resection. © The Author(s) 2015.

  6. Endothelial progenitor cells and asymmetric dimethylarginine after renal transplantation.

    PubMed

    Teplan, Vladimír; Mahrová, Andrea; Králová-Lesná, Ivana; Racek, Jaroslav; Valkovský, Ivo; Štollová, Milena

    2015-03-01

    Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 μmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 μmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx.

  7. PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

    ClinicalTrials.gov

    2017-04-04

    VHL Gene Mutation; VHL; VHL Syndrome; VHL Gene Inactivation; Von Hippel; Von Hippel-Lindau Disease; Von Hippel's Disease; Von Hippel-Lindau Syndrome, Modifiers of; Clear Cell Renal Cell Carcinoma; Clear Cell RCC; ccRCC

  8. Renal Cancer Stem Cells: Characterization and Targeted Therapies

    PubMed Central

    Sisti, Alessandro; Romagnani, Paola

    2016-01-01

    Renal cell carcinoma (RCC) is a major neoplasm with high incidence in western countries. Tumors are heterogeneous and are composed of differentiated cancer cells, stromal cells, and cancer stem cells (CSCs). CSCs possess two main properties: self-renewal and proliferation. Additionally, they can generate new tumors once transplanted into immunodeficient mice. Several approaches have been described to identify them, through the expression of cell markers, functional assays, or a combination of both. As CSCs are involved in the resistance mechanisms to radio- and chemotherapies, several new strategies have been proposed to directly target CSCs in RCC. One approach drives CSCs to differentiate into cancer cells sensitive to conventional treatments, while the other proposes to eradicate them selectively. A series of innovative therapies aiming at eliminating CSCs have been designed to treat other types of cancer and have not been experimented with on RCC yet, but they reveal themselves to be promising. In conclusion, CSCs are an important player in carcinogenesis and represent a valid target for therapy in RCC patients. PMID:27293448

  9. Foretinib (XL880): c-MET inhibitor with activity in papillary renal cell cancer.

    PubMed

    Logan, Theodore F

    2013-04-01

    Papillary renal cell cancer (RCC) constitutes approximately 10 % of renal cancers and is the commonest form after clear cell RCC, which accounts for approximately 75 % of cases. Until recently, most clinical trials in RCC were open to patients of all histologic types. Very recent clinical trials have been performed predominately in patients with clear cell RCC and relatively few trials have been done for patients with papillary RCC. The clinical characteristics of papillary RCC are less well appreciated because of both its relative rarity in the general oncology population and the lack of related clinical studies. This article reviews papillary RCC as a clinical entity separate from clear cell RCC. The MET signaling pathway, its association with increased invasion and progression of human cancer, and its dysregulation in papillary RCC is discussed. Lastly, foretinib, a multitargeted receptor tyrosine kinase inhibitor of several receptors, including MET and vascular endothelial growth factor receptor 2, is described in preclinical and phase I studies as well as in a phase II study in papillary RCC patients.

  10. Regulatory T cells participate in CD39-mediated protection from renal injury.

    PubMed

    Wang, Yuan Min; McRae, Jennifer L; Robson, Simon C; Cowan, Peter J; Zhang, Geoff Yu; Hu, Min; Polhill, Tania; Wang, Yiping; Zheng, Guoping; Wang, Ya; Lee, Vincent W S; Unwin, Robert J; Harris, David C H; Dwyer, Karen M; Alexander, Stephen I

    2012-09-01

    CD39 is an ecto-enzyme that degrades extracellular nucleotides, such as ATP, and is highly expressed on by the vasculature and circulating cells including Foxp3+ regulatory T (Treg) cells. To study the role of purinergic regulation in renal disease, we used the adriamycin nephropathy (AN) mouse model of chronic renal injury, using human CD39-transgenic (hCD39Tg) and wild-type (WT) BALB/c mice. Effects of CD39 expression by Treg cells were assessed in AN by adoptive transfer of CD4(+) CD25(+) and CD4(+) CD25(-) T cells isolated from hCD39Tg and WT mice. hCD39Tg mice were protected from renal injury in AN with decreased urinary protein and serum creatinine, and significantly less renal injury compared with WT mice. While WT CD25(+) and hCD39Tg CD25(-) T cells conferred some protection against AN, hCD39Tg CD25(+) Treg cells offered greater protection. In vitro studies showed direct pro-apoptotic effects of ATP on renal tubular cells. In conclusion, hCD39 expressed by circulating leukocytes and intrinsic renal cells limits innate AN injury. Specifically, CD39 expression by Treg cells contributes to its protective role in renal injury. These findings suggest that extracellular nucleotides mediate AN kidney injury and that CD39, expressed by Treg cells and other cells, is protective in this model.

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

    PubMed

    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.

  12. Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin.

    PubMed

    Wang, Yuan Min; Zhang, Geoff Yu; Wang, Yiping; Hu, Min; Wu, Huiling; Watson, Debbie; Hori, Shohei; Alexander, Ian E; Harris, David C H; Alexander, Stephen I

    2006-03-01

    Chronic proteinuric renal injury is a major cause of ESRD. Adriamycin nephropathy is a murine model of chronic proteinuric renal disease whereby chemical injury is followed by immune and structural changes that mimic human disease. Foxp3 is a gene that induces a regulatory T cell (Treg) phenotype. It was hypothesized that Foxp3-transduced Treg could protect against renal injury in Adriamycin nephropathy. CD4+ T cells were transduced with either a Foxp3-containing retrovirus or a control retrovirus. Foxp3-transduced T cells had a regulatory phenotype by functional and phenotypic assays. Adoptive transfer of Foxp3-transduced T cells protected against renal injury. Urinary protein excretion and serum creatinine were reduced (P<0.05), and there was significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates (P<0.01). It is concluded that Foxp3-transduced Treg cells may have a therapeutic role in protecting against immune injury and disease progression in chronic proteinuric renal disease.

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

    PubMed Central

    Wehler, Thomas C.; Graf, Claudine; Biesterfeld, Stefan; Brenner, Walburgis; Schadt, Jörg; Gockel, Ines; Berger, Martin R.; Thüroff, Joachim W.; Galle, Peter R.; Moehler, Markus; Schimanski, Carl C.

    2008-01-01

    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. PMID:19266088

  14. Targeted next-generation sequencing and non-coding RNA expression analysis of clear cell papillary renal cell carcinoma suggests distinct pathological mechanisms from other renal tumour subtypes.

    PubMed

    Lawrie, Charles H; Larrea, Erika; Larrinaga, Gorka; Goicoechea, Ibai; Arestin, María; Fernandez-Mercado, Marta; Hes, Ondrej; Cáceres, Francisco; Manterola, Lorea; López, José I

    2014-01-01

    Clear cell tubulopapillary renal cell carcinoma (CCPRCC) is a recently described rare renal malignancy that displays characteristic gross, microscopic and immunohistochemical differences from other renal tumour types. However, CCPRCC remains a very poorly understood entity. We therefore sought to elucidate some of the molecular mechanisms involved in this neoplasm by carrying out targeted next-generation sequencing (NGS) to identify associated mutations, and in addition examined the expression of non-coding (nc) RNAs. We identified multiple somatic mutations in CCPRCC cases, including a recurrent [3/14 cases (21%)] non-synonymous T992I mutation in the MET proto-oncogene, a gene associated with epithelial-to-mesenchymal transition (EMT). Using a microarray approach, we found that the expression of mature (n = 1105) and pre-miRNAs (n = 1105), as well as snoRNA and scaRNAs (n = 2214), in CCPRCC cases differed from that of clear cell renal cell carcinoma (CCRCC) or papillary renal cell carcinoma (PRCC) tumours. Surprisingly, and unlike other renal tumour subtypes, we found that all five members of the miR-200 family were over-expressed in CCPRCC cases. As these miRNAs are intimately involved with EMT, we stained CCPRCC cases for E-cadherin, vimentin and β-catenin and found that the tumour cells of all cases were positive for all three markers, a combination rarely reported in other renal tumours that could have diagnostic implications. Taken together with the mutational analysis, these data suggest that EMT in CCPRCC tumour cells is incomplete or blocked, consistent with the indolent clinical course typical of this malignancy. In summary, as well as describing a novel pathological mechanism in renal carcinomas, this study adds to the mounting evidence that CCPRCC should be formally considered a distinct entity. Microarray data have been deposited in the GEO database [GEO accession number (GSE51554)]. Copyright © 2013 Pathological Society of Great Britain and Ireland

  15. Displacement of the Spleen Mimicking Renal Cell Cancer Recurrence Post-Nephrectomy: A Case Report

    PubMed Central

    Emanuels, Carolina S.; Timmerman, Krista D.; Aijaz, Tabish; Nguyen, Thu-Cuc; Jest, Nathaniel; Drane, Walter E.; Gilbert, Scott M.; Crispen, Paul L.; Su, Li-Ming; Deitte, Lori A.

    2015-01-01

    Local regional recurrence of renal cell cancer post-nephrectomy most often occurs within three years after surgery. Post-nephrectomy, many processes may mimic RCC recurrence. We present the case of a 75 year-old Caucasian male patient with a mass in his renal fossa post-nephrectomy for renal cell cancer, suggesting local recurrence. Use of the technetium-99m sulfur colloid scan showed that the mass was his spleen which had been displaced into the renal fossa. With high index of suspicion, characterization of these processes as splenic in origin would prevent subjecting patients to risks of biopsy or even surgery.

  16. Metabolic profiling reveals key metabolic features of renal cell carcinoma.

    PubMed

    Catchpole, Gareth; Platzer, Alexander; Weikert, Cornelia; Kempkensteffen, Carsten; Johannsen, Manfred; Krause, Hans; Jung, Klaus; Miller, Kurt; Willmitzer, Lothar; Selbig, Joachim; Weikert, Steffen

    2011-01-01

    Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. α-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.

  17. Prospective study of percutaneous cryoablation combined with allogenic NK cell immunotherapy for advanced renal cell cancer.

    PubMed

    Lin, Mao; Xu, Kecheng; Liang, Shuzhen; Wang, Xiaohua; Liang, Yinqing; Zhang, Mingjie; Chen, Jibing; Niu, LiZhi

    2017-03-05

    In this study, the clinical efficacy of cryosurgery combined with allogenic NK cell immunotherapy for advanced renal cell cancer was evaluated. From July to December 2016, we enrolled 60 patients who met the enrollment criteria and divided them into two groups: (1) the simple cryoablation group (n=30); and (2) the cryoablation combined with allogenic NK cells group (n=30). The clinical efficacy, quality of life, immune function, and other related indicators were evaluated. Combining allogeneic NK cells with cryoablation had a synergistic effect, not only enhancing the immune function and improving the quality of life of the patients, but also significantly exhibiting good clinical efficacy of the patients. This study is the first clinical trial that has evaluated the safety and efficacy of allogenic NK cells combined with cryosurgery for the treatment of renal cell cancer.

