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Sample records for renal cell populations

  1. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

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

    1988-01-01

    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 MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

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

  3. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  4. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  5. Renal cell carcinoma in patient with crossed fused renal ectopia

    Directory of Open Access Journals (Sweden)

    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  6. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  7. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  8. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

    1990-01-01

    The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

  9. Renal cell carcinoma

    Science.gov (United States)

    ... kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney tumor - CT scan Kidney metastases, CT scan Kidney - blood and urine flow References Campbell SC, Lane BR. Malignant renal tumors. In: Wein AJ, Kavoussi LR, Partin AW, ...

  10. Variation in use of targeted therapies for metastatic renal cell carcinoma: Results from a Dutch population-based registry

    International Nuclear Information System (INIS)

    De Groot, S.; Sleijfer, S.; Redekop, W. K.; Oosterwijk, E.; Haanen, J. B. A. G.; Kiemeney, L. A. L. M.; Uyl-de Groot, C. A.

    2016-01-01

    For patients with metastatic renal cell carcinoma (mRCC), targeted therapies have entered the market since 2006. The aims of this study were to evaluate the uptake and use of targeted therapies for mRCC in The Netherlands, examine factors associated with the prescription of targeted therapies in daily clinical practice and study their effectiveness in terms of overall survival (OS). Two cohorts from PERCEPTION, a population-based registry of mRCC patients, were used: a 2008–2010 Cohort (n = 645) and a 2011–2013 Cohort (n = 233). Chi-squared tests for trend were used to study time trends in the use of targeted therapy. Patients were grouped based on the eligibility criteria of the SUTENT trial, the trial that led to sunitinib becoming standard of care, to investigate the use of targeted therapies amongst patients fulfilling those criteria. Multi-level logistic regression was used to identify patient subgroups that are less likely to receive targeted therapies. Approximately one-third of patients fulfilling SUTENT trial eligibility criteria did not receive any targeted therapy (29 % in the 2008–2010 Cohort; 35 % in the 2011–2013 Cohort). Patients aged 65+ years were less likely to receive targeted therapy in both cohorts and different risk groups (odds ratios range between 0.84–0.92); other factors like number of metastatic sites were of influence in some subgroups. Amongst treated patients, there was a decreasing trend in sunitinib use over time (p = 0.0061), and an increasing trend in pazopanib use (p = 0.0005). Targeted therapies have largely replaced interferon-alfa as first-line standard of care. Nevertheless, many eligible patients in Dutch daily practice did not receive targeted therapies despite their ability to improve survival. Reasons for their apparent underutilisation should be examined more carefully. The online version of this article (doi:10.1186/s12885-016-2395-x) contains supplementary material, which is available to authorized users

  11. Renal stem cells: fact or science fiction?

    Science.gov (United States)

    McCampbell, Kristen K; Wingert, Rebecca A

    2012-06-01

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

  12. Renal cell karcinoma trial

    International Nuclear Information System (INIS)

    Werf-Messing, B. van der; Heul, R.O. van der; Ledeboer, R.C.

    1981-01-01

    A total of 174 patients underwent simple nephrectomy in case of clinically operable kidney cancer without demonstrable metastases. Of these 85 received preoperative irradiation to the kidney and the regional lymph nodes (3000-4000 rad in 3-4 weeks). Prognosis was not influenced by preoperative irradiation. The preoperatively assessable prognostic criteria were sex and sedimentation rate: ESR >= 30 and being male worsened prognosis. The clinical T-categories of the UICC were not related to prognosis. Of the microscopic examination of the nephrectomy specimen, renal vein invasion and to a lesser extent a low degree of differentiation appeared to worsen prognosis. The prognostic influence of the P-categories was caused by a higher incidence of renal vein involvement in case of higher P-category. The most important prognostic factors - ESR, renal vein involvement, and sex - were not interrelated. Elective chemotherapy, radiation therapy, and hormone therapy could be considered in certain high-risk groups. (orig.)

  13. A population-based case-control study of occupation and renal cell carcinoma risk in Iowa.

    Science.gov (United States)

    Zhang, Yawei; Cantor, Kenneth P; Lynch, Charles F; Zheng, Tongzhang

    2004-03-01

    A case-control study involving 406 incident cases and 2,434 controls was conducted in Iowa to examine the association between occupational exposures and renal cell carcinoma risk. After adjusting for major confounders, an increased risk was observed for men among mechanics and repairers (odds ratio [OR] 1.9, 95% confidence interval [CI] = 1.2-2.9); assemblers (OR 2.5, 95% CI = 0.8-7.6); automotive dealership and service station employees (OR 1.9, 95% CI = 0.9-3.9); wholesale traders of durable goods (OR 1.5, 95% CI = 0.7-3.2); farm product vendors (OR 4.4, 95% CI = 1.3-15.5); service organization managers (OR 2.2, 95% CI = 1.0-5.1); financial specialists (OR 2.7, 95% CI = 1.0-7.6); sales occupation supervisors (OR 1.8, 95% CI = 1.0-3.3); guards (OR 5.4, 95% CI = 1.4-20.7); and general farm workers (OR 1.9, 95% CI = 1.0-3.7). Among women, an increased risk was found for employees in depository institutions (OR 3.6, 95% CI = 1.1-11.3); colleges and universities (OR 7.6-95% CI = 2.3-25.6); and retail, including those in grocery stores (OR 2.2, 95% CI = 1.0-4.7). Our results indicate that occupational exposures may increase the risk of renal cell carcinoma.

  14. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

  15. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

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

  16. Can bone marrow differentiate into renal cells?

    Science.gov (United States)

    Imai, Enyu; Ito, Takahito

    2002-10-01

    A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

  17. Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Gniadecki, Robert; Hædersdal, Merete

    2016-01-01

    IMPORTANCE: While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. OBJECTIVE: To determine the risk of cutaneous cancer in HSCT recipients...... autologous) from 1999 through 2014, 4789 RTRs from 1976 through 2014, and 10 age- and sex-matched nontransplanted individuals for each of the groups from the background population. Person-years at risk were calculated from the time of study inclusion until first cutaneous cancer. To compare the risk of skin...... cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up...

  18. Renal epithelioid angiomyolipoma presenting clinically as renal cell ...

    African Journals Online (AJOL)

    M.S. Johnson

    a Detroit Medical Center, Michigan State University School of Osteopathic Medicine, Detroit, MI, USA .... Immunohistochemically, the tumor cells stained strongly positive .... [10] Cao Q, Liu F, Xiao P, Tian X, Li B, Li Z. Coexistence of renal.

  19. RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis.

    Science.gov (United States)

    Yang, Lin; Alyasova, Anna; Ye, Dingwei; Ridolfi, Antonia; Dezzani, Luca; Motzer, Robert J

    2018-02-17

    RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients. RECORD-4 enrolled patients with clear cell mRCC into 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines. Patients received everolimus 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. Primary end point was progression-free survival per investigator review. Data cutoff was Sept 1, 2014. Among Asian (n = 55) versus non-Asian (n = 79) patients, 98% versus 84% had good/intermediate MSKCC prognosis; 73% versus 65% were men, and 85% versus 73% were < 65 years of age. All (100%) Asian patients were of Chinese ethnicity. Median duration of exposure was 5.5 mo for Asian and 6.0 mo for non-Asian patients. Among Asian versus non-Asian patients, median progression-free survival (months) was 7.4 versus 7.8 overall, 7.4 versus 4.0 with prior sunitinib, and 5.7 versus 9.2 with prior other anti-VEGFs. Clinical benefit rate was similar between populations: 74.5% (95% CI 61.0-85.3) for Asian patients and 74.7% (95% CI 63.6-83.8) for non-Asian patients. Most patients achieved stable disease as best overall response (Asian, 63.6%; non-Asian, 69.6%). Overall rate of grade 3/4 adverse events appeared similar for Asian (58%) and non-Asian patients (54%). This RECORD-4 subanalysis demonstrated comparable efficacy and adverse event profiles of second-line everolimus in Asian and non-Asian patients. Efficacy and safety outcomes by prior therapy should be interpreted with caution because of small

  20. Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

    DEFF Research Database (Denmark)

    Mitchell, Thomas J.; Turajlic, Samra; Rowan, Andrew

    2018-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the...

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

    Directory of Open Access Journals (Sweden)

    Anna Giovanna Sciancalepore

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

  2. How Kidney Cell Death Induces Renal Necroinflammation.

    Science.gov (United States)

    Mulay, Shrikant R; Kumar, Santhosh V; Lech, Maciej; Desai, Jyaysi; Anders, Hans-Joachim

    2016-05-01

    The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. CT differentiation of infiltrating renal cell carcinoma and renal urothelial tumor

    International Nuclear Information System (INIS)

    Choi, Hyo Kyeong; Goo, Dong Erk; Bang, Sun Woo; Lee, Moon Gyu; Cho, Kyoung Sik; Auh, Yong Ho

    1994-01-01

    It may be difficult to differentiate renal cell carcinoma involving collecting system from renal urothelial tumor invading into renal parenchyma. The purpose of this study was to assess the differences of CT findings between two conditions. CT findings of 5 cases of renal cell carcinoma involving the renal collecting systems and 10 cases of renal urothelial tumors invading the renal parenchyma were compared, and analyzed about the presence or absence of hydronephrosis, normal or abnormal CT nephrogram, renal contour changes due to mass and tentative diagnosis. The diagnoses were confirmed at surgery. Renal cell carcinoma showed hydronephrosis in only 20% and normal CT nephrogram and outward contour bulging in all cases. In contrast, renal urothelial tumor showed hydronephrosis(70%), abnormal CT nephrogram(60%), and preservation of reinform shape(100%). Renal contour changes and CT nephrogram may be useful in distinguishing both disease entities

  4. Metastatic renal cell carcinoma in the nasopharynx.

    Science.gov (United States)

    Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

    2013-01-01

    Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

  5. Metastatic renal cell carcinoma in the nasopharynx

    Directory of Open Access Journals (Sweden)

    Yavuz Atar

    2013-01-01

    Full Text Available Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient′s clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: 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 1 day, 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. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (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 ≤4 cm 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. Conclusion: US-guided percutaneous MWA

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

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yongyan, E-mail: gaoyongyan7@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Department of Ultrasound, The General Hospital of Chinese People’s Armed Police Forces, 69 Yongding Road, Beijing, 100039 (China); Liang, Ping, E-mail: liangping301@hotmail.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Xiaoling, E-mail: 784107477@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Jie, E-mail: 1411495161@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Cheng, Zhigang, E-mail: 13691367317@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Han, Zhiyu, E-mail: hanzhiyu122@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Duan, Shaobo, E-mail: Dustin2662@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Huang, Hui, E-mail: 309hh@sina.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China)

    2016-11-15

    Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: 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 1 day, 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. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (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 ≤4 cm 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. Conclusion: US-guided percutaneous MWA

  8. Papillary renal cell carcinoma in allograft kidney

    International Nuclear Information System (INIS)

    Roy, Catherine; El Ghali, Sofiane; Buy, Xavier; Gangi, Afshin; Lindner, Veronique

    2005-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. Its occurrence in allograft transplanted kidney has not been debated in the literature. We report two pathologically proven cases and discuss the clinical hypothesis for such neoplasms and the aspect on MR images. The paramagnetic effect of the iron associated with an absence of signal coming from calcifications is a plausible explanation for this unusual hypointense appearance on T2-weighted sequence. (orig.)

  9. CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

    International Nuclear Information System (INIS)

    Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

    1994-01-01

    The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

  10. Renal microvascular disease in an aging population: a reversible process?

    Science.gov (United States)

    Futrakul, Narisa; Futrakul, Prasit

    2008-01-01

    Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.

  11. Kidney (Renal Cell) Cancer—Patient Version

    Science.gov (United States)

    Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

  12. CT staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Spina, Juan C.; Garcia, Adriana T.; Rogondino, Jose; Spina, Juan C. h; Vidales, Valeria; Troiani, Guillermo; Iotti, Alejandro; Venditti, Julio

    2002-01-01

    Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

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

    Science.gov (United States)

    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.

  14. Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

    Directory of Open Access Journals (Sweden)

    Hayam Abdel Meguid El Aggan

    2013-09-01

    Full Text Available Introduction: Chronic allograft nephropathy (CAN is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs and mesenchymal stem cells (MSCs. Characterization of HSCs includes their multipotency, expression of typical surface markers such as CD34 and CD45, while characterization of MSC includes their multipotency, expression of typical surface markers such as CD90 and CD105, and the absence of hemopoietic lineage markers. Aim & methods: The aim of the present work was to study the role of bone marrow-derived HSCs and MSCs, renal progenitor cells and SCF in chronic renal allograft nephropathy in relation to renal hemodynamics and histopathological changes. We studied 30 patients with kidney transplantation for more than 6 months, divided into 15 patients with stable serum creatinine and 15 patients who developed CAN. Detection of HSCs and MSCs in the peripheral blood using flow cytometry via detection of CD34, CD45, CD117 and CD106, as well as immunohistochemical detection of CD34, CD133, VEGF and αSMA in transplanted kidney biopsies of patients with CAN were done. Results: There was a significant increase in the levels of SCF, number of peripheral blood HSCs and MSCs in both transplanted patient groups than the controls and they were higher in patients of group Ia than patients of group Ib, (F = 39.73, P < 0.001, (F = 13.28, P < 0.001, (F = 11.94, P < 0.001, respectively and this was accompanied by evident expression of markers of renal repair. Conclusion: Stem cells might have a role in renal regeneration in CAN and this may pave the way toward the use of stem cells in correction of CAN. KEYWORDS

  15. Renal cell carcinoma presenting as mandibular metastasis

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadnia

    2013-01-01

    Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

  16. Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

    Science.gov (United States)

    ... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

  17. [Plasma cell dyscrasias and renal damage].

    Science.gov (United States)

    Pasquali, Sonia; Iannuzzella, Francesco; Somenzi, Danio; Mattei, Silvia; Bovino, Achiropita; Corradini, Mattia

    2012-01-01

    Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

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

    Science.gov (United States)

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

    2016-10-01

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

  19. Cardiac Metastasis in Renal Cell Carcinoma

    African Journals Online (AJOL)

    abp

    2015-10-21

    Oct 21, 2015 ... Metastatic disease of the heart is over twenty times more common than primary heart tumors [1]. They are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Cardiac involvement in renal cell carcinoma (RCC) commonly arises from direct ...