  18. Relationships between protein intake and renal function in a Japanese general population: NIPPON DATA90.

    PubMed

    Higashiyama, Aya; Watanabe, Makoto; Kokubo, Yoshihiro; Ono, Yuu; Okayama, Akira; Okamura, Tomonori

    2010-01-01

    It has been considered that reducing protein intake is one of important measures to delay the progression of chronic kidney disease (CKD). However, the relationship between protein intake and renal function is still uncertain, especially in relatively healthy general population. 7404 individuals (3099 men and 4305 women) who participated in both National Survey on Circulatory Disorders and National Nutrition Survey in 1990 and were free from past history of renal diseases were included in the present study. We estimated sex-specific age- and multivariate-adjusted glomerular filtration rate (GFR) and odds ratios for the presence of CKD according to the quartiles of protein (total, animal, vegetable) intake per body weight (kg). There were significant differences in each protein intake among the age groups in both men and women. Both participants with and without CKD took more protein intake than that of each recommended level. There were positive relationships between GFR and the quartiles of each protein intake in both sexes. The odds ratios for the presence of CKD were significantly decreased in the higher quartile of protein intake in women. The higher protein intake was associated with higher GFR in both sexes and low prevalence of CKD in women. However, further studies are needed to conclude the relationships between protein intake and renal function.

  19. Renal effects evolution in a Chinese population after reduction of cadmium exposure in rice

    SciTech Connect

    Wu Xunwei; Liang Yihuai; Jin Taiyi Ye Tingting; Kong Qinghu; Wang Zaijuan; Lei Lijian; Bergdahl, Ingvar A.; Nordberg, Gunnar F.

    2008-10-15

    Cadmium is a well-known nephrotoxic agent with extremely long biological half-time of 10-30 years in human. To investigate the evolution of cadmium-induced renal effects in the population, a number of 148 residents who lived in cadmium-polluted area were followed-up for 3 years after the reduction of cadmium exposure in rice. Urinary cadmium (UCd), {beta}{sub 2}-microglobulin (B2M) and albumin (ALB) were analyzed in 1995 and 1998, respectively. The results demonstrated that the changes of renal effects of residents depended on the levels of UCd before inflow of cadmium to human body declined. In cases where UCd were less than 10 {mu}g/g creatinine in 1995, evidence was found indicating significant decreases in proteinuria (i.e., B2M and ALB) 3 years later, whereas, in cases where the excretion of UCd exceeded 10 {mu}g/g creatinine in 1995, progression was observed. The study of dose-response relationships between UCd and B2M or ALB also showed that the cadmium-induced renal dysfunction might be reversible if UCd concentration was low-level before exposure decreasing, otherwise it might be irreversible or aggravated.

  20. Self-reported sleep duration and daytime napping are associated with renal hyperfiltration in general population.

    PubMed

    Lin, Miao; Su, Qing; Wen, Junping; Wei, Shichao; Yao, Jin; Huang, Huibin; Liang, Jixing; Li, Liantao; Lin, Wei; Lin, Lixiang; Lu, Jieli; Bi, Yufang; Wang, Weiqing; Ning, Guang; Chen, Gang

    2017-02-26

    Renal hyperfiltration (RHF) has emerged as a novel marker of early renal damage in various conditions such as diabetes and metabolic syndrome. Aberrant sleep duration and excessive daytime napping may affect the development of chronic kidney disease (CKD). In this study, the association between sleep duration, daytime napping, and renal hyperfiltration was assessed. This study was conducted in three communities in China. A total of 16,119 community volunteers (5735 males and 10,384 females) aged 40-65 years without CKD were included for the study. Participants with short sleep duration (<6 h/day) or long sleep duration (≥10 h/day) were at a significantly increased risk of renal hyperfiltration. The fully adjusted ORs (95% CI) were 2.112 (1.107, 4.031) and 2.071 (1.504, 2.853), respectively (P < 0.05). In addition, those who took naps longer than 1.5 h per day had a higher risk of renal hyperfiltration compared with those without napping (OR 1.400, 95% CI 1.018-1.924). Further joint analysis indicated that participants with long sleep duration (≥10 h/day) had a more than twofold increased risk of RHF regardless of nap status compared with those who slept 8-9 h per day without daytime napping. The association between sleep duration or daytime napping and RHF could not be explained by the influence of sleep quality. Additional subgroup analysis showed long sleep duration (≥9 h/day) and long daytime napping (≥1.5 h) were associated with an increased risk of RHF among individuals with good sleep quality. Sleep duration less than 6 h/day or more than 10 h/day and long daytime napping tend to be associated with an increased risk of renal hyperfiltration in middle-aged general population, and this relationship was independent of diabetes, hypertension, obesity, or poor sleep quality.

  1. [Expression of LIM and SH3 protein 1 in renal clear cell carcinoma and its effects on invasion and migration of renal clear cell carcinoma 786-O cells].

    PubMed

    Jin, B; Gao, L; Li, W; Chen, J C; Wen, R M; Wang, J Q

    2017-03-23

    Objective: To investigate the expression of LIM and SH3 protein 1 (LASP1) in renal cell carcinoma and its significance in the invasion and migration of renal clear cell carcinoma 786-O cell line. Methods: The expression level of LASP1 in 41 cases of renal cell carcinoma tissues and normal renal tissues was analyzed by immunohistochemistry. The relationship between the expression level of LASP1 and clinical characteristics was further analyzed. Expression of LASP1 in 10 cases of tumor tissues with or without lymph node metastasis was analyzed by Western blot. Furthermore, small interfering RNA (siRNA) targeting LASP1 was constructed and transfected into 786-O cells to downregulate LASP1 expression. The interference effect of LASP1 siRNA on LASP1 protein and the expression of related proteins in epithelial mesenchymal transition (EMT) pathway were detected by Western blot. The effects of LASP1 knockdown on cell proliferation, migration and invasion and gene expression were then assessed using CCK8 assay, transwell cell migration system and western blot analysis, respectively. Results: The positive rate of LASP1 expression in renal clear cell carcinoma tissues was 90.2% (37/41), which was significantly higher than that in the adjacent tissues (29.3%, P=0.002). The expression of LASP1 in renal cell carcinoma was positively correlated with lymph node metastasis and TNM stage of renal cell carcinoma (P<0.05). The results of Western blot showed that LASP1 (0.696±0.053) was highly expressed in renal cell carcinoma (1.459±0.628), especially in cases with lymph node metastasis (2.692±0.186, P<0.05). The LASP1 siRNA remarkably down-regulated the expression of LASP1 protein in 786-O cells. The abilities of proliferation, invasion and migration of 786-O cells were decreased significantly in the LASP1 siRNA groups.The relative expression of E-cadherin protein in the siRNA group (0.848±0.020) was significantly higher than those in the siRNA-NC group (0.671±0.018) and control

  2. Crossing Paths in Human Renal Cell Carcinoma (hRCC)

    PubMed Central

    Gallego, Guadalupe Aparicio; Villaamil, Vanessa Medina; Grande, Enrique; Caínzos, Isabel Santamarina; Antón Aparicio, Luís M.

    2012-01-01

    Historically, cell-signaling pathways have been studied as the compilation of isolated elements into a unique cascade that transmits extracellular stimuli to the tumor cell nucleus. Today, growing evidence supports the fact that intracellular drivers of tumor progression do not flow in a single linear pathway, but disseminate into multiple intracellular pathways. An improved understanding of the complexity of cancer depends on the elucidation of the underlying regulatory networks at the cellular and intercellular levels and in their temporal dimension. The high complexity of the intracellular cascades causes the complete inhibition of the growth of one tumor cell to be very unlikely, except in cases in which the so-called “oncogene addiction” is known to be a clear trigger for tumor catastrophe, such as in the case of gastrointestinal stromal tumors or chronic myeloid leukemia. In other words, the separation and isolation of the driver from the passengers is required to improve accuracy in cancer treatment. This review will summarize the signaling pathway crossroads that govern renal cell carcinoma proliferation and the emerging understanding of how these pathways facilitate tumor escape. We outline the available evidence supporting the putative links between different signaling pathways and how they may influence tumor proliferation, differentiation, apoptosis, angiogenesis, metabolism and invasiveness. The conclusion is that tumor cells may generate their own crossroads/crosstalk among signaling pathways, thereby reducing their dependence on stimulation of their physiologic pathways. PMID:23202921

  3. Sunitinib activates Axl signaling in renal cell cancer.

    PubMed

    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.

  4. Radiosensitization by Inhibiting STAT1 in Renal Cell Carcinoma

    SciTech Connect

    Hui Zhouguang; Tretiakova, Maria; Zhang Zhongfa; Li Yan; Wang Xiaozhen; Zhu, Julie Xiaohong; Gao Yuanhong; Mai Weiyuan; Furge, Kyle; Qian Chaonan; Amato, Robert; Butler, E. Brian

    2009-01-01

    Purpose: Renal cell carcinoma (RCC) has been historically regarded as a radioresistant malignancy, but the molecular mechanism underlying its radioresistance is not understood. This study investigated the role of signal transducer and activator of transcription 1 (STAT1), a transcription factor downstream of the interferon-signaling pathway, in radioresistant RCC. Methods and Materials: The expressions of STAT1 and STAT3 in 164 human clear cell RCC samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were examined by microarray expression profiling and immunohistochemistry. Western blotting was performed to evaluate the total and phosphorylated STAT1 expression in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL-116 (human fibroblast), and CRL-1441 (G-401) (human Wilms tumor). STAT1 was reduced or inhibited by fludarabine and siRNA, respectively, and the effects on radiation-induced cell death were investigated using clonogenic assays. Results: STAT1 expression, but not STAT3 expression, was significantly greater in human RCC samples (p = 1.5 x 10{sup -8} for clear cell; and p = 3.6 x 10{sup -4} for papillary). Similarly, the expression of STAT1 was relatively greater in the two RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA, significantly increasing the radiosensitivity in both RCC cell lines. Conclusion: This is the first study reporting the overexpression of STAT1 in human clear cell and papillary RCC tissues. Radiosensitization in RCC cell lines was observed by a reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data suggest that STAT1 may play a key role in RCC radioresistance and manipulation of this pathway may enhance the efficacy of radiotherapy.

  5. Increased Perfusion Pressure Drives Renal T-Cell Infiltration in the Dahl Salt-Sensitive Rat.

    PubMed

    Evans, Louise C; Petrova, Galina; Kurth, Theresa; Yang, Chun; Bukowy, John D; Mattson, David L; Cowley, Allen W

    2017-09-01

    Renal T-cell infiltration is a key component of salt-sensitive hypertension in Dahl salt-sensitive (SS) rats. Here, we use an electronic servo-control technique to determine the contribution of renal perfusion pressure to T-cell infiltration in the SS rat kidney. An aortic balloon occluder placed around the aorta between the renal arteries was used to maintain perfusion pressure to the left kidney at control levels, ≈128 mm Hg, during 7 days of salt-induced hypertension, whereas the right kidney was exposed to increased renal perfusion pressure that averaged 157±4 mm Hg by day 7 of high-salt diet. The number of infiltrating T cells was compared between the 2 kidneys. Renal T-cell infiltration was significantly blunted in the left servo-controlled kidney compared with the right uncontrolled kidney. The number of CD3(+), CD3(+)CD4(+), and CD3(+)CD8(+) T cells were all significantly lower in the left servo-controlled kidney. This effect was not specific to T cells because CD45R(+) (B cells) and CD11b/c(+) (monocytes and macrophages) cell infiltrations were all exacerbated in the hypertensive kidneys. Increased renal perfusion pressure was also associated with augmented renal injury, with increased protein casts and glomerular damage in the hypertensive kidney. Levels of norepinephrine were comparable between the 2 kidneys, suggestive of equivalent sympathetic innervation. Renal infiltration of T cells was not reversed by the return of renal perfusion pressure to control levels after 7 days of salt-sensitive hypertension. We conclude that increased pressure contributes to the initiation of renal T-cell infiltration during the progression of salt-sensitive hypertension in SS rats. © 2017 American Heart Association, Inc.

  6. Prognostic Significance of CD24 in Clear Cell Renal Cell Carcinoma.

    PubMed

    Arik, Deniz; Can, Cavit; Dündar, Emine; Kabukçuoğlu, Sare; Paşaoğlu, Özgül

    2016-10-13

    The role of cancer stem cells in the initiation and progression of cancer has become a well-studied area of emerging research, and stem cells with different surface markers have been identified in various types of cancer. CD24 is a membrane protein that acts as the ligand for P-selectin and has been defined as a stem cell marker of colonic cancer. The immunohistochemical expression of CD24 is associated with worse patient outcomes in small cell lung cancer, hepatocellular carcinoma, breast cancer, and colon cancer. In this study, we used immunohistochemistry to determine CD24 expression in clear cell, papillary and chromophobe renal cell carcinoma and investigated its relationship with other clinicopathological parameters and prognosis. A total of 108 cases of clear cell, 12 papillary and 13 choromophobe renal cell carcinoma were examined. Clinicopathological features including age, gender, vascular invasion, tumor necrosis, and T stage were recorded. Clinical stage and overall survival and disease-free survival times were recorded. The immunohistochemical expression of CD24 was classified as low or high based on the percentage and intensity of positive staining. CD24 expression was associated with both tumor grade and recurrence rates. The survival analysis revealed that patients with high CD24 expression exhibited significantly lower overall and disease-free survival. Increased expression of CD24 is related to the prognosis of clear cell renal cell carcinoma. This is the first study identifying a strong association between CD24 expression levels and survival. Thus, CD24 expression may aid in predicting prognosis in clear cell renal cell carcinoma.

  7. Systematic Comparative Protein Expression Profiling of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Lichtenfels, Rudolf; Dressler, Sven P.; Zobawa, Monica; Recktenwald, Christian V.; Ackermann, Angelika; Atkins, Derek; Kersten, Michael; Hesse, Andrea; Puttkammer, Maria; Lottspeich, Friedrich; Seliger, Barbara

    2009-01-01

    Proteome-based technologies represent powerful tools for the analysis of protein expression profiles, including the identification of potential cancer candidate biomarkers. Thus, here we provide a comprehensive protein expression map for clear cell renal cell carcinoma established by systematic comparative two-dimensional gel electrophoresis-based protein expression profiling of 16 paired tissue systems comprising clear cell renal cell carcinoma lesions and corresponding tumor-adjacent renal epithelium using overlapping narrow pH gradients. This approach led to the mapping of 348 distinct spots corresponding to 248 different protein identities. By implementing restriction criteria concerning their detection frequency and overall regulation mode, 28 up- and 56 down-regulated single target spots were considered as potential candidate biomarkers. Based on their gene ontology information, these differentially expressed proteins were classified into distinct functional groups and according to their cellular distribution. Moreover, three representative members of this group, namely calbindin, gelsolin, and heart fatty acid-binding protein, were selected, and their expression pattern was analyzed by immunohistochemistry using tissue microarrays. Thus, this pilot study provides a significant update of the current renal cell carcinoma map and defines a number of differentially expressed proteins, but both their potential as candidate biomarkers and clinical relevance has to be further explored in tissues and for body fluids like serum and urine. PMID:19752005

  8. Epidemiology of chronic renal disease in the Galician population: results of the pilot Spanish EPIRCE study.

    PubMed

    Otero, Alfonso; Gayoso, Pilar; Garcia, Fernando; de Francisco, Angel L

    2005-12-01

    Chronic kidney disease (CKD) is a major social health problem because of the aging of the population, the high incidence of diabetes mellitus, and the epidemic of silent CKD resulting from inadequate diagnosis of early chronic renal insufficiency The sociodemographic, baseline characteristics and CKD prevalence measured by the Modification of Diet in Renal Disease formula were studied in a randomly selected sample of people aged 20 years or older in the general population. We report the results of the analysis of the EPIRCE (Estudio Epidemiológico de la Insuficiencia Renal en España) pilot study performed in Galicia, Spain, in the last quarter of 2004. Baseline characteristics, sociodemographic characteristics, and results of a clinical examination and blood variables were collected from 237 patients who fulfilled the study's inclusion and exclusion criteria. The mean age of the sample was 49.58 years (95% confidence interval, 47.39-51.76). The prevalence of Kidney Disease Outcomes Quality Initiative grade 3 CKD was 5.1%, but the coexistence of an albumin/creatinine ratio>30 mg/g with grade 1 to 2 CKD raised the final rate to 12.7% in this population. We found a high prevalence of hypertension (31.5%), isolated systolic hypertension (20.1%), diabetes mellitus (8%), obesity (13.1%), smoking habit (22.7%), high atherogenic index (30.8%), and high alcohol intake (24%). Risk factors significantly associated with renal disease were age [P=0.018; odds ratio (OR) 2.7], hypertension (P=0.023; OR 2.13), pulse pressure (P=0.04; OR 0.10), diabetes mellitus (P=0.08; OR 4.48), obesity (P=0.000; OR 7.7), and insulin resistance index (P=0.04; OR 4.95). The prevalence of CKD and conventional cardiovascular risk factors is high in this randomly selected sample of the general population. Secondary preventive measures are needed to detect chronic kidney impairment as early as possible and to reduce the incidence and mortality arising from the associated comorbidities.

  9. Population pharmacokinetics of cyclosporine A in Japanese renal transplant patients: comprehensive analysis in a single center.

    PubMed

    Okada, Akira; Ushigome, Hidetaka; Kanamori, Misaki; Morikochi, Aya; Kasai, Hidefumi; Kosaka, Tadashi; Kokuhu, Takatoshi; Nishimura, Asako; Shibata, Nobuhito; Fukushima, Keizo; Yoshimura, Norio; Sugioka, Nobuyuki

    2017-09-01

    Cyclosporine A (CyA), a potent immunosuppressive agent used in renal transplantation, has a narrow therapeutic window and a large variability in blood concentrations. This study aimed to develop a population pharmacokinetic (PPK) model of CyA in living-donor renal transplant patients at a single center and identify factors influencing CyA pharmacokinetics (PK). A total of 660 points (preoperative) and 4785 points (postoperative) of blood concentration data from 98 patients who underwent renal transplantation were used. Pre- and postoperative CyA model structure and PPK parameters were separately estimated with a non-linear mixed-effect model, and subsequently, covariate analysis of postoperative data were comprehensively estimated, including preoperative PK parameters. A two-compartment model with first-order absorption and absorption lag time was selected in this study. Aspartate aminotransferase, body surface area (BSA), pretransplant area under the whole blood concentration-time curve/dose, and postoperative days were identified as the covariates on oral clearance. BSA was selected as a covariate of the distribution volume of the central compartment. In addition, diabetes mellitus was selected as a covariate of the first-order absorption rate. This PPK study used the largest number of blood concentration data among previous reports of living-donor renal transplant patients. Moreover, all patients received the same immunosuppressive regimen in a single center. Therefore, the validity of the selected covariates is reliable with high precision. The developed PPK model and selected covariates provide useful information about factors influencing CyA PK and greatly contributes to the identification of the most suitable dosing regimen for CyA.

  10. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    PubMed

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  11. Specific expression of heme oxygenase-1 by myeloid cells modulates renal ischemia-reperfusion injury.

    PubMed

    Rossi, Maxime; Thierry, Antoine; Delbauve, Sandrine; Preyat, Nicolas; Soares, Miguel P; Roumeguère, Thierry; Leo, Oberdan; Flamand, Véronique; Le Moine, Alain; Hougardy, Jean-Michel

    2017-03-15

    Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1(M-KO)), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1(M-KO) exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1(M-KO) mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b(+) F4/80(lo) subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1(+) CD11b(+) F4/80(lo) myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1(M-KO) mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.

  12. Cell cycle progression score predicts metastatic progression of clear cell renal cell carcinoma after resection.

    PubMed

    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.

  13. A study of gizzard nematodes and renal coccidiosis in Canada geese (Branta canadensis interior) of the Mississippi Valley population

    USGS Publications Warehouse

    Tuggle, B.N.

    1982-01-01

    A total of 309 Mississippi Valley Population Canada geese, Branta canadensis interior, of different sex and age groups was collected from three locations in the Mississippi Flyway from 1979-1981 and examined for gizzard nematodes and renal coccidia. Three species of nematodes were removed from the gizzards, Amidostomum anseris, A. spatulatum, and Epomidiostomum crami. The latter two species are reported from this population of geese for the first time. Gizzard nematodes were found in 95.2% of all Canada geese examined, with A. anseris being the most abundant of the three species. There was no statistically significant difference between immatures and adults in the abundance of total nematodes species however, immature geese carried significantly more A. anseris and adult geese harbored significantly more A. spatulatum and E. crami infections. No significant difference in gizzard worm infections between male and female birds was observed. The abundance of overall gizzard nematodes was greatest in Canada geese from Winisk, Ontario (11.9), but the abundance of worms in southern Illinois geese (10.0) was similar. Geese from Horicon National Wildlife Refuge had the lowest abundance of infection, 7.5. The overall abundance of nematodes showed a general increase the second year of the study in each sex and age group and at each collection area. Each of three species of nematodes was responsible for some degree of damage to the gizzard lining and koilin, but E. crami was the most pathogenic of the species recovered. The occurrence of renal coccidiosis in Canada geese of this flyway is reported for the first time; the etiologic agent is Eimeria clarkei. The oocysts and/or endogenous stages of E. clarkei were present in 6.8% of the Canada geese sampled and this was the only species found. Male and female geese showed no significant differences in E. clarkei infections, however, significantly more immature geese than adult geese were infected with this species. A cell

  14. Adjuvant Therapy for Renal Cell Carcinoma: Past, Present, and Future

    PubMed Central

    Pal, Sumanta K.