  20. Asymptomatic renal cell carcinoma incidentally detected by abdominal CT

    International Nuclear Information System (INIS)

    Yoneda, Fumio; Miyake, Noriaki; Tsujimura, Haruhiro; Nakajima, Mikio; Akiyama, Hajime

    1987-01-01

    Four cases of renal cell carcinoma that were incidentally detected by abdominal CT are reported. Abdominal CT was performed during gastro-intestinal examination in two patients and for suspected liver disease in the other two. No patient had symptoms of renal cell carcinoma, or hematuria. In all cases, the histopathological diagnosis was renal cell carcinoma of a low stage. (author)

  1. Kidney (Renal Cell) Cancer—Health Professional Version

    Science.gov (United States)

    Kidney cancer has three main types. Renal cell cancer, or renal cell adenocarcinoma, forms in the tubules of the kidney. Transitional cell carcinoma forms in the renal pelvis and ureter. Wilms tumors are common in children. Find evidence-based information on kidney cancer treatment, research, genetics, and statistics.

  2. Renal cell carcinoma and occupational exposure to chemicals in Canada

    Energy Technology Data Exchange (ETDEWEB)

    Hu, J.; Mao, Y.; White, K. [Health Canada, Ottawa, ON (Canada). Population & Public Health Branch

    2002-05-01

    This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in people in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females.

  3. Cutaneous metastasis of bilateral renal cell carcinoma.

    Science.gov (United States)

    Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

    2013-01-01

    Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

  4. Clinical presentation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Rehman, R.A.; Ashraf, S.; Jamil, N.

    2015-01-01

    Most common malignant tumour of the kidney is Renal Cell Carcinoma (RCC) and is known for its unpredictable clinical behaviour. Aetiology and risk factors are not completely understood. Extensive workup is being done in the understanding of the disease, especially to diagnose early and to treat promptly. The objective of this study was to determine the clinical presentation and pathological pattern of RCC. Methods: After approval from ethical committee a retrospective review of records was conducted extending from January 2012 to January 2014 to identify clinical characteristics of renal cell carcinomas. The study included all renal cancer patients presented to Sheikh Zayed Hospital Lahore with in this specified period. The data was retrieved regarding, history, physical examination and necessary investigations such as ultrasonography of abdomen and pelvis and CT scan of abdomen and pelvis. Results: There were total of 50 cases. The male to female ratio was 3:2. Mean age of patients were 52.38 (18-93) years old. Most common clinical presentation was gross haematuria(66%).The mean tumour size was 8.34 (3-24) cm. Tumour histology were clear cell (84%), papillary transitional cell carcinoma (12%) and oncosytoma contributed 4%. Conclusion: We observed that large number of the patients with RCC presented with haematuria and most of them were male. Common pathological type was clear cell carcinoma. (author)

  5. Oncogenic micro-RNAs and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cristina eGrange

    2014-03-01

    Full Text Available Tumor formation is a complex process that occurs in different steps and involves many cell types, including tumor cells, endothelial cells, and inflammatory cells, which interact to promote growth of the tumor mass and metastasization. Epigenetic alterations occurring in transformed cells result in de-regulation of miRNA expression (a class of small non-coding RNA that regulates multiple functions which contributes to tumorigenesis. The specific miRNAs, which have an aberrant expression in tumors, are defined as oncomiRNAs, and may be either over- or under-expressed, but down-regulation is most commonly observed.Renal cell carcinoma is a frequent form of urologic tumor, associated with an alteration of multiple signaling pathways. Many molecules involved in the progression of renal cell carcinomas, such as HIF, VEGF or mTOR, are possible targets of deregulated miRNAs. Within tumor mass, the cancer stem cell population is a fundamental component that promotes tumor growth. The cancer stem cell hypothesis postulates that cancer stem cells have the unique ability to self-renew and to maintain tumor growth and metastasis. Cancer stem cells present in renal cell carcinoma were shown to express the mesenchymal stem cell marker CD105 and to exhibit self-renewal and clonogenic properties, as well as the ability to generate serially transplantable tumors. The phenotype of cancer stem cell has been related to the potential to undergo the epithelial-mesenchymal transition, which has been linked to the expression pattern of tumorigenic miRNAs or down-regulation of anti-tumor miRNAs. In addition, the pattern of circulating miRNAs may allow discrimination between healthy and tumor patients. Therefore, a miRNA signature may be used as a tumor biomarker for cancer diagnosis, as well as to classify the risk of relapse and metastasis, and for a guide for therapy.

  6. Variant anatomy of renal arteries in a Kenyan population.

    Science.gov (United States)

    Ogeng'o, Julius A; Masaki, Charles O; Sinkeet, Simeon R; Muthoka, Johnstone M; Murunga, Acleus K

    2010-01-01

    Variant anatomy of renal arteries is important in renal transplant, vascular reconstruction, and uroradiological procedures. The variations show ethnic and population differences. Data from Africans are scarce and altogether absent for Kenyans. To describe patterns of origin, trajectories and branching of renal arteries in a Kenyan population. Descriptive cross-sectional study conducted in the Department of Human Anatomy, University of Nairobi. Three hundred and fifty six kidneys from 178 cadavers and postmortem specimens were used in the study. Aorta, renal arteries and kidneys were exposed by dissection. Number, trajectories, level of branching, number of branches and point of entry into the kidney were recorded. Data was analyzed using SPSS version 16.0, and presented using macrographs, tables, and bar charts. Additional arteries occurred in 14.3% of the cases. In 82.4% of these, there was one additional artery. Fifty nine point five per cent of the double renal arteries were parallel and 7.1% crossed. Of the 305 single arteries, 76.4% showed hilar, 21.6% prehilar and 2% intraparenchymal branching. In the hilar branching, ladder type was present in 65% and fork type in 35%. Bifurcation and trifurcation were present in 59.6% and 33.1% respectively. Polar arteries were present in 16.9% cases. Over 14% of the Kenyan population may have additional renal arteries while more than 20% show early branching. Several trajectories and hilar branching patterns exist which renal transplant surgeons and radiologists should be aware of to avoid inadvertent vascular injury.

  7. [Renal length measured by ultrasound in adult mexican population].

    Science.gov (United States)

    Oyuela-Carrasco, J; Rodríguez-Castellanos, F; Kimura, E; Delgado-Hernández, R; Herrera-Félix, J P

    2009-01-01

    Renal length estimation by ultrasound is an important parameter in clinical evaluation of kidney disease and healthy donors. Changes in renal volume may be a sign of kidney disease. Correct interpretation of renal length requires the knowledge of normal limits, these have not been described for Latin American population. To describe normal renal length (RL) by ultrasonography in a group of Mexican adults. Ultrasound measure of RL in 153 healthy Mexican adults stratified by age. Describe the association of RL to several anthropometric variables. A total of 77 males and 76 females were scanner. The average age for the group was 44.12 +/- 15.44 years. The mean weight, body mass index (BMI) and height were 68.87 +/- 11.69 Kg, 26.77 +/- 3.82 kg/m2 and 160 +/- 8.62 cm respectively. Dividing the population by gender, showed a height of 166 +/- 6.15 cm for males and 154.7 +/- 5.97 cm for females (p =0.000). Left renal length (LRL) in the whole group was 105.8 +/- 7.56 mm and right renal length (RRL) was 104.3 +/- 6.45 mm (p = 0.000.) The LRL for males was 107.16 +/- 6.97 mm and for females was 104.6 +/- 7.96 mm. The average RRL for males was 105.74 +/- 5.74 mm and for females 102.99 +/- 6.85 mm (p = 0.008.) We noted that RL decreased with age and the rate of decline accelerates alter 60 years of age. Both lengths correlated significantly and positively with weight, BMI and height. The RL was significantly larger in males than in females in both kidneys (p = 0.036) in this Mexican population. Renal length declines after 60 years of age and specially after 70 years.

  8. Cabozantinib (advanced renal cell carcinoma)

    Science.gov (United States)

    ... cancer cells.Cabozantinib is also available as a capsule (Cometriq) to treat a certain type of thyroid ... vomiting material that is bloody or looks like coffee grounds menstrual bleeding that is heavier than usual ...

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

    Science.gov (United States)

    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. 2016 BMJ Publishing Group Ltd.

  10. Metastasis Targeted Therapies in Renal Cell Cancer

    OpenAIRE

    K. Fehmi Narter; Bora Özveren

    2018-01-01

    Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

  11. Comparison of para-aminophenol cytotoxicity in rat renal epithelial cells and hepatocytes.

    Science.gov (United States)

    Li, Ying; Bentzley, Catherine M; Tarloff, Joan B

    2005-04-01

    Several chemicals, including para-aminophenol (PAP), produce kidney damage in the absence of hepatic damage. Selective nephrotoxicity may be related to the ability of the kidney to reabsorb filtered water, thereby raising the intraluminal concentration of toxicants and exposing tubular epithelial cells to higher concentrations than would be present in other tissues. The present experiments tested the hypothesis that hepatocytes and renal epithelial cells exposed to equivalent concentrations of PAP would be equally susceptible to toxicity. Hepatocytes and renal epithelial cells were prepared by collagenase digestion of tissues obtained from female Sprague-Dawley rats. Toxicity was monitored using trypan blue exclusion, oxygen consumption and ATP content. We measured the rate of PAP clearance and formation of PAP-glutathione conjugate by HPLC. We found that renal epithelial cells accumulated trypan blue and showed declines in oxygen consumption and ATP content at significantly lower concentrations of PAP and at earlier time points than hepatocytes. The half-life of PAP in hepatocyte incubations was significantly shorter (0.71+/-0.07 h) than in renal epithelial cell incubations (1.33+/-0.23 h), suggesting that renal epithelial cells were exposed to PAP for longer time periods than hepatocytes. Renal epithelial cells formed significantly less glutathione conjugates of PAP (PAP-SG) than did hepatocytes, consistent with less efficient detoxification of reactive PAP intermediates by renal epithelial cells. Finally, hepatocytes contained significant more reduced glutathione (NPSH) than did renal epithelial cells, possibly explaining the enhanced formation of PAP-SG by this cell population. In conclusion, our data indicates that renal epithelial cells are intrinsically more susceptible to PAP cytotoxicity than are hepatocytes. This enhanced cytotoxicity may be due to longer exposure to PAP and/or reduced detoxification of reactive intermediates due to lower concentrations

  12. Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

    Science.gov (United States)

    Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

    2017-07-01

    Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

  13. Renal abscess in a child with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Taksande Amar

    2009-01-01

    Full Text Available Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

  14. Renal abscess in a child with sickle cell anemia

    OpenAIRE

    Taksande Amar; Vilhekar K

    2009-01-01

    Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

  15. Renal abscess in a child with sickle cell anemia.

    Science.gov (United States)

    Taksande, Amar M; Vilhekar, K Y

    2009-03-01

    Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

  16. Renal abscess in a child with sickle cell anemia

    International Nuclear Information System (INIS)

    Taksande, Amar M; Vilhekar, KY

    2009-01-01

    Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess. (author)

  17. Metallothionein gene expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Deeksha Pal

    2014-01-01

    Full Text Available Introduction: Metallothioneins (MTs are a group of low-molecular weight, cysteine-rich proteins. In general, MT is known to modulate three fundamental processes: (1 the release of gaseous mediators such as hydroxyl radical or nitric oxide, (2 apoptosis and (3 the binding and exchange of heavy metals such as zinc, cadmium or copper. Previous studies have shown a positive correlation between the expression of MT with invasion, metastasis and poor prognosis in various cancers. Most of the previous studies primarily used immunohistochemistry to analyze localization of MT in renal cell carcinoma (RCC. No information is available on the gene expression of MT2A isoform in different types and grades of RCC. Materials and Methods: In the present study, total RNA was isolated from 38 histopathologically confirmed cases of RCC of different types and grades. Corresponding adjacent normal renal parenchyma was taken as control. Real-time polymerase chain reaction (RT PCR analysis was done for the MT2A gene expression using b-actin as an internal control. All statistical calculations were performed using SPSS software. Results: The MT2A gene expression was found to be significantly increased (P < 0.01 in clear cell RCC in comparison with the adjacent normal renal parenchyma. The expression of MT2A was two to three-fold higher in sarcomatoid RCC, whereas there was no change in papillary and collecting duct RCC. MT2A gene expression was significantly higher in lower grade (grades I and II, P < 0.05, while no change was observed in high-grade tumor (grade III and IV in comparison to adjacent normal renal tissue. Conclusion: The first report of the expression of MT2A in different types and grades of RCC and also these data further support the role of MT2A in tumorigenesis.

  18. ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice

    International Nuclear Information System (INIS)

    Okumura, Yasuko; Sugiyama, Noriyuki; Tanimura, Susumu; Nishida, Masashi; Hamaoka, Kenji; Kohno, Michiaki; Yokoyama, Takahiko

    2009-01-01

    Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage kidney disease in children and young adults. Inv mice are a model for human nephronophthisis type 2 (NPHP2) and characterized by multiple renal cysts and situs inversus. Renal epithelial cells in inv cystic kidneys show increased cell proliferation. We studied the ERK pathway to understand the mechanisms that induce cell proliferation and renal cyst progression in inv kidneys. We studied the effects of ERK suppression by administering PD184352, an oral mitogen-activated protein kinase kinase (MEK) inhibitor on renal cyst expansion, extracellular signal-regulated protein kinase (ERK) activity, bromo-deoxyuridine (BrdU) incorporation and expression of cell-cycle regulators in invΔC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invΔC kidneys. PD184352 successfully decreased p-ERK level and inhibited renal cyst enlargement. The inhibitor also decreased expression of cell-cycle regulators and BrdU incorporation in renal epithelial cells. The present results showed that ERK regulated renal cell proliferation and cyst expansion in inv mutants

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

    Science.gov (United States)

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    A.-S. Paşca

    2013-10-01

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

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

    International Nuclear Information System (INIS)

    Ferda, Jiri; Hora, Milan; Hes, Ondrej; Reischig, Tomas; Kreuzberg, Boris; Mirka, Hynek; Ferdova, Eva; Ohlidalova, Kristyna; Baxa, Jan; Urge, Tomas

    2007-01-01

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

  2. Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database.

    Science.gov (United States)

    Daugherty, Michael; Blakely, Stephen; Shapiro, Oleg; Vourganti, Srinivas; Mollapour, Mehdi; Bratslavsky, Gennady

    2016-04-01

    The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p renal cell cancer remained the most common type of nonclear renal cell cancer. It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. The Contemporary Incidence and Sequelae of Rhabdomyolysis Following Extirpative Renal Surgery: A Population Based Analysis.