    2014-01-01

    At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials. PMID:24969163

  15. Serum and urine biomarkers for human renal cell carcinoma.

    PubMed

    Pastore, A L; Palleschi, G; Silvestri, L; Moschese, D; Ricci, S; Petrozza, V; Carbone, A; Di Carlo, A

    2015-01-01

    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.

  16. The somatic genomic landscape of chromophobe renal cell carcinoma

    PubMed Central

    Davis, Caleb F.; Ricketts, Christopher; 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

    Summary We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations. PMID:25155756

  17. The somatic genomic landscape of chromophobe renal cell carcinoma.

    PubMed

    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

    2014-09-08

    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 with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.

  18. Eyelid metastasis as first presentation of renal cell carcinoma.

    PubMed

    Cabrera-Beyrouti, R; Campos-Mollo, E; Rico-Santos, E; Jiménez-Rodríguez, D N; Lledó-Riquelme, M; Vierna-García, J

    2017-01-05

    An 87-year-old male presented with a slow-growing, painless and well defined nodule in the upper eyelid. The tumour measured 1cm, and was pigmented and adhered to deep planes. The histopathology analysis was compatible with renal cell carcinoma. The extension study showed a tumour mass in each kidney, as well as multiple pulmonary metastases. The ophthalmologist can play an important role in the diagnosis of metastatic cancer when eye disease is present. Therefore, the importance of a biopsy should be noted in those suspicious and/or recurrent lesions of the eyelid. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation

    PubMed Central

    Arjunan, Ravi; Kumar, K V Veerendra; Premlatha, C S

    2016-01-01

    Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC. PMID:27891445

  20. EAU guidelines on renal cell carcinoma: 2014 update.

    PubMed

    Ljungberg, Borje; Bensalah, Karim; Canfield, Steven; Dabestani, Saeed; Hofmann, Fabian; Hora, Milan; Kuczyk, Markus A; Lam, Thomas; Marconi, Lorenzo; Merseburger, Axel S; Mulders, Peter; Powles, Thomas; Staehler, Michael; Volpe, Alessandro; Bex, Axel

    2015-05-01

    The European Association of Urology Guideline Panel for Renal Cell Carcinoma (RCC) has prepared evidence-based guidelines and recommendations for RCC management. To provide an update of the 2010 RCC guideline based on a standardised methodology that is robust, transparent, reproducible, and reliable. For the 2014 update, the panel prioritised the following topics: percutaneous biopsy of renal masses, treatment of localised RCC (including surgical and nonsurgical management), lymph node dissection, management of venous thrombus, systemic therapy, and local treatment of metastases, for which evidence synthesis was undertaken based on systematic reviews adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Relevant databases (Medline, Cochrane Library, trial registries, conference proceedings) were searched (January 2000 to November 2013) including randomised controlled trials (RCTs) and retrospective or controlled studies with a comparator arm. Risk of bias (RoB) assessment and qualitative and quantitative synthesis of the evidence were performed. The remaining sections of the document were updated following a structured literature assessment. All chapters of the RCC guideline were updated. For the various systematic reviews, the search identified a total of 10,862 articles. A total of 151 studies reporting on 78,792 patients were eligible for inclusion; where applicable, data from RCTs were included and meta-analyses were performed. For RCTs, there was low RoB across studies; however, clinical and methodological heterogeneity prevented data pooling for most studies. The majority of studies included were retrospective with matched or unmatched cohorts based on single or multi-institutional data or national registries. The exception was for systemic treatment of metastatic RCC, in which several RCTs have been performed, resulting in recommendations based on higher levels of evidence. The 2014 guideline has been updated by

  1. Trial Watch: Therapeutic vaccines in metastatic renal cell carcinoma.

    PubMed

    Combe, Pierre; de Guillebon, Eleonore; Thibault, Constance; Granier, Clémence; Tartour, Eric; Oudard, Stéphane

    2015-05-01

    Despite the renaissance of cancer immunotherapy, no novel immunotherapy has been approved for the treatment of renal cell cancer (RCC) since the availability of recombinant cytokines (interleukin-2, interferon-α). All vaccine trials have failed to meet their endpoints although they have highlighted potential predictive biomarkers (e.g., pre-existing immune response, hematological parameters, tumor burden). Recent advances in immunomodulatory therapies have prompted the study of combination treatments targeting the tumor immunosuppressive microenvironment consisting of regulatory T-cells (Treg), myeloid suppressor cells, and cytokines. Approaches under investigation are use of inhibitors to curb the overexpression of immune checkpoint ligands by tumor cells (e.g., anti-CTLA-4, anti-PD-1/PD-L1) and exploiting the immunomodulatory effects of anti-angiogenic agents that are the current standard of metastatic RCC care. Phase III trials are focusing on the possible synergy between therapeutic vaccines (e.g., IMA-901 and AGS-003) and anti-angiogenic agents.

  2. Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.

    PubMed

    Lau, B H; Ruckle, H C; Botolazzo, T; Lui, P D

    1994-01-01

    Tumors are known to produce factors suppressing immune functions. We previously showed that a murine renal cell carcinoma (Renca) suppressed macrophage function in vitro and that this suppression was abolished by co-incubation with extracts of two Chinese medicinal herbs. We now report that these phytochemicals are capable of inhibiting growth of Renca in vivo. BALB/c mice were transplanted intraperitoneally (IP) with 1-2 x 10(5) Renca cells. One day after tumor transplant, mice were randomized into two groups. One group was treated IP, daily for 10 days, with 100 microliters of phytochemicals containing 500 micrograms each of Astragalus membranaceus and Ligustrum lucidum, while the other group received saline as controls. A cure rate of 57% was obtained with these phytochemicals when the initial tumor load was 2 x 10(5), and 100% when the initial tumor load was 1 x 10(5). Additional experiments were performed to investigate the mechanisms involved in this protection. Splenic macrophages from tumor-bearing mice were shown to have depressed chemiluminescent oxidative burst activity, and this depression was restored with phytochemical treatment. Splenocytes from mice transplanted with Renca responded less favorably to interleukin-2 (IL-2) in generating lymphokine-activated killer (LAK) cells; again this depression was restored with phytochemical treatment. Our data suggest that these phytochemicals may have exerted their antitumor effects via augmentation of phagocyte and LAK cell activities.

  3. Risk models for patients with localised renal cell carcinoma.

    PubMed

    Velis, J M; Ancizu, F J; Hevia, M; Merino, I; García, A; Doménech, P; Algarra, R; Tienza, A; Pascual, J I; Robles, J E

    2017-04-28

    We conducted a retrospective analysis of our series to assess the factors that influenced disease-free survival (DFS) and cancer-specific survival (CSS) for patients with localised renal cell carcinoma (RCC). We also created our own risk groups. Between January 1990 and December 2012, 596 patients underwent surgery for localised RCC (clear cell, papillary or chromophobe). Using Cox regression models, we analysed the clinical-pathological variables that influenced DFS and CSS and designed risk groups for DFS and CSS with the variables. The median follow-up for the series was 5.96 years. By the end of the study, 112 patients (18.8%) had a recurrence of the disease, with DFS rates of 82%, 77% and 72% at 5, 10 and 15 years, respectively. The independent factors that influenced DFS in the multivariate study were the following: A Furhman grade of 3-4, haematuria, lymphocytic or vascular invasion, the presence of tumour necrosis and a disease stage pT3-pT4. Furthermore, by the end of the study, 57 patients (9.6%) died due to renal cancer, with CSS rates of 92%, 86% and 83% at 5, 10 and 15 years, respectively. The independent factors that influenced CSS in the multivariate study were the following: A Furhman grade of 3-4, perinephric fat invasion and the presence of tumour necrosis. Factors in addition to the disease stage pT3-pT4 in patients with localised RCC are important, such as the presence of haematuria and lymphocytic or vascular invasion for DFS. A Furhman grade of 3-4 and the presence of tumour necrosis are especially relevant for DFS and CSS. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. An association between overexpression of DNA methyltransferase 3B4 and clear cell renal cell carcinoma.

    PubMed

    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.

  5. An association between overexpression of DNA methyltransferase 3B4 and clear cell renal cell carcinoma

    PubMed Central

    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

    2017-01-01

    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. PMID:28160561

  6. Inhibin-A and Decorin Secreted by Human Adult Renal Stem/Progenitor Cells Through the TLR2 Engagement Induce Renal Tubular Cell Regeneration.

    PubMed

    Sallustio, Fabio; Curci, Claudia; Aloisi, Alessandra; Toma, Chiara Cristina; Marulli, Elisabetta; Serino, Grazia; Cox, Sharon Natasha; De Palma, Giuseppe; Stasi, Alessandra; Divella, Chiara; Rinaldi, Rosaria; Schena, Francesco Paolo

    2017-08-15

    Acute kidney injury (AKI) is a public health problem worldwide. Several therapeutic strategies have been made to accelerate recovery and improve renal survival. Recent studies have shown that human adult renal progenitor cells (ARPCs) participate in kidney repair processes, and may be used as a possible treatment to promote regeneration in acute kidney injury. Here, we show that human tubular ARPCs (tARPCs) protect physically injured or chemically damaged renal proximal tubular epithelial cells (RPTECs) by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells. tARPCs without toll-like receptor 2 (TLR2) expression or TLR2 blocking completely abrogated this regenerative effect. Only tARPCs, and not glomerular ARPCs, were able to induce tubular cell regeneration process and it occurred only after damage detection. Moreover, we have found that ARPCs secreted inhibin-A and decorin following the RPTEC damage and that these secreted factors were directly involved in cell regeneration process. Polysaccharide synthetic vesicles containing these molecules were constructed and co-cultured with cisplatin damaged RPTECs. These synthetic vesicles were not only incorporated into the cells, but they were also able to induce a substantial increase in cell number and viability. The findings of this study increase the knowledge of renal repair processes and may be the first step in the development of new specific therapeutic strategies for renal repair.

  7. Cancer stem cells are underestimated by standard experimental methods in clear cell renal cell carcinoma

    PubMed Central

    Gedye, Craig; Sirskyj, Danylo; Lobo, Nazleen C.; Meens, Jalna; Hyatt, Elzbieta; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Jewett, Michael A. S.; Ailles, Laurie E.

    2016-01-01

    Rare cancer stem cells (CSC) are proposed to be responsible for tumour propagation and re-initiation and are functionally defined by identifying tumour-initiating cells (TICs) using the xenotransplantation limiting dilution assay (LDA). While TICs in clear cell renal cell carcinoma (ccRCC) appeared rare in NOD/SCID/IL2Rγ−/− (NSG) mice, xenografts formed more efficiently from small tumour fragments, indicating the LDA underestimated ccRCC TIC frequency. Mechanistic interrogation of the LDA identified multiple steps that influence ccRCC TIC quantitation. For example, tissue disaggregation destroys most ccRCC cells, common assays significantly overestimate tumour cell viability, and microenvironmental supplementation with human extracellular factors or pharmacological inhibition of anoikis increase clonogenicity and tumourigenicity of ccRCC cell lines and primary tumour cells. Identification of these previously uncharacterized concerns that cumulatively lead to substantial underestimation of TICs in ccRCC provides a framework for development of more accurate TIC assays in the future, both for this disease and for other cancers. PMID:27121191

  8. The utility of PAX-2 in distinguishing metastatic clear cell renal cell carcinoma from its morphologic mimics: an immunohistochemical study with comparison to renal cell carcinoma marker.

    PubMed

    Gokden, Neriman; Gokden, Murat; Phan, Dan C; McKenney, Jesse K

    2008-10-01

    PAX-2 is a homeogene expressed during kidney development. Although immunohistochemical expression of PAX-2 has been described in a variety of primary renal cell carcinoma (RCC) subtypes and in metastatic RCC, its specificity as a marker of renal lineage in a metastatic setting has not been fully evaluated. In addition, its utility has not been directly compared with the most widely used antibody in this setting, renal cell carcinoma marker (RCCma). We studied PAX-2 expression in metastatic clear cell renal cell carcinoma (CC-RCC) and in a variety of nonrenal neoplasms with clear cytoplasm that may potentially mimic CC-RCC. Archival material from 27 CC-RCCs metastatic to various organs and 50 close morphologic mimics of CC-RCC were retrieved. Immunohistochemistry with PAX-2 and RCCmapi antibodies was performed on each case. Nuclear staining (PAX-2) or membranous staining (RCCma) was scored semiquantitatively. Twenty-three of 27 (85%) metastatic CC-RCCs showed nuclear immunoreactivity for PAX-2, whereas RCCma reactivity was found in 19 of 27 (70%). The immunoprofiles of the metastatic CC-RCC were PAX-2+/RCCma+: 19 of 27 (70%), PAX-2+/RCCma-: 5 of 27 (19%), PAX-2-/RCCma+: 2 of 27 (7%), and PAX-2-/RCCma-: 1 of 27 (4%). Five of the 50 mimics of CC-RCC (10%) had at least focal nuclear reactivity with PAX-2, including 1 of 3 parathyroid carcinomas (33%), 3 of 7 clear cell carcinomas of the ovary (43%), and the 1 clear cell papillary cystadenoma of the epididymis. Membranous RCCma reactivity was identified in 26 of the 50 mimics (52%). We conclude that PAX-2 is a useful marker for distinguishing metastatic CC-RCC from its potential morphologic mimics, but caution must be used in certain differential diagnostic settings where nonrenal tumors such as parathyroid carcinoma, ovarian clear cell carcinoma, and clear cell papillary cystadenoma of the epididymis were shown to express both PAX-2 and RCCma.

  9. Population ecology of heterotypic tumour cell cultures.

    PubMed

    Sega, M; Chignola, R

    2014-10-01

    Here, we propose a population ecology perspective to describe dynamic interplay between human leukaemia and cervical cancer cells growing together in the same environment. MOLT-3 (human T-lymphoblastic leukaemia) and HeLa (human cervical adenocarcinoma) cells were grown together or alone. Living cells were measured using flow cytometry, by counting propidium iodide-negative cells either CD5(+) (MOLT-3) or CD55(+) (HeLa). We developed a mathematical model to take into account possible interactions between cells and among cells and their environmental niches. Model equations were then fitted to growth data. Ecological interactions that require direct cell contact and indirect mechanisms acting on cell niches, successfully modelled cell population growth. Predicted heterotypic adhesion between the two different cell types was demonstrated experimentally. Theoretical ecology can be assayed using human cells and, most importantly, it can provide a conceptual framework to describe and understand evolution of mixed tumour cell populations. © 2014 John Wiley & Sons Ltd.

  10. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice.

    PubMed

    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; Osafune, Kenji

    2015-09-01

    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. 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.

  11. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

    PubMed Central

    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

  12. Renal manifestations of plasma cell dyscrasias: an appraisal from the patients' bedside to the research laboratory.

    PubMed

    Herrera, G A

    2000-06-01

    One of the most prominent features of plasma cell dyscrasias is the frequent occurrence of renal dysfunction. Renal insufficiency is a common finding with elevated serum creatinine in more than 50% of patients with multiple myeloma at the time of diagnosis. Renal failure is the second most common cause of death in myeloma surpassed only by infections. The reasons for renal failure are multifactorial and early accurate diagnosis of the renal alterations may significantly impact morbidity and survival. Renal failure may result from selective glomerular, tubular interstitial, or vascular pathology or from a combination of pathologic events. The disorders associated with plasma cell dyscrasias include those characterized by monoclonal light chain deposition, encompassing AL-amyloidosis, in addition to the less well-characterized entities, such as heavy chain deposition disease and heavy chain amyloidosis. Therefore, it is more accurate to refer to them as monoclonal immunoglobulin deposition diseases. Staining of renal biopsy specimens for kappa and lambda light chains using immunofluorescence techniques and more sophisticated advanced diagnostic techniques such as immunoelectron microscopy permit detailed characterization of the various renal pathologic manifestations. Renal biopsies can identify monoclonal immunoglobulin deposition, and nephrologists have an opportunity to detect an underlying plasma cell dyscrasia early in its clinical course before overt hematologic alterations become manifest and irreversible renal damage has occurred. The overall spectrum of clinical and pathologic manifestations of monoclonal immunoglobulin deposition renal diseases has expanded considerably in recent years. Recent developments in the research arena promise new therapeutic interventions aimed at avoiding or ameliorating renal damage and even promoting reversal of some of the pathologic alterations. Currently, the 5-year survival rate in myeloma is 29% in white patients and 30

  13. Familial Non-VHL Clear Cell Renal Cell Carcinoma

    MedlinePlus

    ... removed and fertilized in a laboratory. When the embryos reach a certain size, one cell is removed ... question. The parents can then choose to transfer embryos which do not have the mutation. PGD has ...

  14. Angiotensin II induces apoptosis in renal proximal tubular cells.

    PubMed

    Bhaskaran, Madhu; Reddy, Krishna; Radhakrishanan, Neetu; Franki, Nicholas; Ding, Guohua; Singhal, Pravin C

    2003-05-01

    ANG II has been demonstrated to play a role in the progression of tubulointerstial injury. We studied the direct effect of ANG II on apoptosis of cultured rat renal proximal tubular epithelial cells (RPTECs). ANG II promoted RPTEC apoptosis in a dose- and time-dependent manner. This effect of ANG II was attenuated by anti-transforming growth factor (TGF)-beta antibody. Moreover, TGF-beta triggered RPTEC apoptosis in a dose-dependent manner. ANG II also enhanced RPTEC expression of Fas and Fas ligand (FasL); furthermore, anti-FasL antibody attenuated ANG II-induced RPTEC apoptosis. In addition, ANG II increased RPTEC expression of Bax, a cell death protein. Both ANG II type 1 (AT(1)) and type 2 (AT(2)) receptor blockers inhibited ANG II-induced RPTEC apoptosis. SB-202190, an inhibitor of p38 MAPK phosphorylation, and caspase-3 inhibitor also attenuated ANG II-induced RPTEC apoptosis. ANG II enhanced RPTEC heme oxygenase (HO)-1 expression. Interestingly, pretreatment with hemin as well as curcumin (inducers of HO-1) inhibited the ANG II-induced tubular cell apoptosis; conversely, pretreatment with zinc protoporphyrin, an inhibitor of HO-1 expression, promoted the effect of ANG II. These results suggest that ANG II-induced apoptosis is mediated via both AT(1) and AT(2) receptors through the generation of TGF-beta, followed by the transcription of cell death genes such as Fas, FasL, and Bax. Modulation of tubular cell expression of HO-1 has an inverse relationship with the ANG II-induced tubular cell apoptosis.

  15. Prognostic significance of metallothionein expression in renal cell carcinoma

    PubMed Central

    Mitropoulos, Dionisios; Kyroudi-Voulgari, Aspasia; Theocharis, Stamatis; Serafetinides, Efraim; Moraitis, Epaminondas; Zervas, Anastasios; Kittas, Christos

    2005-01-01

    Background Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. Patients and methods The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival). Results Positive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. Conclusions The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter. PMID

  16. Nivolumab in renal cell carcinoma: latest evidence and clinical potential

    PubMed Central

    Mazza, Camille; Escudier, Bernard; Albiges, Laurence

    2016-01-01

    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. The strategy of immune checkpoint blockade is to reduce inhibitory signaling and restore the patient’s natural tumor-specific T-cell-mediated immune responses. Nivolumab is the first PD-1 inhibitor to have gained approval for the treatment of patients with metastatic melanoma, squamous and nonsquamous non-small cell lung cancer (NSCLC), Hodgkin disease and recently RCC. In this review, we discuss results from studies of nivolumab in RCC, clinical experience with this agent, and its future development.

  17. Maslinic Acid Inhibits Proliferation of Renal Cell Carcinoma Cell Lines and Suppresses Angiogenesis of Endothelial Cells

    PubMed Central

    Thakor, Parth; Song, Wenzhe; Subramanian, Ramalingam B.; Thakkar, Vasudev R.; Vesey, David A.