    Science.gov (United States)

    Gelpi-Hammerschmidt, Francisco; Tinay, Ilker; Allard, Christopher B; Su, Li-Ming; Preston, Mark A; Trinh, Quoc-Dien; Kibel, Adam S; Wang, Ye; Chung, Benjamin I; Chang, Steven L

    2016-02-01

    We evaluate the contemporary incidence and consequences of postoperative rhabdomyolysis after extirpative renal surgery. We conducted a population based, retrospective cohort study of patients who underwent extirpative renal surgery with a diagnosis of a renal mass or renal cell carcinoma in the United States between 2004 and 2013. Regression analysis was performed to evaluate 90-day mortality (Clavien grade V), nonfatal major complications (Clavien grade III-IV), hospital readmission rates, direct costs and length of stay. The final weighted cohort included 310,880 open, 174,283 laparoscopic and 69,880 robotic extirpative renal surgery cases during the 10-year study period, with 745 (0.001%) experiencing postoperative rhabdomyolysis. The presence of postoperative rhabdomyolysis led to a significantly higher incidence of 90-day nonfatal major complications (34.7% vs 7.3%, p rhabdomyolysis (incidence risk ratio 1.83, 95% CI 1.56-2.15, p rhabdomyolysis (vs laparoscopic approach, OR 2.43, p rhabdomyolysis (p rhabdomyolysis developing. Our study confirms that postoperative rhabdomyolysis is an uncommon complication among patients undergoing extirpative renal surgery, but has a potentially detrimental impact on surgical morbidity, mortality and costs. Male gender, comorbidities, obesity, prolonged surgery (more than 5 hours) and a robotic approach appear to place patients at higher risk for postoperative rhabdomyolysis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

    Science.gov (United States)

    Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

    2013-01-01

    Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...

  6. Unilateral Renal Cell Carcinoma in a Dog

    Directory of Open Access Journals (Sweden)

    J. Y. Chung

    2014-01-01

    Full Text Available A 4-year-old, neutered male, American Cocker Spaniel weighing 8.3 kg was presented with a 1-month history of weight-loss, anorexia, intermittent vomiting and bloody-diarrhea. Abnormal blood tests results, a large mass on the kidney field in radiographic views and ultrasonography were presented. Nephroureterectomy was tried, but a large mass in the kidney and metastasis to the spleen caused to decline the surgery and treatment. The dog was euthanized, and necropsy and histological review revealed the renal cell carcinoma.

  7. CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

    Science.gov (United States)

    Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

    2016-08-01

    Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    B. T. Dzumabaeva

    2011-01-01

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

  9. Renal angiographic and computed tomographic evaluation of local extension of renal cell carcinoma

    International Nuclear Information System (INIS)

    Masuda, Fujio; Onishi, Tetsuro; Sasaki, Tadamasa; Arai, Yoshikazu; Shoji, Ryo

    1981-01-01

    In 23 cases of renal cell carcinoma, the degree of local invasion of carcinoma was diagnosed using renal angiography and CT, and compared with the findings obtained by operation or autopsy. Among 5 cases in which the tumor was confined to the renal capsule, accurate diagnosis could be established with renal angiography in 4 cases and with CT in all of 5 cases. Both renal angiography and CT provided correct diagnosis in 7 of 8 cases in which the tumor showed infiltration extending to the perinephric fat. Out of 5 cases with tumor invasion of renal vein or inferior vena cava, diagnosis could be established correctly by renal angiography and CT in 3 cases. Among the remaining 2 cases the diagnosis could be established by renal angiography and CT in one each case. Among 5 cases with metastases to the regional lymph nodes, diagnosis could be established by renal angiography in only 2 cases, while all of 5 cases could be diagnosed by CT. In 3 cases where the tumor invaded an ajacent organ beyond Gerota's fastia, renal angiography could diagnose in none of the 3 cases while with CT all of 3 cases could successfully be diagnosed. The consistency of degree of local invasion as revealed by renal angiography and CT was seen in 15 of 23 cases (65%) for renal agniography and 20 of 23 cases (87%) for CT, indicating superiority of CT in this respect. In particular, CT appears to be more superior to renal angiography for determining whether the tumor confined to Gerota's fastia or it infiltrated over it. Both combined use of renal angiography and CT, the degree of infiltration of tumor could be diagnosed correctly in 22 of 23 cases (96%). (author)

  10. Wnt Signaling in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-06-01

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

  11. Synchronous presentation of nasopharyngeal and renal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Cem Boruban

    2006-06-01

    Full Text Available We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.

  12. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Ruiz-Morales, Jose Manuel; Swierkowski, Marcin; Wells, J Connor

    2016-01-01

    BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International mR...

  13. Sequential Therapy in Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bradford R Hirsch

    2016-04-01

    Full Text Available 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.

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

    Science.gov (United States)

    Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai 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.).

  15. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

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

    2016-01-01

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

  16. Is renal medullary carcinoma the seventh nephropathy in sickle cell ...

    African Journals Online (AJOL)

    Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption. Objective: To estimate the prevalence of RMC and describe other renal ...

  17. Clinical and pathological features of papillary renal cell carcinoma ...

    African Journals Online (AJOL)

    Introduction and objectives: Papillary renal cell carcinoma (PRCC) accounts for 10–15% of renal tumors in adults. This type of tumor contains more than 75% of tubulo-papillary structures and is divided histologically into two subtypes. The distinction between these two subtypes is essential because of their prognostic value.

  18. Prevalence of silent gastrointestinal complications in maintenance renal transplant population

    Directory of Open Access Journals (Sweden)

    Teplitsky Susan

    2010-01-01

    Full Text Available This study aims to determine the prevalence of silent GI complications within a stable renal transplant population and to investigate whether the conversion to enteric-coated myco-phenolate sodium (EC-MPS, Myfortic; would improve symptom scores. This was a single-center, open-label, non-randomized, prospective study. Patients without any history of GI com-plaints were evaluated by means of the gastrointestinal symptom rating scale (GSRS, with subse-quent switch to EC-MPS in a group of patients. Silent complications were defined as patients who voiced no GI complaints at clinic visits despite a score of ≥ 2 on GSRS scale. A total of 236 stable patients participated in the trial. The prevalence of baseline scores ≥ 2 was relatively high with abdominal pain 29.66%, reflux 37.28%, indigestion 50%, constipation 58.47% and diarrhea 33.4%. Of 236 patients, 80 were converted to EC-MPS. There was statistically significant improvement on all scales in the subgroup of patients with GSRS score ≥ 2 (P< 0.05. In conclusion, the GSRS scale identified a high percentage of silent gastrointestinal complications in this renal transplant population. The converted patients with higher GSRS scores reported a sustained improvement.

  19. Magnetic resonance imaging in the staging of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

    1987-07-01

    Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma.

  20. Magnetic resonance imaging in the staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

    1987-01-01

    Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma. (author)

  1. Hematopoietic stem cell mobilization therapy accelerates recovery of renal function independent of stem cell contribution

    NARCIS (Netherlands)

    Stokman, Geurt; Leemans, Jaklien C.; Claessen, Nike; Weening, Jan J.; Florquin, Sandrine

    2005-01-01

    Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in renal pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells in the regeneration of renal tissue after injury. This study investigated whether the enhanced availability

  2. Diagnosis of renal cell cancer by dynamic MRI

    International Nuclear Information System (INIS)

    Togami, Izumi; Kitagawa, Takahiro; Katoh, Katsuya

    1992-01-01

    Dynamic MRI was performed in 15 cases (16 lesions) of renal cell cancer. The enhanced pattern of the tumor was mainly evaluated and findings were compared with these of dynamic CT and renal angiography. Enhanced patterns on dynamic MRI and dynamic CT were similar, but each phase on dynamic MRI tended to be prolonged compared with dynamic CT. Many hypervascular tumors on renal angiography had prominent enhancement in an early phase on dynamic MRI, but there was no prominent enhancement in cases with tumor thrombi in the renal vein or IVC. All hypovascular tumors were enhanced to some degree without exception on dynamic MRI. Dynamic MRI is considered to be useful for the evaluation of the characterization, especially vascularity, of renal cell cancer, but we should pay attention to the differential diagnosis from other tumor in atypical cases because its enhanced patterns are various on dynamic MRI. (author)

  3. [Immunotherapy for renal cell carcinoma - current status].

    Science.gov (United States)

    Grimm, Marc-Oliver; Foller, Susan

    2018-04-01

    Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo ® ) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable toxicity profile compared with Everolimus. Currently, numerous combinations with PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC. Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42 % vs. 27 %, p < 0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib. However, a considerable increase of immune related adverse events is associated with the immune combination therapy. Another randomized trial demonstrates improved progression-free survival for the combination of the PD-L1 inhibitor Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new" VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor Nivolumab will remain a standard treatment for patients with metastatic renal cell carcinoma

  4. Alteraciones renales en la drepanocitosis Renal disorders in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Aramís Núñez-Quintana

    2011-06-01

    Full Text Available La drepanocitosis está asociada con un amplio espectro de alteraciones renales que tienen su base en la falciformación de los eritrocitos en los vasos de la médula renal, que conduce a fenómenos de isquemia, microinfartos y anomalías de la función tubular. Se producen también alteraciones glomerulares funcionales reversibles de la autorregulación renal (hiperfiltración, que pueden conducir a cambios anatómicos irreversibles con glomeruloesclerosis segmentaria focal. Estas anomalías se expresan tempranamente como microalbuminuria, proteinuria y de forma mas tardía, como síndrome nefrótico e insuficiencia renal crónica. Medidas terapéuticas como el uso de inhibidores de la enzima convertidora de la angiotensina II, de los bloqueadores del receptor de la angiotensina II, asociados o no con la hidroxiurea, pueden prevenir o retardar el daño glomerular. En el presente trabajo se exponen de forma resumida aspectos relacionados con la fisiopatología del daño renal en la drepanocitosis y su tratamiento.Sickle cell disease is associated with a wide range of renal disorders resulting from the falciformation of erythrocytes in vessels of the renal medulla, leading to ischemia, microinfarctions and tubular function abnormalities. Reversible glomerular functional renal self-regulation disorders (hyperfiltration also occur, which may lead to irreversible anatomical changes with focal segmental glomerular sclerosis. These anomalies are expressed at an early stage as microalbuminuria and proteinuria, and at a later stage as nephrotic syndrome and chronic renal failure. Therapeutic measures such as the use of angiotensin-II converting enzyme inhibitors and angiotensin-II receptor blockers, associated or not with hydroxyurea, may either prevent or delay glomerular damage. The paper succinctly presents the physiopathology of renal damage in drepanocytosis and its treatment.

  5. A case of renal cell carcinoma and angiomyolipoma in an ...

    African Journals Online (AJOL)

    Abstract. We describe a case of renal cell carcinoma in the right kidney together with an angiomyolipoma in the left kidney, encountered in an adolescent girl at Potchefstroom Provincial Hospital, North West Province, South Africa.

  6. Simultaneous Infiltration of Polyfunctional Effector and Suppressor T Cells into Renal Cell Carcinomas

    NARCIS (Netherlands)

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

    2009-01-01

    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

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

    International Nuclear Information System (INIS)

    Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-15

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  10. Chronic lymphocytic lymphoma and concomitant renal cell carcinoma (Clear Cell Type: Review of the literature

    Directory of Open Access Journals (Sweden)

    Burak Uz

    2016-01-01

    Full Text Available In the present report, a 73 years-old male patient who developed clear cell type renal cell carcinoma (RCC 5 years after the diagnosis of chronic lymphocytic lymphoma (CLL and plausible explanations for this association were discussed by the authors. The incidence of CLL and RCC occurring in the same patient is higher than that expected in the general population. Various explicative hypotheses of this concurrence include treatment-related development of a second malignancy, immunomodulatory mechanisms, viral aetiology, cytokine (interleukin 6 release from a tumor, and common genetic mutations. Further investigations are warranted.

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

    OpenAIRE

    Turker Acar; Mustafa Harman; Serkan Guneyli; Sait Sen; Nevra Elmas

    2014-01-01

    Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this...

  12. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Hoti Lal

    2015-11-01

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

  14. Renal amyloidosis in a child with sickle cell anemia.

    Science.gov (United States)

    Simşek, Behçet; Bayazit, Aysun K; Ergin, Melek; Soran, Mustafa; Dursun, Hasan; Kilinc, Yurdanur

    2006-06-01

    The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.

  15. Gonadal vein tumor thrombosis due to renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hamidreza Haghighatkhah

    2015-01-01

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

  16. Magnetic resonance imaging of large chromophobe renal cell carcinomas

    International Nuclear Information System (INIS)

    Sasaguri, Kohei; Irie, Hiroyuki; Kamochi, Noriyuki; Nakazono, Takahiko; Yamaguchi, Ken; Uozumi, Jiro; Kudo, Sho

    2010-01-01

    The objective of this study was to clarify the magnetic resonance imaging (MRI) findings of large chromophobe renal cell carcinomas. Five patients diagnosed pathologically with chromophobe renal cell carcinoma are included. MRI findings were retrospectively evaluated for the tumor contour, uniformity and hypointensity of the rim of the tumor on T2-weighted images, ''micro-scopic fat'', enhancement degree and pattern on dynamic study, and necrosis in the tumor, among other findings. The tumor size ranged from 4.8 to 13.7 cm (mean 7.9 cm). The tumor contour was well defined in four patients. All but one tumor showed a hypointensity rim, and all tumors had a heterogeneous appearance on T2-weighted images. ''Microscopic fat'' was detected in one case. All tumors demonstrated low enhancement compared to that of the renal cortex. All tumors showed heterogeneous enhancement on postcontrast images. Necrosis was seen in four. Hemorrhage and renal vein thrombosis was seen in one. Chromophobe renal cell carcinomas of large size tend to have a heterogeneous appearance on post-contrast and T2-weighted images, a well-defined tumor contour with a hypointensity rim on T2-wighted images, and lower enhancement than that of the renal cortex. Tumor necrosis is easily apparent, and ''microscopic fat'' may be observed. (author)

  17. Trigeminal perineural spread of renal cell carcinoma

    International Nuclear Information System (INIS)

    Hornik, Alejandro; Rosenblum, Jordan; Biller, Jose

    2012-01-01

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

  18. Renal epithelial cells can release ATP by vesicular fusion

    Directory of Open Access Journals (Sweden)

    Randi G Bjaelde

    2013-09-01

    Full Text Available Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30, which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1 cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin reduced both the spontaneous and hypotonically (80%-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1 and vesicular transport (nocodazole. These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ∼90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50% or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8% and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells.

  19. Characterizing the outcomes of metastatic papillary renal cell carcinoma

    DEFF Research Database (Denmark)

    Connor Wells, John; Donskov, Frede; Fraccon, Anna P

    2017-01-01

    Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were...... compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer...