    2017-01-01

    Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC) remains a treatment-resistant cancer. As red and processed meat are considered risk factors for RCC, and a vegetable-rich diet is thought to reduce this risk, research into plant-based therapeutics may provide valuable complementary or alternative therapeutics for the management of RCC. Herein, we present the antiproliferative and antiangiogenic effects of maslinic acid, which occurs naturally in edible plants, particularly in olive fruits, and also in a variety of medicinal plants. Human RCC cell lines (ACHN, Caki-1, and SN12K1), endothelial cells (human umbilical vein endothelial cell line [HUVEC]), and primary cultures of kidney proximal tubular epithelial cells (PTEC) were treated with maslinic acid. Maslinic acid was relatively less toxic to PTEC when compared with RCC under similar experimental conditions. In RCC cell lines, maslinic acid induced a significant reduction in proliferation, proliferating cell nuclear antigen, and colony formation. In HUVEC, maslinic acid induced a significant reduction in capillary tube formation in vitro and vascular endothelial growth factor. This study provides a rationale for incorporating a maslinic acid–rich diet either to reduce the risk of developing kidney cancer or as an adjunct to existing antiangiogenic therapy to improve efficacy. PMID:28405545

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

    PubMed

    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.

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

    PubMed Central

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

    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 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 α5β1-integrins in VSMCs. Similar remanent cell traction force was found when cells were pulled with beads coated with β1-integrin antibody (Ha2/5). Activation of β1-integrin with soluble antibody also triggered variations of cell traction force and Ca2+ mobilization, which were abolished by the Src inhibitor. In conclusion, mechanical force transduced by α5β1-integrins triggered a myogenic response-like behavior in isolated renal VSMCs. PMID:23325413

  20. Cytochrome P450 CYP3A in human renal cell cancer

    PubMed Central

    Murray, G I; McFadyen, M C E; Mitchell, R T; Cheung, Y-L; Kerr, A C; Melvin, W T

    1999-01-01

    Renal cell cancer is the main malignant tumour of the kidney and has an increasing incidence. This type of tumour has a poor prognosis and shows intrinsic resistance to several anti-cancer drugs. The CYP3A P450 family, which consists of three closely related forms, is involved in the oxidative activation and deactivation of a variety of carcinogens and several anti-cancer drugs. In this study the presence and cellular localization of CYP3A has been investigated using a combination of immunohistochemistry, immunoblotting and reverse transcriptase polymerase chain reaction (RT-PCR) in renal cell cancer and corresponding normal kidney. CYP3A was consistently expressed in both renal call cancer and in normal kidney. In renal cell cancer, CYP3A was localized to tumour cells and in normal kidney the predominant cellular localization of CYP3A was to proximal tubular epithelial cells. RT-PCR showed that both CYP3A5 mRNA and CYP3A7 mRNA were consistently present in both tumour and normal samples, while CYP3A4 mRNA was present in 65% of tumours and 90% of normal samples. This study indicates that individual members of the CYP3A family are expressed in renal cell cancer. The presence of CYP3A in renal cell cancer might be important in the metabolic potentiation as well as the detoxification of chemotherapeutic agents used to renal cancer. © 1999 Cancer Research Campaign PMID:10206301

  1. Mayer-Rokitansky-Küster-Hauser syndrome accompanied by renal cell carcinoma: a case report.

    PubMed

    Mermerkaya, Murat; Burgu, Berk; Hamidi, Nurullah; Yüksel, Seher; Özçakar, Zeynep B; Sertçelik, Ayşe; Yalçinkaya, Fatoş; Soygür, Tarkan

    2013-10-01

    Mayer-Rokitansky-Küster-Hauser anomaly originates from agenesis of the Müllerian duct including agenesis of the uterus and the vagina because of abnormal development of the uterine ducts. This syndrome may be accompanied by the upper urinary tract anomalies such as unilateral renal agenesis, ectopia of 1 or both kidneys, renal hypoplasia, horseshoe kidney, and hydronephrosis. We report a 16-year-old girl, with unilateral renal agenesis, herniating ovary, and renal cell carcinoma in her solitary kidney, associated with Mayer-Rokitansky-Küster-Hauser syndrome-the first case in the literature to our knowledge.

  2. MicroRNA-148b enhances proliferation and apoptosis in human renal cancer cells via directly targeting MAP3K9.

    PubMed

    Nie, Fang; Liu, Tianming; Zhong, Liang; Yang, Xianggui; Liu, Yunhong; Xia, Hongwei; Liu, Xiaoqiang; Wang, Xiaoyan; Liu, Zhicheng; Zhou, Li; Mao, Zhaomin; Zhou, Qin; Chen, Tingmei

    2016-01-01

    Increasing evidence revealed that miRNAs, the vital regulators of gene expression, are involved in various cellular processes, including cell growth, differentiation, apoptosis and progression. In addition, miRNAs act as oncogenes and/or tumor suppressors. The present study aimed to verify the potential roles of miR148b in human renal cancer cells. miR‑148b was found to be downregulated in human renal cancel tissues and human renal cancer cell lines. Functional studies demonstrated that plasmid‑mediated overexpression of miR‑148b promoted cell proliferation, increased the S‑phase population of the cell cycle and enhanced apoptosis in the 786‑O and OS‑RC‑2 renal cancer cell lines, while it did not appear to affect the total number of viable cells according to a Cell Counting Kit‑8 assay. Subsequently, a luciferase reporter assay verified that miR148b directly targeted mitogen‑activated protein kinase (MAPK) kinase kinase 9 (MAP3K9), an upstream activator of MAPK kinase/c‑Jun N‑terminal kinase (JNK) signaling, suppressing the protein but not the mRNA levels. Furthermore, western blot analysis indicated that overexpression of miR148b in renal cancer cells inhibited MAPK/JNK signaling by decreasing the expression of phosphorylated (p)JNK. In addition, overexpression of MAP3K9 and pJNK was detected in clinical renal cell carcinoma specimens compared with that in their normal adjacent tissues. The present study therefore suggested that miR‑148b exerts an oncogenic function by enhancing the proliferation and apoptosis of renal cancer cells by inhibiting the MAPK/JNK pathway.

  3. Quantitative tumour necrosis is an independent predictor of overall survival in clear cell renal cell carcinoma.

    PubMed

    Renshaw, Andrew A; Cheville, John C

    2015-01-01

    Previous studies have reached conflicting results regarding whether tumour necrosis is a predictor of survival in clear cell renal cell carcinoma. In addition, studies quantifying the extent of necrosis are limited.The aim of this study was to determine if quantifying tumour necrosis could improve its predictive value for survival in clear cell renal cell carcinoma.We reviewed the clinical pathological information contained in The Cancer Genome Atlas for clear cell renal cell carcinoma and correlated it with overall survival using a Cox proportional hazard model. Necrosis was quantified on a single frozen section slide taken at the time of tissue harvesting for molecular studies.For all tumours, the presence of tumour necrosis was a significant predictor of overall survival (p < 0.001) on univariate analysis. When quantitated, >10% necrosis was associated with survival, but ≤10% necrosis was not. On multivariate analysis, age (p = 0.004), T3b stage (p = 0.02), M1 stage (p < 0.001), necrosis >30% (p < 0.001), and elevated serum calcium (p = 0.003) remained significant. For clinical stage 1-2 (T1-T2N0M0) tumours, necrosis >20% was significant on univariate analysis (p ≤ 0.005), and remained so on multivariate analysis (p < 0.001).We conclude that quantitating the extent of tumour necrosis adds prognostic information in clear cell renal cell carcinomas, including organ confined tumours.

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

    PubMed

    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.

  5. PAX-8 expression in renal tumours and distant sites: a useful marker of primary and metastatic renal cell carcinoma?

    PubMed

    Barr, Meaghan L; Jilaveanu, Lucia B; Camp, Robert L; Adeniran, Adebowale J; Kluger, Harriet M; Shuch, Brian

    2015-01-01

    Immunohistochemical stains have greatly improved the diagnostic accuracy of renal cell carcinoma (RCC) for primary and distant tumours. We evaluate a marker that has recently been incorporated in clinical practice, PAX-8, in primary and metastatic RCCs. Two distinct tissue microarrays were used, one consisting of over 334 renal tumours, 294 with adjacent normal kidney and the other with 40 matched nephrectomy and metastatic sites of RCC. PAX-8 expression was assessed by a method of quantitative immunofluorescence. PAX-8 was positive in 96% (146/152) of normal renal tissue and 83% (227/272) of renal tumours. PAX-8 staining was positive in clear cell, papillary and chromophobe tumours in 80% (165/207), 95% (39/41) and 100% (6/6) of samples, respectively. Overall, intensity of PAX-8 expression was significantly higher in RCC metastatic sites than in the primary site (p=0.0047), however, in matched sites there was no statistically significant difference in the proportion of positive versus negative specimens (p=0.274). As the role of molecular markers expands in the diagnostic algorithm, this study confirms that PAX-8 expression is a useful diagnostic marker for RCC. PAX-8 expression was found in the primary tumour and distant sites. Compared with normal tissue and other histological types, clear cell RCC has lower PAX-8 expression and is less frequently positive, therefore, the lack of expression does not exclude a tumour of renal origin. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Renal adenocarcinoma, hepatocellular carcinoma, and pancreatic islet cell carcinoma in a binturong (Arctictis binturong).

    PubMed

    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 with Paraneoplastic Manifestations: Imaging with CT and F-18 FDG PET/CT.

    PubMed

    Nguyen, Ba D; Roarke, Michael C

    2007-01-01

    We present a case of renal cell carcinoma with prominent inflammatory and paraneoplastic manifestations. The initial CT detection of renal malignancy and subsequent post-therapeutic F-18 FDG PET/CT diagnosis of occult osseous metastasis were based on the patient's anemia, thrombocytosis and abnormally increased levels of serum C-reactive protein.

  8. Wnt antagonist DICKKOPF-3 (Dkk-3) induces apoptosis in human renal cell carcinoma.

    PubMed

    Ueno, Koji; Hirata, Hiroshi; Majid, Shahana; Chen, Yi; Zaman, Mohd S; Tabatabai, Z Laura; Hinoda, Yuji; Dahiya, Rajvir

    2011-06-01

    The Wnt signaling pathway is activated in most cancers while Wnt antagonist genes are inactivated. However, the functional significance and mechanisms of inactivation of Wnt antagonist Dkk-3 gene in renal cell carcinoma (RCC) has not been reported. In this study, we examined potential epigenetic mechanisms regulating Dkk-3 expression in RCC cells and whether Dkk-3 expression affects cell growth and apoptosis. The expression of Dkk-3 is regulated by histone modification rather than CpG island DNA methylation in renal cancer cells. Renal cancer cell proliferation was significantly inhibited and apoptosis was promoted in Dkk-3 transfected renal cancer cells. Dkk-3 did not inhibit the Wnt/beta-catenin signaling pathway but induced apoptosis via the noncanonical JNK pathway in renal cancer cells. Expression of p21, MDM-2, and Puma genes were increased after transfecting RCC cell lines with a Dkk-3 expression plasmid. Overexpression of Dkk-3 induced G(0)/G(1) arrest together with an increase in p21 expression. Growth of stable Dkk-3 transfected cells in nude mice was decreased compared to controls. Our data show for the first time that mRNA expression of Dkk-3 is regulated by histone modification and that Dkk-3 inhibits renal cancer growth through modulation of cell cycle and apoptotic pathways.