  20. The effects of renal transplantation on circulating dendritic cells

    NARCIS (Netherlands)

    D.A. Hesselink (Dennis); L.M.B. Vaessen (Leonard); W.C.J. Hop (Wim); W. Schoordijk-Verschoor (Wenda); J.N.M. IJzermans (Jan); C.C. Baan (Carla); W. Weimar (Willem)

    2005-01-01

    textabstractThe effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in

  1. Vitamin E Intake and Risk of Renal Cell Carcinoma: A Meta-Analysis of 7 Case-Control Studies.

    Science.gov (United States)

    Shang, Yonggang; Yi, Shanhong; Cui, Dong; Han, Guangwei; Liu, Chengcheng

    2015-07-01

    Vitamin E intake may reduce the risk of renal cell carcinoma, but the results were inconsistent. Hence, we conducted a meta-analysis to assess the association between dietary vitamin E intake and the risk of renal cell carcinoma. We searched PubMed to identify the relevant case-control studies up to June 2014. Reference lists of retrieved articles were also reviewed. Odds ratios and corresponding 95% confidence intervals were used to estimate the association between dietary vitamin E intake and the risk of renal cell carcinoma. We identified 7 case-control studies regarding dietary vitamin E intake and risk of renal cell carcinoma, involving 5789 cases and 14866 controls. The odds ratio of renal cell carcinoma for the highest compared with the lowest dietary vitamin E intake was 0.75 (95% confidence interval: 0.59-0.91), and heterogeneity was observed across studies. The association between dietary vitamin E intake and the risk of renal cell carcinoma was not significantly differed by gender, but this association were inconsistent in the North American and European populations. Our study provided a evidence that there was a significant inverse association of dietary vitamin E intake with risk of renal cell carcinoma. However, this finding was based on the case-control studies, more well-designed cohort studies are needed. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  2. Image-guided radiofrequency ablation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Boss, Andreas; Clasen, Stephan; Pereira, Philippe L.; Kuczyk, Markus; Schick, Fritz

    2007-01-01

    The incidence of renal cell carcinoma is rising with the increased number of incidental detection of small tumours. During the past few years, percutaneous imaging-guided radiofrequency ablation has evolved as a minimally invasive treatment of small unresectable renal tumours offering reduced patient morbidity and overall health care costs. In radiofrequency ablation, thermal energy is deposited into a targeted tumour by means of a radiofrequency applicator. In recent studies, radiofrequency ablation was shown to be an effective and safe modality for local destruction of renal cell carcinoma. Radiofrequency applicator navigation can be performed via ultrasound, computed tomography or magnetic resonance guidance; however, ultrasound seems less favourable because of the absence of monitoring capabilities during ablation. On-line monitoring of treatment outcome can only be performed with magnetic resonance imaging giving the possibility of eventual applicator repositioning to ablate visible residual tumour tissue. Long-term follow-up is crucial to assess completeness of tumour ablation. New developments in ablation technology and radiological equipment will further increase the indication field for radiofrequency ablation of renal cell carcinoma. Altogether, radiofrequency ablation seems to be a promising new modality for the minimally invasive treatment of renal cell carcinoma, which was demonstrated to exhibit high short-term effectiveness. (orig.)

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

    Science.gov (United States)

    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 cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p 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 cell level correlated positively with the number of patient colonies (r = 0.762, p 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 cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma. Copyright © 2015 American Urological Association Education and Research

  4. Multilocular cystic renal cell carcinoma: imaging and clinical correlation

    International Nuclear Information System (INIS)

    Xu Yong; Zhang Sheng

    2013-01-01

    Multilocular cystic renal cell carcinoma (MCRCC) is a subtype of clear cell renal cell carcinoma and has mild clinical symptoms and a favorable prognosis. Accordingly, nephron-sparing surgery is recommended as a therapeutic strategy. If histologic subtype of MCRCC can be predicted preoperatively with an acceptable level of accuracy, it may be important in predicting prognosis and make clinical management. Most MCRCCs show characteristic cross-sectional imaging findings and permit accurate diagnosis before the treatment. Cross -sectional imaging of MCRCC reveals a well -defined multilocular cystic mass with irregularly enhanced thickened septa and without enhanced intracystic solid nodule. It is often classified as Bosniak classification Ⅲ , which is significantly different from that of other renal cystic masses. The clinical, pathologic, and radiologic features of MCRCC were discussed and illustrated in this article. The role of the imaging preoperative evaluation for MCRCC, and management implications were emphasized. (authors)

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

    International Nuclear Information System (INIS)

    Kim, Cherry; Choi, Hyuck Jae; Cho, Kyoung-Sik

    2014-01-01

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

  6. Renal cells activate the platelet receptor CLEC-2 through podoplanin

    Science.gov (United States)

    Christou, Charita M.; Pearce, Andrew C.; Watson, Aleksandra A.; Mistry, Anita R.; Pollitt, Alice Y.; Fenton-May, Angharad E.; Johnson, Louise A.; Jackson, David G.; Watson, Steve P.; O'Callaghan, Chris A.

    2009-01-01

    We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and that it mediates powerful platelet aggregation by the snake venom toxin, rhodocytin. In addition, we have provided indirect evidence for an endogenous ligand for CLEC-2 in renal cells expressing human immunodeficiency virus type 1 (HIV-1). This putative ligand facilitates transmission of HIV through its incorporation into the viral envelope and binding to CLEC-2 on platelets. The aim of this study was to identify the ligand on these cells which binds to CLEC-2 on platelets. Recombinant CLEC-2 exhibits specific binding to 293T cells in which the HIV can be grown. Further, 293T cells activate both platelets and CLEC-2-transfected DT-40 B cells. The transmembrane protein podoplanin was identified on 293T cells and demonstrated to mediate both binding of 293T cells to CLEC-2 and 293T cell activation of CLEC-2-transfected DT-40 B cells. Podoplanin is expressed on renal cells (podocytes). Further, a direct interaction between CLEC-2 and podoplanin was confirmed using surface plasmon resonance and was shown to be independent of glycosylation of CLEC-2. The interaction has an affinity of 24.5 ± 3.7μM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells. PMID:18215137

  7. The angiographic incidence of renal artery stenosis in the arterioscleritic population

    International Nuclear Information System (INIS)

    Wils, G.; Marchal, G.; Peene, P.; Baert, A.L.

    1990-01-01

    The incidence of renal artery stenosis was evaluated with intra-arterial digital subtraction anghiography in 100 consecutive patients referred for peripheral arteriopathy. Fifty-seven patients were normotensive, 43 were hypertensive. In the normotensive group, renal artery stenosis was found in ten patients (17.5%). In the hypertensive group renal artery stenosis was found in twelve patients (28%). It is concluded that the incidence of renal aretery stenosis is high in an arterioslcerotic population both in normotensive and hypertensive patients. (author). 16 refs.; 1 tab

  8. Metastatic Renal Cell Carcinoma to Jejunum: An Unusual Case Presentation

    Directory of Open Access Journals (Sweden)

    Igor Medic

    2017-07-01

    Full Text Available The small intestine is a very uncommon and peculiar site for metastasis from renal cell carcinoma (RCC. We present a clinical presentation of insidious and unusual development of a jejunal metastasis while having stable disease in a remainder of metastatic sites, in a patient undergoing immunotherapy with nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this pathologic entity, particularly when the remainder of metastatic disease responds well to ongoing therapy.

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

    DEFF Research Database (Denmark)

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

    Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made...... Medical® was used. Treatment was considered successful when tumors gradually shrunk and showed no sign of contrast enhancement, assessed by CT or MRI. Results: Mean patient age and tumor size was 65 yr [17 - 83] and 26 mm [10 - 62], respectively [min-max]. Treatment modalities consisted of percutaneous...

  10. Evaluation of resectability of renal cell carcinoma by computed tomography

    International Nuclear Information System (INIS)

    Hiramatsu, Yoshihiro; Matsumoto, Kunihiko; Tatezawa, Takashi; Kikuchi, Yoichi; Akisada, Masahiro; Kitagawa, Ryuichi

    1982-01-01

    Renal cell carcinoma is one of the unique neoplasm which is characterized by disappearing of the metastatic tumors after removal of the primary lesion. Angiography has been performed to evaluate the resectability of the primary tumor by nephrectomy in the past. With the use of computed tomography, detailed evaluation of the retroperitoneal structures is now possible. We have evaluated the resectability of renal cell tumor by computed tomography and compared the results with the angiographic findings and operative findings. Computed tomography is very accurate in determining the extent of the tumor especially in evaluation of tumor and the Gerota's fascia, which is essential to determine the resectability of the tumor. Informations about lymph node metastasis and invasion to the renal veins or inferior vena cava are also obtained.FIn most of the cases, angiography can be spared if computed tomography is properly performed. (author)

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology......% intermediate risk, and 40% vs. 24% poor risk; P system metastases (6...... of second- (P = .018) and third-line (P systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P

  13. Validation of insulin resistance indexes in a stable renal transplant population

    NARCIS (Netherlands)

    Oterdoom, Leendert H.; de Vries, Aiko P. J.; van Son, Willem J.; Homan van der Heide, Jaap J.; Ploeg, Rutger J.; Gansevoort, Ron T.; de Jong, Paul E.; Gans, Rijk O. B.; Bakker, Stephan J. L.

    2005-01-01

    The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and

  14. Validation of insulin resistance indexes in a stable renal transplant population

    NARCIS (Netherlands)

    Oterdoom, LH; De Vries, APJ; Van Son, WJ; Van Der Heide, JJH; Ploeg, RJ; Gansevoort, RT; De Jong, PE; Gans, ROB; Bakker, SJL

    2005-01-01

    OBJECTIVE - The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. RESEARCH DESIGN AND METHODS - Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin

  15. Evaluation of morphologically unclassified renal cell carcinoma with electron microscopy and novel renal markers: implications for tumor reclassification.

    Science.gov (United States)

    Talento, Romualdo; Hewan-Lowe, Karlene; Yin, Ming

    2013-02-01

    Despite progress in the classification of renal cell carcinomas (RCC), a subset of these carcinomas remains unclassified (RCC-U). Patients with RCC-U usually present at a late stage and have a poor prognosis. Several studies have attempted to extract new classifications of newly recognized renal carcinomas from the group of RCC-U. However, to date, no studies in the literature have attempted to characterize the RCC-U with unrecognizable cell types beyond the morphologic evaluation on H&E-stained sections. The purpose of this study was to evaluate this group of RCC-U using electron microscopy and novel renal markers. Ten cases of such RCC-U were identified for this study. At the ultrastructural level, they did not show typical morphology that resembled any of the well-studied, recognizable subtypes of RCC. However, they did reveal features of renal tubular epithelial differentiation. The histologic, ultrastructural, and immunophenotypic features indicated that these tumors are poorly differentiated renal epithelial tumors, possibly derived from the proximal nephron, with an immunohistochemical profile similar to high-grade clear cell RCC. It is, therefore, proposed that this group of renal carcinomas be renamed "poorly differentiated renal cell carcinoma, not otherwise specified." The current study showed that PAX-8 and carbonic anhydrase IX are reliable markers for this novel group of renal carcinoma, and that electron microscopy is an important adjunct in the evaluation of new and unusual renal entities.

  16. The relationship of mast cells and angiogenesis with prognosis in renal cell carcinoma

    International Nuclear Information System (INIS)

    Guldur, M.E.; Kocarslan, S.; Dincoglu, D.

    2014-01-01

    Objective: To evaluate the effects of mast cell count and angiogenesis on the prognosis of renal cell carcinoma. Methods: The retrospective study was conducted at the Harran University, Sanliurfa, Turkey, and included 64 cases with diagnosis of renal cell carcinoma between 2002 and 2012. Immunohistochemical analysis was performed on paraffin sections using the standard streptavidin-biotin immunoperoxidase method. CD31 antibodies were used to identify microvessels in tumoural tissues. The microvessel density was calculated using a serological method. The mean vascular density was equivalent to the vascular surface area (in mm) per unit tissue volume (in mm) (MVD=mm). Mast cells tryptase antibody was used to evaluate the mast cell count in tumoural and non-tumoural tissues. The relationship between mast cell count and microvessel density was evaluated and compared with stage, grade, tumour diameter, and age. Results: The mast cell count in the tumoral tissue of renal cell carcinoma was significantly higher compared with non-neoplastic renal tissue (p 0.05). The intratumoural mast cell count in clear cell renal carcinoma was significantly higher compared with non-clear variety (p=0.001). No significant relationship was found between microvessel density, age, stage, diameter, or grade of the tumour and tumoral mast cell count (p>0.05). Conclusion: No significant association was found between the number of mast cells in tumoral tissue and microvessel density. Further studies are needed to demonstrate the effect of mast cells on angiogenesis in renal cell carcinoma. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-15

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

  19. Understanding familial and non-familial renal cell cancer

    NARCIS (Netherlands)

    Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J. M.; Eleveld, Marc J.; Martens, Gerard J. M.; Weterman, Marian A. J.; van Kessel, Ad Geurts

    2002-01-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

  20. Understanding familial and non-familial renal cell cancer.

    NARCIS (Netherlands)

    Bodmer, D.; Hurk, W.H. van den; Groningen, J.J.M. van; Eleveld, M.J.; Martens, G.J.M.; Weterman, M.A.J.; Geurts van Kessel, A.H.M.

    2002-01-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

  1. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Todenhöfer Tilman

    2012-03-01

    Full Text Available Abstract Background Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma. Case presentation A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable. Conclusions Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.

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

    Directory of Open Access Journals (Sweden)

    Shouki Bazarbashi

    2011-01-01

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

  3. A Stauffer's syndrome variant associated with renal cell carcinoma ...

    African Journals Online (AJOL)

    İ. Ateş

    2015-10-09

    Oct 9, 2015 ... Stauffer's syndrome is a rare paraneoplastic manifestation of renal cell carcinoma which is characterized by elevated alkaline ... In this case report, we report a patient who was admitted with fever, fatigue, abdominal pain, weight loss and ... have a history of chronic disease, smoking, alcohol or drug use.

  4. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to an...

  5. A brief symptom index for advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cella David

    2006-09-01

    Full Text Available Abstract Background Our objective was to test a brief, symptom index for advanced renal cell carcinoma, a disease affecting over 38,000 Americans each year and often diagnosed in late stages. Methods We conducted secondary data analyses on patient-reported outcomes of 209 metastatic renal cell carcinoma patients participating in a Phase III clinical trial. Patient-reported outcomes, obtained from the FACT-Biological Response Modifier (FACT-BRM scale, were available at baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously identified by clinical experts to represent the most important symptoms of advanced renal cell carcinoma. Items comprising this index assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher scores indicating fewer symptoms. We determined reliability and validity of the index and estimated a minimally important difference. Results The index had excellent internal reliability at all three time points (alphas ≥ 0.83. Baseline scores were able to discriminate patients across Karnofsky performance status, number of metastatic sites, and risk group categories (ps Conclusion The 8-item index of patient-reported symptoms of renal cell carcinoma appears to be a psychometrically sound measure. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies.

  6. The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

    NARCIS (Netherlands)

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

    2014-01-01

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

  7. Renal cell carcinoma in children and adolescence: Our experience ...

    African Journals Online (AJOL)

    Background: Literature on renal cell carcinoma (RCC) in children is lacking. Occasional case report has been mentioned. Aims and objective of our study are to evaluate the clinical presentation and outcome in children with RCC. Patients and Methods: Records of 11 children and adolescence, from January 2007 to June ...

  8. Renal cell carcinoma: an atypical case containing fat

    International Nuclear Information System (INIS)

    Saez Castan, J.; Perez Paya, F.; Ramon Sanchez, J.; Rausell Felix, M.; Alpera Tenza, M.; Orti Tarazona, C.

    1995-01-01

    An atypical form of presentation of renal cell carcinoma is reported. The lesion contained fat collections, an exceptional findings in these neoplasms. We describe the intravenous urography, ultrasound and CT images, as well as the preoperative follow-up using CT, performed 11 months after the first study. 11 refs

  9. UK Renal Registry 11th Annual Report (December 2008): Chapter 13 Demography of the UK paediatric renal replacement therapy population.

    Science.gov (United States)

    Lewis, Malcolm A; Shaw, Joanne; Sinha, Manish; Adalat, Shazia; Hussain, Farida; Inward, Carol

    2009-01-01

    To describe the demographics of the paediatric RRT population in the UK and analyse changes in demographics with time. Extraction and analysis of data from the UK paediatric Renal Registry. The UK paediatric established renal failure (ERF) population in April 2008 was 875 patients. The prevalence under the age of 16 years was 55 per million age related population (pmp) and the incidence 7.92 pmp. The incidence and prevalence for South Asian and Other ethnic groups were 3 times that of the White and Black populations. Renal dysplasia was the most common cause of ERF accounting for 33% of prevalent cases. Diseases with autosomal recessive inheritance were more common in patients from ethnic minority groups. The spectrum of diseases seen has changed over a generation. Overall 5 year survival for children with ERF was 91.8%. Five year survival of infants starting dialysis was just 62%. Transplanted patients accounted for 74% of the current population. The proportion with grafts from living donors has steadily risen to 34%. Children from ethnic minority groups were less likely to have an allograft and living donation was less frequent in this population. For those on dialysis, 57% were receiving peritoneal dialysis. This was the main treatment modality for patients under 4 years of age. The paediatric ERF population continued to expand slowly. Incidence and prevalence rates were stable and similar to other developed nations. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population. The spectrum of diseases seen has already changed over a generation with the treatment of young children with diseases such as congenital nephrosis. The incidence of cystinosis causing ERF was reduced, probably reflecting better early treatment. Copyright 2009 S. Karger

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

    Directory of Open Access Journals (Sweden)

    Rossi Michele

    2003-02-01

    Full Text Available Abstract 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.

  11. Tubulocystic renal cell carcinoma: a new radiological entity

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

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

    Directory of Open Access Journals (Sweden)

    Turker Acar

    2014-01-01

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

  13. Renal sinus fat invasion and tumoral thrombosis of the inferior vena cava-renal vein: only confined to renal cell carcinoma.

    Science.gov (United States)

    Acar, Turker; Harman, Mustafa; Guneyli, Serkan; Sen, Sait; Elmas, Nevra

    2014-01-01

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

  14. Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

    Science.gov (United States)

    Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

    2017-02-01

    Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

  15. Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

    Science.gov (United States)

    Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

    2017-11-01

    To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Chiara Paglino

    2011-12-01

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

  17. Third-line Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

    Science.gov (United States)

    Wells, J Connor; Stukalin, Igor; Norton, Craig; Srinivas, Sandy; Lee, Jae Lyun; Donskov, Frede; Bjarnason, Georg A; Yamamoto, Haru; Beuselinck, Benoit; Rini, Brian I; Knox, Jennifer J; Agarwal, Neeraj; Ernst, D Scott; Pal, Sumanta K; Wood, Lori A; Bamias, Aristotelis; Alva, Ajjai S; Kanesvaran, Ravindran; Choueiri, Toni K; Heng, Daniel Y C

    2017-02-01

    The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population. To evaluate the use and efficacy of targeted therapy in a third-line setting. Twenty-five international cancer centers provided consecutive data on 4824 mRCC patients who were treated with an approved targeted therapy. One thousand and twelve patients (21%) received TTT and were included in the analysis. Patients were analyzed for overall survival (OS) and progression-free survival using Kaplan-Meier curves, and were evaluated for overall response. Cox regression analyses were used to determine the statistical association between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status. Everolimus was the most prevalent third-line therapy (27.5%), but sunitinib, sorafenib, pazopanib, temsirolimus, and axitinib were all utilized in over ≥9% of patients. Patients receiving any TTT had an OS of 12.4 mo, a progression-free survival of 3.9 mo, and 61.1% of patients experienced an overall response of stable disease or better. Patients not receiving TTT had an OS of 2.1 mo. Patients with favorable- (7.2%) or intermediate-risk (65.3%) disease had the highest OS with TTT, 29.9 mo and 15.5 mo, respectively, while poor-risk (27.5%) patients survived 5.5 mo. Results are limited by the retrospective nature of the study. TTT remains highly heterogeneous. The IMDC prognostic criteria can be used to stratify third-line patients. TTT use in favorable- and intermediate-risk patients was associated with the greatest OS. Patients with favorable- and intermediate-prognostic criteria disease treated with third-line targeted therapy have an associated

  18. mTOR inhibitors in the treatment of advanced renal cell carcinoma

    International Nuclear Information System (INIS)

    Barilla, R.; Sycova-Mila, Z.

    2009-01-01

    Renal Cell Carcinoma (RCC) accounts for approximately 4 % of all malignancies. Much is known about the pathogenesis of RCC because of studies examining its close relationship with dysfunction of the Von Hippel-Lindau gene (VHL) and hypoxia inducible factor (HIF). Mammalian target of rapamycin (mTOR) regulates nutritional needs, cell growth, and angiogenesisi in cells by down regulating or up regulating a variety of proteins including HIF. Until 2005, only a single agent high dose interleukin 2 was approved by Food and Drug Administration (FDA) for treatment of advanced renal cell carcinoma. More recently thanks to better knowledge in the field of molecular biology new treatment options appeared. Sunitinib and bevacizumab are currently considered to be treatment of first choice for patients in good and intermediate prognostic group and sorafenib is preferred second line treatment in the same patient population pretreated with cytokines after disease progression. Temsirolimus and everolimus, rapamycin analouges, have recently been tested in III trials in first and second line treatment in patients with advanced metastatic clear cell renal cell carcinoma. (author)

  19. Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

    Science.gov (United States)

    Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

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

    Directory of Open Access Journals (Sweden)

    Chen C

    2003-01-01

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

  1. Computed tomographic demonstration of a spontaneous subcapsular hematoma due to a small renal cell carcinoma

    International Nuclear Information System (INIS)

    Hilton, S.; Bosniak, M.A.; Megibow, A.J.; Ambos, M.A.

    1981-01-01

    Computed tomography (CT) was able to demonstrate a small renal cell carcinoma as the cause of a spontaneous subcapsular hematoma. Angiographic and pathologic correlation were obtained. A review of the causes for nontraumatic renal subcapsular hematoma is included

  2. Stem cells and their role in renal ischaemia reperfusion injury.

    Science.gov (United States)

    Bagul, Atul; Frost, Jodie H; Drage, Martin

    2013-01-01

    Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC. Copyright © 2012 S. Karger AG, Basel.

  3. Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and renal cell carcinoma cancer stem cells research model.

    Science.gov (United States)

    Krawczyk, Krzysztof M; Matak, Damian; Szymanski, Lukasz; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M

    2018-04-01

    The use of fetal bovine serum hinders obtaining reproducible experimental results and should also be removed in hormone and growth factor studies. In particular hormones found in FBS act globally on cancer cell physiology and influence transcriptome and metabolome. The aim of our study was to develop a renal carcinoma serum free culture model optimized for (embryonal) renal cells in order to select the best study model for downstream auto-, para- or endocrine research. Secondary aim was to verify renal carcinoma stem cell culture for this application. In the study, we have cultured renal cell carcinoma primary tumour cell line (786-0) as well as human kidney cancer stem cells in standard 2D monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco's Modified Eagle's Medium and Complete Human Kidney Cancer Stem Cell Medium, respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media were tested. Our results revealed that xeno-free embryonal renal cells optimized culture media provide a useful tool in RCC cancer biology research and at the same time enable effective growth of RCC. We propose bio-mimic RCC cell culture model with specific serum-free and xeno-free medium that promote RCC cell viability.

  4. THE EPIGENETICS OF RENAL CELL TUMORS: FROM BIOLOGY TO BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Rui eHenrique

    2012-05-01

    Full Text Available Renal cell tumors (RCT collectively constitute the third most common type of genitourinary neoplasms, only surpassed by prostate and bladder cancer. They comprise a heterogeneous group of neoplasms with distinctive clinical, morphological and genetic features. Epigenetic alterations are a hallmark of cancer cells and their role in renal tumorigenesis is starting to emerge. Aberrant DNA methylation, altered chromatin remodeling / histone onco-modifications and deregulated microRNA expression not only contribute to the emergence and progression of RCTs, but owing to their ubiquity, they also constitute a promising class of biomarkers tailored for disease detection, diagnosis, assessment of prognosis and prediction of response to therapy. Moreover, due to their dynamic and reversible properties, those alterations represent a target for epigenetic-directed therapies. In this review, the current knowledge about epigenetic mechanisms and their altered status in RCT is summarized and their envisaged use in a clinical setting is also provided.

  5. A Unique Presentation of an Undiagnosed Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Georgios Kravvas

    2014-01-01

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

  6. Asymptomatic dedifferentiated liposarcoma mimicking renal cell ...

    African Journals Online (AJOL)

    M. El Howairis

    2016-11-23

    Nov 23, 2016 ... Production and hosting by Elsevier B.V. This is an open ... bilateral cataracts which had been previously treated successfully. ... multidisciplinary approach is paramount to treat the patient effec- tively ... Portsite recurrence after laparoscopy for stag- ... population-based analysis of epidemiology, surgery, and ...

  7. Evaluation of extent of UTI related renal parenchymal damage in pediatric patient population

    International Nuclear Information System (INIS)

    Sharma, A.R.; Charan, S.; Silva, I.

    2004-01-01

    Introduction: Urinary tract infection (UTI) is important cause of morbidity in childhood. UTI may lead to involvement of renal parenchyma ranging from recoverable acute inflammation, renal scarring of Reflux nephropathy, hypertension and ultimately end stage renal disease. Hence, extent of renal parenchymal involvement bears prognostic significance in pediatric population. Laboratory and clinical parameters have inherent limitations in detecting and localizing renal parenchymal involvement in the settings of UTI. Objectives: The present study has been designed with the aim to determine the frequency and degree of renal parenchymal involvement in pediatric patients having urinary tract infection. MATERIALS AND METHODS: From May to December 2003, 33 consecutive children (65 Kidneys, 32-paired, I-solitary) aged one month to 12 years (mean age 3 years, 20M, 13F) with positive past history and culture documented urinary tract infection were enrolled in the study. They were subjected to Renal cortical scan using Tc-99m DMSA (20-100 MBq) on Dual detectors gamma camera (e.cam) fitted with LEHR collimator in anterior, posterior and posterior oblique projections. DMSA renal scans were interpreted as per Clarke's interpretation criteria. Renal ultrasound (RUS) and cystourethrogram (MCUG) were available in all the cases. Results: As per Clarke's classification, there were 19 children with no evidence of renal cortical involvement (Type-1). Renal parenchymal involvement found to be unilateral (Type-4 to Type-6) and bilateral (Type-7 and 8) in 8 and 6 children respectively. DMSA scan was abnormal in 20 of 65 kidneys (31%). MCUG was positive for presence of VUR in 34 kidneys (Group A) and negative for VUR in remaining 31 units (Group B). In Gp A, 18 of 34 kidneys (53%) showed renal parenchymal involvement on DMSA Scan. In Gp A, presence or absence of renal parenchymal damage on DMSA scan did not show any statistically significant difference in age, sex and grade of VUR. Whereas

  8. Colonic metastasis from renal cell carcinoma: helical-CT demonstration

    International Nuclear Information System (INIS)

    Diaz-Candamio, M.J.; Pombo, S.; Pombo, F.

    2000-01-01

    Clinically evident colonic metastasis from renal cell carcinoma (RCC) is rare. In the present study a hypervascular sigmoid mass was demonstrated on arterial-phase helical CT using a water enema in a patient who had suffered left nephrectomy 8 years previously for RCC. The intense and early enhancement of the lesion suggested the possibility of a solitary colonic metastasis from RCC, a diagnosis which was pathologically confirmed. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

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

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

    OpenAIRE

    B. T. Dzumabaeva; L. S. Birjukova; L. B. Kaplanskaya; D. P. Maksimov

    2011-01-01

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

  11. Computed tomography findings of pancreatic metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    Prando, Adilson

    2008-01-01

    Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

  12. Chronological alterations of diagnostic imaging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Arima, Kiminobu; Sugimura, Yoshiki; Yanagawa, Makoto; Tochigi, Hiromi; Kawamura, Juichi

    1994-01-01

    A review of 156 cases of renal cell carcinoma diagnosed during a 20-year period demonstrated the changes of initial signs/symptoms and imaging modalities for detection and definition. According to the imaging modality used for diagnosing renal cell carcinoma, clinical pictures were chronologically examined over 4 periods: 1973 to 1979 (before CT era), 1980 to 1984 (early CT era), 1985 to 1987 (CT era) and 1988 to 1992 (CT/MRI era). With regards to initial signs or symptoms, the proportion of classical trials has gradually decreased, while that of tumors noted incidentally has increased. As for imaging modalities for detection, the proportion of IVP has gradually decreased and that of CT and US has increased over the periods. With regard to imaging modalities for definition, the proportion of angiography has decreased and that of CT has increased. From chronological changes in clinical pictures and imaging modalities, we suggested a decision tree of imaging modalities for detection and definition of renal cell carcinoma. (author)

  13. Computed tomography findings of pancreatic metastases from renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Prando, Adilson [Hospital Vera Cruz, Campinas, SP (Brazil). Dept. of Radiology and Imaging Diagnosis]. E-mail: adilson.prando@gmail.com

    2008-07-15

    Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

  14. Squamous cell carcinoma of tongue 18 years after renal transplantation:a case report

    Institute of Scientific and Technical Information of China (English)

    Jyoti Poddar; Ashutosh Das Sharma

    2016-01-01

    Solid organ transplant recipients are at increased risk of developing malignancies, even decades after transplant, due to the prolonged use of immunosuppressant drugs. A 35-year-old male underwent renal transplant for end stage renal disease 18 years previously and was on immunosuppressive drugs since that time and was on regular follow up. In 2016, he developed a squamous cell carcinoma of tongue, which was operated and adjuvant radiation therapy was given. The patient is currently on follow up and asymptomatic. Though squamous cell carcinoma of tongue is a relatively common malignancy in the general population, it is very rare in transplant recipients. Hence, such patients require longer follow-up, active surveillance, and screening for early diagnosis and prompt treatment of premalignant and malignant conditions.