  9. Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma.

    PubMed

    Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming

    2007-05-18

    Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to beta-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing beta-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells.

  10. Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

    SciTech Connect

    Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming . E-mail: fandaim@fmmu.edu.cn

    2007-05-18

    Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to {beta}-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing {beta}-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells.

  11. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

    PubMed Central

    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.

  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

    PubMed Central

    Alastal, Yaseen; Hammad, Tariq A; Rafiq, Ehsan; Nawras, Mohamad; Alaradi, Osama

    2015-01-01

    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. PMID:28326261

  13. Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation.

    PubMed

    Bilkenroth, U; Taubert, H; Riemann, D; Rebmann, U; Heynemann, H; Meye, A

    2001-05-15

    We have established an immunomagnetic separation procedure for the detection of circulating tumor cells in the peripheral blood based on the magnetic cell sorting (MACS) technique. In previous in vitro experiments, renal-cell carcinoma (RCC) cells were mixed with peripheral blood. In dilutions of 1:200 to 1:107 tumor cells per mononuclear blood cells, an average recovery rate of 84% of tumor cells was determined. In our study, 104 peripheral blood samples from 59 renal carcinoma patients were analyzed. MACS resulted in significant depletion of leukocytes, permitting a search for tumor cells on just 1 slide. Analyzing 8 ml of peripheral blood per patient, 19/59 RCC patients carried disseminated tumor cells (32%) in the range of 1 to 38 cells (median 8). Interestingly, for the cytokeratin-positive (CK+) patient group, we found a correlation between tumor cell number and grading (G2 vs. G3) and an increased number of CK+ patients with advanced tumor stage. MACS appears to be an efficient technique to detect disseminated tumor cells in peripheral blood.

  14. Embolization for Treatment of Gastrointestinal Hemorrhage Secondary to Recurrent Renal Cell Carcinoma

    SciTech Connect

    Kobak, Jeff; Gandras, Eric J. Fleury, Linwald; Macura, Jerzy; Shams, Joseph

    2006-12-15

    Massive gastrointestinal hemorrhage secondary to metastatic renal cell carcinoma involving the jejunum is rare but has been previously described in the medical literature. Treatment options for metastatic renal cell carcinoma are limited, but transcatheter arterial embolization can be performed to control gastrointestinal hemorrhage either alone or prior to surgical resection. We describe a case of successful transcatheter arterial embolization for control of massive gastrointestinal hemorrhage secondary to locally recurrent renal cell carcinoma invading the jejunum and review the literature. Arteriography provided both the diagnosis of recurrent disease and the means of therapy.

  15. Advanced Renal Failure in Patients with Sickle Cell Anemia: Clinical Course and Prognosis

    PubMed Central

    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. Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk.

    PubMed

    Gibson, Todd M; Brennan, Paul; Han, Summer; Karami, Sara; Zaridze, David; Janout, Vladimir; Kollarova, Helen; Bencko, Vladimir; Navratilova, Marie; Szeszenia-Dabrowska, Neonila; Mates, Dana; Slamova, Alena; Pfeiffer, Ruth M; Stolzenberg-Solomon, Rachael Z; Mayne, Susan T; Yeager, Meredith; Chanock, Stephen; Rothman, Nat; Chow, Wong-Ho; Rosenberg, Philip S; Boffetta, Paolo; Moore, Lee E

    2011-01-01

    Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer. Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes. The strongest associations with RCC risk were observed for SLC19A1 (P(min-P) = 0.03) and MTHFR (P(min-P) = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake. To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings.

  17. Comprehensive Evaluation of One-Carbon Metabolism Pathway Gene Variants and Renal Cell Cancer Risk

    PubMed Central

    Gibson, Todd M.; Brennan, Paul; Han, Summer; Karami, Sara; Zaridze, David; Janout, Vladimir; Kollarova, Helen; Bencko, Vladimir; Navratilova, Marie; Szeszenia-Dabrowska, Neonila; Mates, Dana; Slamova, Alena; Pfeiffer, Ruth M.; Stolzenberg-Solomon, Rachael Z.; Mayne, Susan T.; Yeager, Meredith; Chanock, Stephen; Rothman, Nat; Chow, Wong-Ho; Rosenberg, Philip S.; Boffetta, Paolo; Moore, Lee E.

    2011-01-01

    Introduction Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer. Methods Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes. Results The strongest associations with RCC risk were observed for SLC19A1 (Pmin-P = 0.03) and MTHFR (Pmin-P = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake. Conclusions To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings. PMID:22039442

  18. The determination of relative renal function in a pediatric population using Tc-99m DTPA and Tc-99m DMSA

    SciTech Connect

    Rosen, P.R.; Kuruc, A.; Treves, S.T.

    1985-05-01

    Three methods for evaluating relative renal function in a pediatric population were compared. The clinical and nuclear medicine data of 73 patients were reviewed. Pertinent data included patient age, serum creatinine and the referral diagnosis (reflux, hypertension, obstructive uropathy). Time activity curves for renal regions of interest (ROI) were obtained by renography with Tc-99m DTPA, and deconvolved by an externally detected blood pool curve Furosemide was then administered to evaluate the renal collecting system (if indicated). This was followed by DMSA administration. Relative function was determined in 3 ways: 1) Accumulated renal DTPA activity 60-120 sec. following injection. 2) Amplitude of the tubular phase of the deconvolved renal curve and, 3) Accumulated Tc-99m DMSA activity in renal ROI 4 or 24 hrs. post-injection. Regression analysis revealed: 1) The basic relationship of relative functional data obtained by all three methods was not affected by creatinine, age or other factors. 2) The relationship between the three methods is linear and highly correlated. 3) The DMSA values may be predicted from either method of analyzing the DTPA study using appropriate predictor equations. The authors conclude that Tc-99m DMSA, due to its higher cost and more radiation exposure should not be used for the routine evaluation of relative renal function.

  19. Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy.

    PubMed

    Roger, Claire; Wallis, Steven C; Muller, Laurent; Saissi, Gilbert; Lipman, Jeffrey; Lefrant, Jean-Yves; Roberts, Jason A

    2016-08-01

    The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (Cmax)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.).

  20. Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy

    PubMed Central

    Wallis, Steven C.; Muller, Laurent; Saissi, Gilbert; Lipman, Jeffrey; Lefrant, Jean-Yves; Roberts, Jason A.

    2016-01-01

    The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h−1 for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h−1 for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (Cmax)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.) PMID:27270279

  1. Identification and Characterization of Renal Cell Carcinoma Gene Markers

    PubMed Central

    Dalgin, Gul S.; Holloway, Dustin T.; Liou, Louis S.; DeLisi, Charles

    2007-01-01

    Microarray gene expression profiling has been used to distinguish histological subtypes of renal cell carcinoma (RCC), and consequently to identify specific tumor markers. The analytical procedures currently in use find sets of genes whose average differential expression across the two categories differ significantly. In general each of the markers thus identified does not distinguish tumor from normal with 100% accuracy, although the group as a whole might be able to do so. For the purpose of developing a widely used economically viable diagnostic signature, however, large groups of genes are not likely to be useful. Here we use two different methods, one a support vector machine variant, and the other an exhaustive search, to reanalyze data previously generated in our Lab (Lenburg et al. 2003). We identify 158 genes, each having an expression level that is higher (lower) in every tumor sample than in any normal sample, and each having a minimum differential expression across the two categories at a significance of 0.01. The set is highly enriched in cancer related genes (p = 1.6 × 10−12), containing 43 genes previously associated with either RCC or other types of cancer. Many of the biomarkers appear to be associated with the central alterations known to be required for cancer transformation. These include the oncogenes JAZF1, AXL, ABL2; tumor suppressors RASD1, PTPRO, TFAP2A, CDKN1C; and genes involved in proteolysis or cell-adhesion such as WASF2, and PAPPA. PMID:19455236

  2. TroVax(®) vaccine therapy for renal cell carcinoma.

    PubMed

    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.

  3. Targeted therapy for renal cell carcinoma: The next lap

    PubMed Central

    Kanesvaran, Ravindran; Tan, Min-Han

    2014-01-01

    Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR), there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings. PMID:24737951

  4. Cannabinoid CB₁ receptor is downregulated in clear cell renal cell carcinoma.

    PubMed

    Larrinaga, Gorka; Sanz, Begoña; Pérez, Itxaro; Blanco, Lorena; Cándenas, María L; Pinto, Francisco M; Gil, Javier; López, José I

    2010-12-01

    Several studies in cell cultures and in animal models have demonstrated that cannabinoids have important antitumoral properties. Because many of these effects are mediated through cannabinoid (CB) receptors CB₁ and CB₂, the study of their expression in human neoplasms has become of great interest in recent years. Fresh and formalin-fixed tissue samples of 20 consecutive clear cell renal cell carcinomas (CCRCCs) were collected prospectively and analyzed for the expression of both CB receptors by using RT-PCR, Western blot (WB), and immunohistochemical techniques. RT-PCR assays demonstrated the expression of mRNA encoding the CB₁ in tumor tissue and in adjacent non-neoplastic kidney. Conversely, WB and IHC revealed a marked downregulation of CB₁ protein in tumor tissue; CB₂ was not expressed. The obtained data suggest a possible implication of the endocannabinoid system in renal carcinogenesis. A posttranscriptional downregulation of CB₁ and the absence of expression of CB₂ characterize CCRCC.

  5. Glutathione-S-transferase-pi (GST-pi) expression in renal cell carcinoma.

    PubMed

    Kaprilian, Christina; Horti, Maria; Kandilaris, Kosmas; Skolarikos, Andreas; Trakas, Nikolaos; Kastriotis, Ioannis; Deliveliotis, Charalambos

    2015-01-01

    Multidrug resistance correlates with unfavourable treatment outcomes in numerous cancers including renal cell carcinoma. The expression and clinical relevance of Glutathione-S-transferase-pi (GST-pi), a multidrug resistance factor, in kidney tumors remain controversial. We analyzed the expression of GST-pi in 60 formalin-fixed, paraffin-embedded renal cell carcinoma samples by immunohistochemistry and compared them with matched normal regions of the kidney. A significantly higher expression of GST-pi was observed in 87% of clear cell carcinoma and 50% of papillary subtypes. GST-pi expression did not correlate with tumor grade or patient survival. GST-pi is unlikely to be a prognostic factor for renal cell carcinoma. However, further studies with large number of samples are warranted to establish the role of GST-pi, if any, in intrinsic or acquired resistance of renal cell carcinoma to conventional treatments.