  15. Chapter 22. Cell population kinetics

    International Nuclear Information System (INIS)

    Tubiana, M.

    1975-01-01

    The main contribution of radioisotopes to the development of a new discipline, cell population kinetics, was shown. The aim of this science is to establish, for each tissue of the organism, the life span of its component cells and the mechanisms governing its growth, its differentiation and its homeostasis with respect to outside attacks. Labelling techniques have been used to follow the cells during these various processes. The case of non-dividing cells was considered first, taking as example, the red blood cells of which the lifetime was studied, after which the case of proliferating cells was examined using 14 C- or tritium-labelled thymidine. The methods used to measure the cell cycle parameters were described: labelled-mitosis curve method, double-labelling and continuous labelling methods, proliferation coefficient measurement. Cell kinetics were shown to allow an interpretation of radiobiological data. Finally the practical value of cell kinetics research was shown [fr

  16. [Case report of rare co-occurrence of renal cell carcinoma and crossed renal dystopia (L-shaped kidney)].

    Science.gov (United States)

    Bakov, V N; Los, M S

    2017-10-01

    L-shaped kidney refers to a rare anomaly of the relative kidney positioning. Due to low prevalence, the literature on the co-occurrence of this anomaly with malignancy is lacking. And, if the diagnosis of a renal anomaly does not present difficulties, if a tumor is detected in such a kidney, even MSCT does not always help differentiate a pelvic tumor from a tumor of the renal parenchyma spreading to the pelvicalyceal system. This has important implications for choosing an appropriate surgical strategy. A feature of the presented clinical observation is the co-occurrence of the rare anomaly of kidney position and locally advanced renal cell carcinoma spreading to the renal pelvis. Due to the massive spread of the tumor, an organ-sparing surgery was not feasible. Due to the suspicion of tumor spread to the renal pelvis, the patient underwent nephrureterectomy of the L-shaped kidney. Introduction to renoprival state with transfer to chronic hemodialysis became the only option to maintain homeostasis and extend the patients life. Histological examination revealed clear cell renal cell carcinoma with invasion of the pelvis and renal capsule, with no clear demarcation between the fused kidneys.

  17. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

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

  18. Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

    OpenAIRE

    Hayam Abdel Meguid El Aggan; Mona Abdel Kader Salem; Nahla Mohamed Gamal Farahat; Ahmad Fathy El-Koraie; Ghaly Abd Al-Rahim Mohammed Kotb

    2013-01-01

    Introduction: Chronic allograft nephropathy (CAN) is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs) and mesenchymal stem cells (MSCs). Char...

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

    Directory of Open Access Journals (Sweden)

    Juan Manuel Senior Sánchez

    2006-01-01

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

  20. Does injection of metanephric mesenchymal cells improve renal function in rats?

    Directory of Open Access Journals (Sweden)

    Yu-qing Jiao

    2011-01-01

    Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

  1. Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

    Science.gov (United States)

    Smeets, Bart; Angelotti, Maria Lucia; Rizzo, Paola; Dijkman, Henry; Lazzeri, Elena; Mooren, Fieke; Ballerini, Lara; Parente, Eliana; Sagrinati, Costanza; Mazzinghi, Benedetta; Ronconi, Elisa; Becherucci, Francesca; Benigni, Ariela; Steenbergen, Eric; Lasagni, Laura; Remuzzi, Giuseppe; Wetzels, Jack; Romagnani, Paola

    2009-12-01

    Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

  2. Renal intercalated cells and blood pressure regulation

    Directory of Open Access Journals (Sweden)

    Susan M. Wall

    2017-12-01

    Full Text Available Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

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

    Directory of Open Access Journals (Sweden)

    İbrahim İlker Öz

    2014-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Nevins

    2013-01-01

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

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

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-11-15

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

  8. Renal transitional cell carcinoma: a sonographic and radiological correlation

    International Nuclear Information System (INIS)

    Prando, A.; Marins, J.L.C.; Prando, D.; Pereira, R.M.

    1984-01-01

    A sonographic study was performed on nine patients with renal transitional cell carcinoma and the findings correlated with those of excretory urography, retrograde and/or antegrade pyelography. In six patients the correct diagnosis was considered mainly by the radiological features. In the remaining three patients, due to its unusual manifestations, this diagnosis was accomplished only by sonography. A small echogenic mass at the peryphery of a chronic hydronephrotic kidney, a huge complex mass due to a multiple arborescent papilary tumor and a demonstration of a mass in a presumptive renal pelvic inflammatory disease, respectively, represented these uncommon aspects. The spectrum of features of this entity and the related differential diagnosis are also presented. (Author) [pt

  9. Serum chemerin levels are inversely associated with renal function in a general population

    DEFF Research Database (Denmark)

    Zylla, Stephanie; Rettig, Rainer; Völzke, Henry

    2018-01-01

    OBJECTIVE: Chemerin has been found to be highly expressed in the kidneys of rodents and has been suggested to affect metabolic syndrome (MetS)-related phenotypes which are in turn related to kidney damage. Only few clinical studies have addressed the relation between circulating chemerin and renal...... function in humans, and no population-based analyses have yet been performed. The potential influence of MetS-related phenotypes on the assumed association has been largely neglected. We aimed to investigate the association of serum chemerin with renal function in a general population with special regard......GFR and revealed that each increase in chemerin per 25 ng/mL was associated with an about threefold higher odds of chronic kidney disease [odds ratio 2.72 (95% confidence interval 2.26-3.29)]. CONCLUSIONS: Our results demonstrate a strong inverse association between serum chemerin levels and renal function...

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

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

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

  11. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

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    Fengju Chen

    2016-03-01

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

  12. Racial difference in histologic subtype of renal cell carcinoma

    International Nuclear Information System (INIS)

    Olshan, Andrew F; Kuo, Tzy-Mey; Meyer, Anne-Marie; Nielsen, Matthew E; Purdue, Mark P; Rathmell, W Kimryn

    2013-01-01

    In the United States, renal cell carcinoma (RCC) has rapidly increased in incidence for over two decades. The most common histologic subtypes of RCC, clear cell, papillary, and chromophobe have distinct genetic and clinical characteristics; however, epidemiologic features of these subtypes have not been well characterized, particularly regarding any associations between race, disease subtypes, and recent incidence trends. Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we examined differences in the age-adjusted incidence rates and trends of RCC subtypes, including analysis focusing on racial differences. Incidence rates increased over time (2001–2009) for all three subtypes. However, the proportion of white cases with clear cell histology was higher than among blacks (50% vs. 31%, respectively), whereas black cases were more likely than white cases to have papillary RCC (23% vs. 9%, respectively). Moreover, papillary RCC incidence increased more rapidly for blacks than whites (P < 0.01) over this period. We also observed that increased incidence of papillary histology among blacks is not limited to the smallest size strata. We observed racial differences in proportionate incidence of RCC subtypes, which appear to be increasing over time; this novel finding motivates further etiologic, clinical, molecular, and genetic studies. Using national data, we observed a higher proportion of black renal cell carcinoma (RCC) cases with papillary histology compared to Caucasian cases. We also observed time trends in black-white incidence differences in histologic RCC subtypes, with rapid increases in the disproportionate share of black cases with papillary histology

  13. βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.

    Science.gov (United States)

    Drummond, Heather A; Stec, David E

    2015-06-01

    Pressure-induced constriction (also known as the "myogenic response") is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na + Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

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

    Directory of Open Access Journals (Sweden)

    Sadhukhan Provash

    2004-06-01

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

  15. Need for a nomogram of renal sizes in the Indian population- findings from a single centre sonographic study

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    Prakash Muthusami

    2014-01-01

    Full Text Available Background & objectives: Renal size is an important parameter used in the diagnosis and follow up of renal diseases. However, while making decisions, clinicians must be aware of the dependence of these dimensions on the ethnicity of the individual, independent of anthropometric indices. There is no established nomogram for renal sizes in the Indian population. The aim of this study was to assess the applicability of oft-quoted ranges of normal renal sizes in our population. Methods: Renal dimensions including length, width and parenchymal thickness were sonographically measured in 140 individuals with no renal disease. Analysis was done for differences due to age, gender and laterality. The correlation of renal dimensions with anthropometric parameters like weight, height, body mass index (BMI and body surface area (BSA was analyzed. Results: The means of length, width and parenchymal thickness of all 280 kidneys of 140 patients were 9.65 ± 0.63, 4.5 ± 0.42 and 2.04 ± 0.2 cm, respectively. There was a significant difference in parenchymal thickness between the right and left kidneys, while there was no significant right-left difference in length or width. Gender-wise analysis showed significant differences between male and female renal breadths but not length and parenchymal thickness. Age group-wise analysis showed significant decrease in renal length and parenchymal thickness beyond the seventh decade. There was a moderate positive correlation of bilateral renal length with body weight and BSA, and a weak positive correlation with body height and BMI. Interpretation & conclusions: Renal sizes in our population are in contrast to commonly quoted normal values in literature. Conclusions about renal sizes need to be made with reference to nomograms and should not be based upon data from other populations. We also present formulae whereby to derive renal sizes from anthropometric indices in our population.

  16. Prevalence of renal artery stenosis in subjects with moderate hypertension. A population-based study

    DEFF Research Database (Denmark)

    Andersen, Ulrik B; Borglykke, Anders; Jørgensen, Torben

    2011-01-01

    Abstract Aim. To examine the prevalence of significant renal artery stenosis (RAS) in subjects with moderate to severe hypertension. Materials and methods. Subjects aged 50-66 years with blood pressure >160/100 mmHg or receiving antihypertensive treatment were selected from the population study...

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Novel approach to recurrent cavoatrial renal cell carcinoma.

    Science.gov (United States)

    Alejo, Jennifer L; George, Timothy J; Beaty, Claude A; Allaf, Mohamad E; Black, James H; Shah, Ashish S

    2012-05-01

    Renal cell carcinoma (RCC) with cavoatrial extension is a rare and complex problem. Complete resection is difficult but correlates with favorable patient outcomes. We present 2 cases of successful reoperative resections of recurrent RCC in patients with level III-IV cavoatrial involvement. We used a thoracoabdominal approach, peripheral cannulation, and hypothermic circulatory arrest. We advocate this novel approach as a successful means of avoiding a more difficult reoperation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. The Role of Everolimus in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Malek Meskawi

    2015-12-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2010-04-22

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

  1. Experience with renal cell carcinoma-a single centre study from Khyber Pakhtunkhwa

    International Nuclear Information System (INIS)

    Khan, H. S.; Mahmood, A.

    2017-01-01

    Objective: To analyze the clinical characteristics, management and outcome of renal cell carcinoma (RCC) and its variants in patients treated at CMH Peshawar, from Aug 2011 to Aug 2014. Study Design: Retrospective descriptive. Place and Duration of Study: Combined Military Hospital (CMH) Peshawar, from Aug 2011 to Aug 2014. Material and Methods: All patients who underwent nephrectomy for renal masses at our institution between Aug 2011 and Aug 2014 were included in the study. The demographic distribution, symptoms, tumour characteristics, operative findings and histopathology reports were extracted from the hospital records and analysed via SPSS version 20.0. Results: Among 27 patients male to female ratio was 1.25:1. Mean age was 55.5 ± 11.7 years. Flank pain was the commonest symptom reported. Mean maximum diameter of the tumour was 13.6 ± 4.6 cm. All the tumours were malignant and most common histopathological type was conventional/clear cell RCC. All patients were treated by radical nephrectomy through transperitoneal approach. One patient developed post operative thrombosis of inferior vena cava. Two patients developed metastatic deposit during follow up. Conclusion: Renal tumours in the study population of Khyber Pakhtunkhwa at our centre presented late with large sizes, and incidental diagnosis is rare. Health education and availability of advanced diagnostic facilities will improve outcomes. (author)

  2. Renal cell carcinoma: incidental detection and pathological staging.

    Science.gov (United States)

    Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

    2000-10-01

    In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Hemodynamic and glucometabolic factors fail to predict renal function in a random population sample

    DEFF Research Database (Denmark)

    Pareek, M.; Nielsen, M.; Olesen, Thomas Bastholm

    2015-01-01

    indices of beta-cell function (HOMA-2B), insulin sensitivity (HOMA-2S), and insulin resistance (HOMA-2IR)), traditional cardiovascular risk factors (age, sex, smoking status, body mass index, diabetes mellitus, total serum cholesterol), and later renal function determined as serum cystatin C in 238 men...

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

    Directory of Open Access Journals (Sweden)

    Min Su Cheong

    2010-07-01

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

  6. Increased risk of dialysis and end-stage renal disease among HIV patients in Denmark compared with the background population

    DEFF Research Database (Denmark)

    Rasch, Magnus G; Helleberg, Marie; Feldt-Rasmussen, Bo

    2014-01-01

    BACKGROUND: HIV patients have increased risk of impaired renal function. We aimed to estimate the incidence of any renal replacement therapy (aRRT) and start of chronic renal replacement therapy (cRRT) among HIV patients compared with population controls. METHODS: In a nationwide, population......-based cohort study we analysed incidence rates (IR), incidence rate ratios (IRR) and risk factors for aRRT and cRRT among HIV patients compared with an age- and gender-matched population control cohort using Poisson regression. RESULTS: We identified 5300 HIV patients and 53 000 population controls. The IRs...

  7. The role of glutathione transferases in renal cell carcinoma

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    Ćorić Vesna

    2016-01-01

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

  8. Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

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    Marcos F. Dall'Oglio

    2005-02-01

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

  9. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection.

    Science.gov (United States)

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-11-03

    Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules including chemokine receptor type 5 (CXCR5), inducible T cell co-stimulator (ICOS), programmed death-1 (PD-1), ICOSL, PDL-1 and interleukin-21 (IL-21), of peripheral blood were comparatively measured in 42 primary renal allograft recipients within 1-3 years after transplantation. Among them, 24 patients had definite chronic rejection, while other 18 patients had normal renal function. Tfh-cell ratio was significantly increased with PD-1 down-regulation in the patients with chronic renal allograft rejection, while B cells and the alloimmune-regulating molecules studied did not show any appreciable change in parallel. The patients with chronic renal allograft rejection have a characteristic increase in circulating Tfh cells with a decrease in PD-1 expression. These pathological changes may be a therapeutic target for the treatment of chronic renal allograft rejection and can be useful as a clinical index for monitoring conditions of renal transplant.

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

    Science.gov (United States)

    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 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.

  11. Renal cell carcinoma with t(6,11: A case report and review of literature

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    K S Jansi Prema

    2017-01-01

    Full Text Available Renal cell carcinomas (RCCs with t(6,11 are very rare tumours. Only a few cases have been reported so far. t(6,11 results in fusion of alpha gene and transcription factor EB (TFEB gene resulting in the overexpression of TFEB. The specific light and immunohistochemical features help in the diagnosis of this rare type of tumor. We report a case of t(6,11 RCC in a 38-year-old female who was incidentally found to have a right renal mass. We present this case to emphasize the typical light microscopic picture of this extremely rare tumor. Two population of cells are seen: larger cells with abundant cytoplasm and smaller cells with scant cytoplasm. Smaller cells are arranged around hyaline nodules resulting in the formation of characteristic pseudorosettes. Immunohistochemically, these tumors are diffusely positive for vimentin and focally positive for HMB 45 and CD 117. Knowledge about the typical biphasic light microscopic appearance and the characteristic immunohistochemical features help in the diagnosis of this rare type of translocation associated RCC.

  12. Population dynamics in vasopressin cells.

    Science.gov (United States)

    Leng, Gareth; Brown, Colin; Sabatier, Nancy; Scott, Victoria

    2008-01-01

    Most neurons sense and code change, and when presented with a constant stimulus they adapt, so as to be able to detect a fresh change. However, for some things it is important to know their absolute level; to encode such information, neurons must sustain their response to an unchanging stimulus while remaining able to respond to a change in that stimulus. One system that encodes the absolute level of a stimulus is the vasopressin system, which generates a hormonal signal that is proportional to plasma osmolality. Vasopressin cells sense plasma osmolality and secrete appropriate levels of vasopressin from the neurohypophysis as needed to control water excretion; this requires sustained secretion under basal conditions and the ability to increase (or decrease) secretion should plasma osmolality change. Here we explore the mechanisms that enable vasopressin cells to fulfill this function, and consider how coordination between the cells might distribute the secretory load across the population of vasopressin cells. 2008 S. Karger AG, Basel.

  13. Comparative diagnostic study of staging in renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Masaharu; Mori, Masaki; Ito, Sachiko and others

    1986-04-01

    A comparative diagnostic study was carried out on 56 patients with pathologically proven renal cell carcinoma which had been staged by CT, US, angiography (AG) and lymphography (LG) between June, 1980, and May, 1985. The confirmation of the tumor extent was established by surgery and microscopic examination in all patients except three, in whom the extent of the tumor was determined at autopsy. CT and AG were performed in all cases. It was also studied how far various factors such as histologic architecture, cell type, grade, growth mode, tumor necrosis and bleeding were related with prognosis, and how to evaluate them in imaging modality. Concerning the T factor, there was no difference in diagnostic ability between images, and since prognosis of T4 was inferior to those of T2 and T3, diagnosis of T4 was seen to require particular attention. Drawing ability of N and V factors was poor in US. In LG, evaluation of regional lymph nodes was difficult, so this seems to be an unnecessary examination because CT can provide sufficient evaluation. By imaging modality, diagnosis of architecture and cell type was difficult. By AG, avascular to hypovascular tumors were of solid type, and there were many spindle or pleomorphic cell types and combination of tubular-granular types, while the papillary type was few. By macroscopic growth mode, the infiltrating type was poor in prognosis, and the presence or absence of halo was evaluated by CT and AG. Prognosis was favorable in cases having no necrosis in the tumor or accompanied by hemorrhage. For the purpose of diagnosis, CT was found to be sufficient, and it was concluded that AG may be used only for the purpose of renal arterial embolization as a preoperative treatment of low-stage cases subjected to nephrectomy. US is sufficient only if satisfying the role of screening. (J.P.N.).

  14. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection

    OpenAIRE

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-01-01

    Background Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. Methods The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules inc...

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  16. Electrolyte composition of renal tubular cells in gentamicin nephrotoxicity

    International Nuclear Information System (INIS)

    Matsuda, O.; Beck, F.X.; Doerge, A.T.; Thurau, K.

    1988-01-01

    The effect of long-term gentamicin administration on sodium, potassium, chloride and phosphorus concentrations was studied in individual rat renal tubular cells using electron microprobe analysis. Histological damage was apparent only in proximal tubular cells. The extent of damage was only mild after 7 days of gentamicin administration (60 mg/kg body wt/day) but much more pronounced after 10 days. GFR showed a progressive decline during gentamicin treatment. In non-necrotic proximal tubular cells, sodium was increased from 14.6 +/- 0.3 (mean +/- SEM) in controls to 20.6 +/- 0.4 after 7 and 22.0 +/- 0.8 mmol/kg wet wt after 10 days of gentamicin administration. Chloride concentration was higher only after 10 days (20.6 +/- 0.6 vs. 17.3 +/- 0.2 mmol/kg wet wt). Both cell potassium and phosphorus concentrations were diminished by 6 and 15, and by 8 and 25 mmol/kg wet wt after 7 and 10 days of treatment, respectively. In contrast, no major alterations in distal tubular cell electrolyte concentrations could be observed after either 7 or 10 days of gentamicin administration. As in proximal tubular cells, distal tubular cell phosphorus concentrations were, however, lowered by gentamicin treatment. These results clearly indicate that gentamicin exerts its main effect on proximal tubular cells. Decreased potassium and increased sodium and chloride concentrations were observed in proximal tubular cells exhibiting only mild histological damage prior to the onset of advanced tissue injury. Necrotic cells, on the other hand, showed widely variable intracellular electrolyte concentration patterns

  17. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

    Directory of Open Access Journals (Sweden)

    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  18. Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Paul Riccio

    2016-02-01

    Full Text Available Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM, combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret-/- or Etv4-/- sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret

  19. Strategies for glucose control in a study population with diabetes, renal disease and anemia (Treat study).

    Science.gov (United States)

    Weinrauch, Larry A; D'Elia, John A; Finn, Peter; Lewis, Eldrin F; Desai, Akshay S; Claggett, Brian L; Cooper, Mark E; McGill, Janet B

    2016-03-01

    Glucose lowering medication use among patients with type 2 diabetes and advanced renal disease (eGFRrenal disease advances, most of the oral anti-diabetic agents requiring renal clearance must be reduced or discontinued. The potential for prolonged hypoglycemia, fluid/volume overload and congestive heart failure may complicate medication choices. In order to evaluate patterns of glycemia management we describe glucose lowering medication use among patients with advanced renal disease and type 2 diabetes in a large multinational outcome trial designed to focus on patients with eGFRrenal function when compared with standard populations with normal kidney function. The use of multiple oral agents, or oral agents plus insulin was quite common. While gender did not appear to play a role in medication choices, there were significant regional variations. For example, oral agents were used more in North America compared with other regions (Latin America, Australia/Western Europe, Russia/Eastern Europe). Patients enrolled at more advanced ages were less likely to be on a regimen of rapid-acting insulin alone consistent with recommendations that suggest a preference for longer-acting preparations in the geriatric population (1). Higher degrees of obesity were associated more complex treatment regimens. Despite this population being at high risk for cardiovascular events, the use of beta blockers (50%), statins (64%) and aspirin (48%) were relatively low, especially in the group that did not require medications to achieve adequate glycemic control. Current attempts to compare strategies for diabetes therapy must control for baseline demographic group differences influencing treatment choice. Future recommendations for glycemic control in patients with Grade 3 or higher chronic kidney disease require additional studies, with matched populations. We suggest that evaluation of studies similar to TREAT will assist in determining the optimal therapeutic regimens for populations

  20. Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma.

    Science.gov (United States)

    Riss, Joseph; Khanna, Chand; Koo, Seongjoon; Chandramouli, Gadisetti V R; Yang, Howard H; Hu, Ying; Kleiner, David E; Rosenwald, Andreas; Schaefer, Carl F; Ben-Sasson, Shmuel A; Yang, Liming; Powell, John; Kane, David W; Star, Robert A; Aprelikova, Olga; Bauer, Kristin; Vasselli, James R; Maranchie, Jodi K; Kohn, Kurt W; Buetow, Ken H; Linehan, W Marston; Weinstein, John N; Lee, Maxwell P; Klausner, Richard D; Barrett, J Carl

    2006-07-15

    Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia.

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

    OpenAIRE

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

    2016-01-01

    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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-08-15

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

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

    International Nuclear Information System (INIS)

    Park, Seong Hoon; Yoon, Seong Kuk; Cho, Jin Han; Oh, Jong Young; Nam, Kyung Jin; Kwon, Hee Jin; Kim, Su Yeon; Kang, Myong Jin; Choi, Sun Seob; Sung, Gyung Tak

    2008-01-01

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

  4. An unusual cause of acute renal failure in sickle cell disease

    Science.gov (United States)

    Rockx, Marie-Antoinette; Gibson, Ian W.; Reslerova, Martina

    2009-01-01

    A young female with sickle cell disease was treated for biopsy-proven IgA nephropathy. Serum creatinine levels resolved to normal range, but a year later, she presented with oedema, hypertension and acute renal failure. A repeat renal biopsy showed acute-on-chronic thrombotic microangiopathy (TMA). We suggest that circulating microparticles could be a pathophysiological link between sickle cell disease and the development of renal TMA. This case emphasizes the importance of a further biopsy for acutely declining renal function, even when a definite diagnosis has been made from a previous biopsy. PMID:25949348

  5. Cyclosporine A induces senescence in renal tubular epithelial cells

    NARCIS (Netherlands)

    Jennings, Paul; Koppelstaetter, Christian; Aydin, Sonia; Abberger, Thomas; Wolf, Anna Maria; Mayer, Gert; Pfaller, Walter

    The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A (CsA) is well recognized. However, the mechanism of renal tubular toxicity is not yet fully elucidated. Chronic CsA nephropathy and renal organ aging share some clinical features, such as renal fibrosis and tubular

  6. T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma-Implications for Adoptive Cell Therapy

    DEFF Research Database (Denmark)

    Andersen, Rikke; Westergaard, Marie Christine Wulff; Kjeldsen, Julie Westerlin

    2018-01-01

    In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC...

  7. Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

    NARCIS (Netherlands)

    Smeets, B.; Angelotti, M.L.; Rizzo, P.; Dijkman, H.; Lazzeri, E.; Mooren, F.; Ballerini, L.; Parente, E.; Sagrinati, C.; Mazzinghi, B.; Ronconi, E.; Becherucci, F.; Benigni, A.; Steenbergen, E.; Lasagni, L.; Remuzzi, G.; Wetzels, J.F.M.; Romagnani, P.

    2009-01-01

    Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner

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

    Science.gov (United States)

    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. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  9. Lithium and renal and upper urinary tract tumors - results from a nationwide population-based study

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Gerds, Thomas Alexander; Feldt-Rasmussen, Bo

    2015-01-01

    OBJECTIVES: A recent alarming finding suggested an increased risk of renal tumors among long-term lithium users. The objectives of the present study were to estimate rates of renal and upper urinary tract tumors (RUT), malignant and benign, among individuals exposed to successive prescriptions...... for lithium, anticonvulsants, and other psychotropic agents used for bipolar disorder, and among unexposed individuals. METHODS: This was a nationwide, population-based longitudinal study including time-specific data from all individuals exposed to lithium (n = 24,272) or anticonvulsants (n = 386,255), all...... individuals with a diagnosis of bipolar disorder (n = 9,651), and a randomly selected sample of 1,500,000 from the Danish population. The study period was from 1995 to 2012, inclusive. Outcomes were hazard rate ratios (HR) for RUT in three groups: (i) combined malignant and benign, (ii) malignant, and (iii...

  10. Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

    Directory of Open Access Journals (Sweden)

    Christopher Williams

    2005-01-01

    Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

  11. Semiinvasive Aspergillosis Case Coexisting to Metastatic Renal Cell Cancer

    Directory of Open Access Journals (Sweden)

    Hatice Kilic

    2013-10-01

    Full Text Available Chronic necrotizing pulmonary aspergillosis (CNPA is defined as an cavity or mass lesion in the lung due to invasion of lung tissue by a fungus of the Aspergillosis species. It was described also as semiinvasive aspergillosis. Semiinvasive pulmonary aspergillosis is generally seen in patients with primer immunocompromised and it can be fatal in the event of late diagnose. We present 60 years old patient who had had renal cell cancer admitted to hospital with metastatic nodules in his chest X-ray and Thorax computed tomography. We have seen yellow colour of bronchial secretion in his bronchoscopy. Multipl mantar hyphae by A. Fumigatus was detected in his bronchial lavage cytology. Itrakonazol was administred to this patient. We review to this cases due to a semiinvasive aspergillosis was detected randomly when this case who had not both symptomatic and clinical sign by Aspergillosis is investigated.

  12. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. RESULTS: The median overall survival was 25.0 months (95% confidence...... interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate...

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-10-01

    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.

  15. Maslinic acid inhibits proliferation of renal cell carcinoma cell lines and suppresses angiogenesis of endothelial cells

    Directory of Open Access Journals (Sweden)

    Parth Thakor

    2017-03-01

    Full Text Available Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC remains a treatment-re-sistant 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.

  16. Computer approach to recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Kruk, Michal; Osowski, Stanislaw; Markiewicz, Tomasz; Slodkowska, Janina; Koktysz, Robert; Kozlowski, Wojciech; Swiderski, Bartosz

    2014-06-01

    To present a computerized system for recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma on the basis of microscopic images of the neoplasm cells in application of hematoxylin and eosin staining. The applied methods use combined gradient and mathematical morphology to obtain nuclei and classifiers in the form of support vector machine to estimate their Fuhrman grade. The starting point is a microscopic kidney image, which is subject to the advanced methods of preprocessing, leading finally to estimation of Fuhrman grade of cells and the whole analyzed image. The results of the numerical experiments have shown that the proposed nuclei descriptors based on different principles of generation are well connected with the Fuhrman grade. These descriptors have been used as the diagnostic features forming the inputs to the classifier, which performs the final recognition of the cells. The average discrepancy rate between the score of our system and the human expert results, estimated on the basis of over 3,000 nuclei, is below 10%. The obtained results have shown that the system is able to recognize 4 Fuhrman grades of the cells with high statistical accuracy and agreement with different expert scores. This result gives a good perspective to apply the system for supporting and accelerating the research of kidney cancer.

  17. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

    OpenAIRE

    Kyoung-jin Min; Ju-Ock Nam; Taeg Kyu Kwon

    2017-01-01

    Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (...

  18. Renal Cell Carcinoma of the Kidney with Synchronous Ipsilateral Transitional Cell Carcinoma of the Renal Pelvis

    Directory of Open Access Journals (Sweden)

    Dogan Atilgan

    2013-01-01

    Full Text Available A 73-year-old man was admitted to our clinic with flank pain and gross macroscopic hematuria. Radiologic examination revealed a solid mass in the left kidney and additionally another mass in the ureteropelvic junction of the same kidney with severe hydronephrosis. Left nephroureterectomy with bladder cuff removel was performed, and histopathological evolution showed a Fuhrman grade 3 clear cell type RCC with low-grade TCC of the pelvis.