  6. Glutathione-S-transferase-pi (GST-pi) expression in renal cell carcinoma

    PubMed Central

    Horti, Maria; Kandilaris, Kosmas; Skolarikos, Andreas; Trakas, Nikolaos; Kastriotis, Ioannis; Deliveliotis, Charalambos

    2015-01-01

    Multidrug resistance correlates with unfavourable treatment outcomes in numerous cancers including renal cell carcinoma. The expression and clinical relevance of Glutathione-S-transferase-pi (GST-pi), a multidrug resistance factor, in kidney tumors remain controversial. We analyzed the expression of GST-pi in 60 formalin-fixed, paraffin-embedded renal cell carcinoma samples by immunohistochemistry and compared them with matched normal regions of the kidney. A significantly higher expression of GST-pi was observed in 87% of clear cell carcinoma and 50% of papillary subtypes. GST-pi expression did not correlate with tumor grade or patient survival. GST-pi is unlikely to be a prognostic factor for renal cell carcinoma. However, further studies with large number of samples are warranted to establish the role of GST-pi, if any, in intrinsic or acquired resistance of renal cell carcinoma to conventional treatments.

  7. Population pharmacokinetics of ganciclovir following administration of valganciclovir in paediatric renal transplant patients.

    PubMed

    Zhao, Wei; Baudouin, Véronique; Zhang, Daolun; Deschênes, Georges; Le Guellec, Chantal; Jacqz-Aigrain, Evelyne

    2009-01-01

    To develop a population pharmacokinetic model for valganciclovir in paediatric renal transplant recipients, identify covariates that explain variability, and determine valganciclovir dosage regimens for cytomegalovirus (CMV) prophylaxis in children. The pharmacokinetics of valganciclovir were described with plasma concentrations from 22 patients (age range 3-17 years) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with lag-time and first-order absorption and elimination was developed. The final model was validated using a bootstrap and visual predictive check. The dosage regimens of valganciclovir for CMV prophylaxis in children were simulated using the final model. The mean population pharmacokinetic parameters were apparent systemic clearance (CL) 10.1L/h, apparent central volume of distribution 5.2 L, apparent peripheral volume of distribution 30.7 L, inter-tissue clearance 3.97 L/h, absorption rate constant 0.369 h-1 and lag-time 0.743 h. The covariate analysis identified creatinine clearance (CL(CR)) and bodyweight (WT) as individual factors influencing the apparent oral clearance: CL= 8.04 x (CL(CR)/89)(2.93) + 3.62 x (WT/28) L/h. The results of the simulation showed that for a typical patient (WT 28 kg and CL(CR) 89 mL/min), an area under the plasma concentration-time curve of 43 +/- 10.6 mg x h/mL will be achieved with valganciclovir 500 mg once daily. The dosage regimens of valganciclovir for CMV prophylaxis have been defined using the final population pharmacokinetic model based on WT and CLCR for paediatric renal transplantation patients.

  8. [RENAL CELL CARCINOMA PRESENTING WITH HIGH-OUTPUT HEART FAILURE DUE TO ARTERIOVENOUS FISTULA].

    PubMed

    Watanabe, Daisuke; Horiguchi, Akio; Isono, Makoto; Sinchi, Masayuki; Masunaga, Ayako; Ito, Keiichi; Asano, Tomohiko

    2015-01-01

    A 64-year-old woman who has a history of congestive heart failure and atrial fibrillation was admitted to our hospital with the exacerbation of exertional dyspnea and urinary retention due to severe gross hematuria. Contrast-enhanced computed tomography showed a tumor involving the inferior and middle poles of the right kidney with no nodal involvement, or distant metastases, but that was accompanied by markedly proliferated blood vessels around the inferior vena cava and right renal vein, seemingly a result of an arteriovenous fistula. After embolization of the right renal artery, right radical nephrectomy was performed via a thoracoabdominal incision. The histological diagnosis of the tumor was clear cell renal cell carcinoma, G2 > G3, Fuhrman nuclear grade3, pT2a. Although the presence of an arteriovenous fistula was not confirmed histologically, the severely condensed proliferation of the blood vessels in the renal hilum is consistent with the diagnosis of an arteriovenous fistula accompanying renal cell carcinoma. Immediately after the operation, her symptoms of congestive heart failure, including dyspnea, subsided and her serum BNP levels and CTR value returned to normal levels. Two years after the operation, she shows no signs of recurrence or metastasis. To the best of our knowledge, there have been 25 cases of arteriovenous fistulas accompanied by renal cell carcinoma but only a few in which the symptoms were those of severe congestive heart failure. Clinicians should be aware that renal cell carcinoima could be a cause of heart failure.

  9. [Angiomyolipoma with epithelioid contingent mimicking renal cell carcinoma].

    PubMed

    Spie, Romain; Devevey, Jean-Marc; Ponnelle, Tibor; Michel, Frédéric

    2005-04-01

    The authors report the case of a patient followed for renal angiomyolipoma. On CT surveillance, this lesion developed features of a malignant tumour with loss of the fatty component and the patient was treated by nephrectomy. Histological examination demonstrated renal angiomyolipoma with an epithelioid contingent. The various aspects of this histological and radiological variant are discussed.

  10. Human CD133+ Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis After Acute Tubular Injury

    PubMed Central

    Aggarwal, Shikhar; Grange, Cristina; Iampietro, Corinne; Camussi, Giovanni; Bussolati, Benedetta

    2016-01-01

    Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133+ renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133+ cells on erythropoietin production. Administration of CD133+ cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133+ cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133+ cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133+ cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis. PMID:27853265

  11. A novel method of estimating cost of therapy by using patient population characteristics: analysis of fluoroquinolones in various populations with different distributions of renal function.

    PubMed

    Enzweiler, Kevin A; Bosso, John A; White, Roger L

    2003-07-01

    Formulary decisions regarding a given drug class are often made in the absence of patient outcome and/or sophisticated pharmacoeconomic data. Analyses that consider factors beyond simple acquisition costs may be useful in such situations. For example, the cost implications of using manufacturers' recommendations for dosing in patients with renal dysfunction may be important, depending on the distribution of various levels of renal function within a patient population. Using four 1000-patient populations representing different renal function distributions and a fifth population of our medical center's distribution, we determined the costs of therapy for intravenous and oral levofloxacin, gatifloxacin, and moxifloxacin for a 10-day course of therapy for community-acquired pneumonia. Costs considered were average wholesale prices (AWPs), 50% of AWP, or same daily price, plus intravenous dose preparation and administration costs when applicable. Costs for each renal function distribution were examined for significant differences with an analysis-of-variance test. Also, costs of failing to adjust dosing regimens for decreased renal function were determined. Differences in fluoroquinolone costs (AWP, 50% AWP, or when matched as the same daily price) among the populations were found. When considering same daily prices, differences among populations ranged from about 35,000 dollars with intravenous gatifloxacin to more than 51,000 dollars for intravenous levofloxacin (all fluoroquinolones, p>0.05). Within a population, differences in costs among the intravenous fluoroquinolones ranged from 47,000-99,000 dollars. Rank orders of the drugs and population costs of therapy were affected by the pricing structure used and varied by the specific population and drug. Differences among the fluoroquinolones or populations were much smaller (<2100 dollars) when considering oral regimens. Costs potentially incurred by failing to adjust dosing for renal function were substantial

  12. LMP2, a novel immunohistochemical marker to distinguish renal oncocytoma from the eosinophilic variant of chromophobe renal cell carcinoma.

    PubMed

    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.

  13. What association exists between hypertension and simple renal cyst in a screened population?

    PubMed

    Hong, S; Lim, J H; Jeong, I G; Choe, J; Kim, C-S; Hong, J H

    2013-09-01

    To assess the impact of simple renal cyst (SRC) on hypertension, we evaluated the prevalence of SRC as well as the relationship between SRC and hypertension. Data were obtained from 29 666 participants who underwent general health screening tests in 2006. Only participants who underwent contrast-enhanced computed tomography or abdominal ultrasonography were included in our study population. We then correlated the clinical characteristics and parameters of hypertension with the presence or absence of renal cysts. Of all the enrolled participants, 5674 (19.2%) had radiologic evidence of SRC, and hypertension was diagnosed in 9865 participants (33.4%). The SRC had a multivariable-adjusted odds ratio (OR) of 1.28 (95% confidence interval (CI), 1.20-1.36) for the presence of hypertension. In study participants with multiple cysts (>1), a large cyst (4 cm in diameter) or a peripheral cyst location, the ORs for the presence of hypertension were 1.31 (95% CI, 1.19-1.44), 1.29 (95% CI, 1.06-1.56) and 1.33 (95% CI, 1.11-1.64), respectively, compared with those for study participants without cyst after adjusting for other variables. We found the presence of SRC to be associated with a significantly increased incidence of hypertension. In addition, the cyst number, size and location are important characteristics of SRC related to hypertension.

  14. The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets†

    PubMed Central

    Pode-Shakked, Naomi; Shukrun, Rachel; Mark-Danieli, Michal; Tsvetkov, Peter; Bahar, Sarit; Pri-Chen, Sara; Goldstein, Ronald S; Rom-Gross, Eithan; Mor, Yoram; Fridman, Edward; Meir, Karen; Simon, Amos; Magister, Marcus; Kaminski, Naftali; Goldmacher, Victor S; Harari-Steinberg, Orit; Dekel, Benjamin

    2013-01-01

    There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated – NCAM1 expressing – “blastema” phenotype, including a capacity to expand and differentiate into the mature renal-like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR-200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets. PMID:23239665

  15. The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets.

    PubMed

    Pode-Shakked, Naomi; Shukrun, Rachel; Mark-Danieli, Michal; Tsvetkov, Peter; Bahar, Sarit; Pri-Chen, Sara; Goldstein, Ronald S; Rom-Gross, Eithan; Mor, Yoram; Fridman, Edward; Meir, Karen; Simon, Amos; Magister, Marcus; Kaminski, Naftali; Goldmacher, Victor S; Harari-Steinberg, Orit; Dekel, Benjamin

    2013-01-01

    There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated-NCAM1 expressing-"blastema" phenotype, including a capacity to expand and differentiate into the mature renal-like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR-200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets.

  16. P53 inhibitor pifithrin-α prevents the renal tubular epithelial cells against injury

    PubMed Central

    Shen, Yun-Lin; Sun, Lei; Hu, Yu-Jie; Liu, Hua-Jie; Kuang, Xin-Yu; Niu, Xiao-Ling; Huang, Wen-Yan

    2016-01-01

    The injury and repair of renal tubular epith