  19. Heavy metals toxicity after acute exposure of cultured renal cells. Intracellular accumulation and repartition

    International Nuclear Information System (INIS)

    Khodja, Hicham; Carriere, Marie; Avoscan, Laure; Gouget, Barbara

    2005-01-01

    Lead (Pb), cadmium (Cd) and uranium (U) present no known biological function but are toxic in various concentration ranges. Pb and Cd lead generally to nephrotoxicity consisting in proximal renal tubular dysfunction and accumulation while U has been reported to induce chemical kidney toxicity, functional and histological damages being as well mainly observed in proximal tubule cells. This work address the question of Cd, Pb, and U cytotoxicity, intracellular accumulation and repartition after acute intoxication of renal proximal tubule epithelial cells. After cells exposure to different concentrations of metals for various times, morphological changes were observed and intracellular concentrations and distributions of toxic metals were specified by PIXE coupled to RBS. Cell viability, measured by biochemical tests, was used as toxicity indicator. A direct correlation between cytotoxicity and intracellular accumulation in renal epithelial cells have been established. Finally, intracellular Pb and U localizations were detected while Cd was found to be uniformly distributed in renal cells. (author)

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

    Science.gov (United States)

    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

    2018-03-01

    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 (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. Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

    International Nuclear Information System (INIS)

    Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming

    2007-01-01

    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 β-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 β-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

  2. A Rare Case of a Renal Cell Carcinoma Confined to the Isthmus of a Horseshoe Kidney

    Directory of Open Access Journals (Sweden)

    Michael Kongnyuy

    2015-01-01

    Full Text Available Horseshoe kidney (HSK is the most common renal anomaly. Reports of the incidence of renal cell carcinoma (RCC in HSK are conflicting. Very few cases of isthmus-located RCC have been reported in the literature. We report a unique case of an isthmus-located RCC. Proper vascular and tumor imaging prior to surgery is key to successful tumor removal.

  3. Clinicopathological characteristics of renal cell carcinoma in a dialysis patient

    International Nuclear Information System (INIS)

    Hayashida, Yushi; Sumitani, Haruo

    2009-01-01

    In order to clarify the clinicopathological features of renal cell carcinoma (RCC) occurring in chronic hemodialysis patients, we analyzed patient demographics, hemodialysis duration, pathological characteristics of the tumors and prognosis of these patients. We retrospectively reviewed the record of 16 patients who had undergone radical nephrectomy for RCC at Kawashima Hospital between November 1994 and December 2007. They ranged in age from 32 to 82 years old (mean age, 55.0), and comprised 14 males and 2 females. All the patients were clinical stage I. As for the underlying disease which caused renal failure, chronic glomerulonephritis was noted in 12 patients and diabetes mellitus was noted in 1 patient. The causes in 3 patients were unknown. The duration of hemodialysis ranged from 1 to 226 months, (90 months on average). As for the main diagnostic methods, CT was performed in 14 cases. Two patients demonstrated macroscopic hematuria Acquired cystic disease of the kidney (ACDK) was present in 10 patients (68.8%). Patients were divided two groups; patients who had undergone open surgery (group 1, N=7) and patients who had undergone retroperitoneoscopic surgery (group 2, N=9). The following factors were analyzed: operation time, bleeding volume, postoperative complications, hospitalization. Nephrectomy was performed for the right kidney in 8 patients, and for the left kidney in 8 patients. Operation time ranged from 90 to 150 minutes (average, 111 min), in group 1, and from 80 to 284 minutes (average, 146 min), in group 2. Bleeding volume ranged from 10 to 170 ml (average, 72 ml), in group 1, and from 10 to 50 ml (average, 15 ml), in group 2. Complications of nephrectomy were observed in 6 patients, but all were minor problems. As for hospitalization, in group 1 it was 20 days and in group 2 it was 12 days. Fifteen patients survived and are tumor free. One patient died of causes unrelated to RCC. (author)

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

    Science.gov (United States)

    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

  5. Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kenan Ashouri

    2015-09-01

    Full Text Available Von Hippel-Lindau syndrome (VHLS is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves.  This review will discuss the key aspects of the current management of VHLS.

  6. [Renal cell carcinoma producing erythrocytosis due to inappropriate production of erythropoietin].

    Science.gov (United States)

    Villanueva-Gimeno, M M; Vicario-Bermúdez, J M; Fonseca-López, Ch; Caballero-Castro, J P; Zabala-López, S I; Sánchez-Elipe, M A; González-Gómez, N

    2013-01-01

    Erythrocytosis, or polycythaemia, is an increase, in absolute terms, of the erythrocyte mass. The most common solid tumour related to this phenomenon is renal cell carcinoma, which can produce erythrocytosis by increasing erythropoietin production. About 30% of symptomatic renal cell carcinomas are diagnosed due to the appearance of a paraneoplastic syndrome. Polycythaemia is one of these. Surgery, (radical or partial nephrectomy), is the treatment of choice in renal cell carcinoma and helps to keep the erythrocytosis situation under control. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  7. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

    Science.gov (United States)

    Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

    2017-01-01

    Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

  8. Understanding familial and non-familial renal cell cancer.

    Science.gov (United States)

    Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J M; Eleveld, Marc J; Martens, Gerard J M; Weterman, Marian A J; van Kessel, Ad Geurts

    2002-10-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is still pending. Additionally, a novel role for constitutional chromosome 3 translocations as risk factors for conventional RCC development is rapidly emerging. Also, several candidate loci have been mapped to other chromosomes in both familial and non-familial RCCs of distinct histologic subtypes. The MET gene on chromosome 7, for example, was found to be involved in both forms of papillary RCC. A PRCC-TFE3 fusion gene is typically encountered in t(X;1)-positive non-familial papillary RCCs and results in abrogation of the cell cycle mitotic spindle checkpoint in a dominant-negative fashion, thus leading to RCC. Together, these data turn human RCC into a model system in which different aspects of both familial and non-familial syndromes may act as novel paradigms for cancer development.

  9. The use of prognostic factors in metastatic renal cell carcinoma.

    Science.gov (United States)

    Li, Haoran; Samawi, Haider; Heng, Daniel Y C

    2015-12-01

    Over the last decade, the treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved tremendously. The outcome of patients with mRCC has been improved since the advent of targeted therapy. In this review, we address the use of prognostic schema in the era of targeted treatment. This article summarizes the current available prognostic models and the evidence to support their use in clinical settings. Prognostic models can help guide clinicians in their decision making, as they have been validated in the first- and second-line targeted therapy settings as well as in non-clear cell mRCC. Prognostic factors are important in patient counseling, clinical trial stratification, and therapy planning. Very selected favorable-risk patients with minimal bulk and slow-growing disease could potentially be observed before needing treatment. Patients with poor-risk disease may be eligible for treatment with temsirolimus. Patients with a very poor prognosis may not be suitable candidates for cytoreductive nephrectomy. New biomarkers are on the horizon, though their roles need to be validated and their additive contribution to improve existing prognostic models examined. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Coffee consumption and risk of renal cell carcinoma.

    Science.gov (United States)

    Antwi, Samuel O; Eckel-Passow, Jeanette E; Diehl, Nancy D; Serie, Daniel J; Custer, Kaitlynn M; Arnold, Michelle L; Wu, Kevin J; Cheville, John C; Thiel, David D; Leibovich, Bradley C; Parker, Alexander S

    2017-08-01

    Studies have suggested an inverse association between coffee consumption and risk of renal cell carcinoma (RCC); however, data regarding decaffeinated coffee are limited. We conducted a case-control study of 669 incident RCC cases and 1,001 frequency-matched controls. Participants completed identical risk factor questionnaires that solicited information about usual coffee consumption habits. The study participants were categorized as non-coffee, caffeinated coffee, decaffeinated coffee, or both caffeinated and decaffeinated coffee drinkers. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for multiple risk factors for RCC. Compared with no coffee consumption, we found an inverse association between caffeinated coffee consumption and RCC risk (OR 0.74; 95% CI 0.57-0.99), whereas we observed a trend toward increased risk of RCC for consumption of decaffeinated coffee (OR 1.47; 95% CI 0.98-2.19). Decaffeinated coffee consumption was associated also with increased risk of the clear cell RCC (ccRCC) subtype, particularly the aggressive form of ccRCC (OR 1.80; 95% CI 1.01-3.22). Consumption of caffeinated coffee is associated with reduced risk of RCC, while decaffeinated coffee consumption is associated with an increase in risk of aggressive ccRCC. Further inquiry is warranted in large prospective studies and should include assessment of dose-response associations.

  11. Novel immunotherapy approaches for metastatic urothelial and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhiying Shao

    2016-10-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC and urothelial carcinoma (UC remains a major challenge. Past research has implicated the immune system in tumor surveillance of both malignancies, leading to the application of immunotherapy agents for both cancers. Among them, the most promising agents are the checkpoint blockade drugs, such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, programmed death receptor 1 (PD-1, and PD-1 ligand (PD-L1. In normal physiology, these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions, which is pivotal for maintaining self-tolerance. However, tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response, leading to disease progression and metastasis. Thus, there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC. To date, nivolumab (anti-PD-1 and atezolizumab (anti-PD-L1 have been approved for the treatment of metastatic RCC and UC, respectively. Despite these successes, challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach. In this report, we review existing data and research on immunotherapy in metastatic RCC and UC.

  12. Identification and Characterization of Renal Cell Carcinoma Gene Markers

    Directory of Open Access Journals (Sweden)

    Louis S. Liou

    2007-01-01

    Full Text Available 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 identifi ed 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 categorie at a signifi cance 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.

  13. Metastatic renal cell carcinoma – a case report

    Directory of Open Access Journals (Sweden)

    Grzegorz Wróbel

    2017-09-01

    Full Text Available Renal cell carcinoma (RCC is not a single uniform entity but a group of related neoplasms in which the histologic findings, cytogenetic abnormalities, biologic behavior and imaging appearances of the tumors are subtype dependent. PET-CT is the fusion of functional and anatomic information acquired almost simultaneously that lets us see the body and disease in a way that is diagnostically very powerful. The case concerns the result imaging 18F-fluorodeoxyglucose positron emission tomography (PET-CT to patient 47 years old (women is diagnosed with numerous changes in both lungs, the liver and the skeletal system in the abdominal lymph nodes. Primary change in left kidney is indicated. Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Functional imaging, particularly with PET–CT, might improve the accuracy of diagnosis and provide essential information that could allow clinicians to make more appropriate therapeutic decisions than they previously could without this technique.

  14. Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk.

    Directory of Open Access Journals (Sweden)

    Todd M Gibson

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Quivy A

    2013-04-01

    Full Text Available Amandine Quivy,1,2 Amaury Daste,1 Asma Harbaoui,1 Sophie Duc,2,4 Jean-Christophe Bernhard,2,3 Marine Gross-Goupil,1 Alain Ravaud1,2 1Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital, Bordeaux, France; 2University of Bordeaux 2 (Victor Ségalen, Bordeaux, France; 3Department of Urology, Hôpital Pellegrin, Bordeaux University Hospital, Bordeaux, France; 4Department of Geriatrics, Hôpital Saint-André, Bordeaux University Hospital, Bordeaux, France Abstract: 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

  16. Application of modified R.E.N.A.L. nephrometry score system in evaluating the retroperitoneal partial nephrectomy for T1 renal cell carcinoma.

    Science.gov (United States)

    Wang, Qinzhang; Qian, Biao; Li, Qiang; Ni, Zhao; Li, Yinglong; Wang, Xinmin

    2015-01-01

    This study aims to investigate the application of the modified R.E.N.A.L. nephrometry score system in evaluating the operation difficulty of retroperitoneal partial nephrectomy in T1 renal cell carcinoma patients. A total of 52 patients with T1 renal cell carcinoma were enrolled. They all had retroperitoneal partial nephrectomy. Their clinical data was retrospectively analyzed. R.E.N.A.L. nephrometry score system was modified based on the features of retroperitoneal partial nephrectomy. The specificity, sensitivity and Youden index were compared between R.E.N.A.L. nephrometry score system and the modified R.E.N.A.L. nephrometry score system. The effect of the modified R.E.N.A.L. nephrometry score system on perioperative outcomes was analyzed. Three degrees of operation difficulty were defined by the modified R.E.N.A.L. nephrometry score system, which included the low, medium and high degree of operation difficulty. The specificity, sensitivity and Youden index of the modified R.E.N.A.L. nephrometry score system were better than those of the original R.E.N.A.L. nephrometry score system. Compared with low degree of operation difficulty, patients with medium and high degree of operation difficulty had significantly higher levels of operative time, warm ischemia time, and intraoperative blood loss (P system has a good effect in evaluating the operation difficulty of retroperitoneal partial nephrectomy.

  17. The proximal tubular cell, a key player in renal damage

    NARCIS (Netherlands)

    Timmeren, Mirjan Miranda van

    2008-01-01

    A decline in renal function is associated with the degree of proteinuria and with histological findings of glomerulosclerosis and interstitial fibrosis. Proteinuria is not only a marker of renal damage, but ultrafiltered proteins can be toxic to the kidney, thereby contributing to

  18. Mass spectrometry-based analysis of the HLA-ligandomes of renal cell carcinoma and benign renal tissue

    OpenAIRE

    Rabsteyn, Armin

    2018-01-01

    Peptide vaccination is a promising immunotherapeutic approach for the treatment of malignancies. In this project, the unique opportunity to analyze HLA ligandomes of samples from tumor and adjacent benign tissue of renal cell carcinoma (RCC) patients by mass spectrometry was given. This allowed for the establishment of a novel approach of antigen definition by comparative profiling of malignant and benign HLA ligandomes. Analyses were performed for HLA class I and II of tumor and benign tissu...

  19. Rate of renal cell carcinoma subtypes in different races

    Directory of Open Access Journals (Sweden)

    Alexander Sankin

    2011-02-01

    Full Text Available PURPOSE: We sought to identify racial differences among histological subtypes of renal cell carcinoma (RCC between black and non-black patients in an equal-access health care system. MATERIALS AND METHODS: We established a multi-institutional, prospective database of patients undergoing partial or radical nephrectomy between January 1, 2000 and Sept 31, 2009. For the purposes of this study, data captured included age at diagnosis, race, tumor size, presence of lymphovascular invasion, presence of capsular invasion, margin status, and tumor histology. RESULTS: 204 kidney tumors were identified (Table-1. Of these, 117 (57.4% were in black patients and 87 (42.6% were in non-black patients. Age at surgery ranged from 37 to 87 with a median of 62. Tumor size ranged from 1.0 to 22.0 cm with a median of 5.0 cm. Overall, tumors were composed of clear cell RCC in 97 cases (47.5%, papillary RCC in 65 cases (31.9%, chromophobe RCC in 13 cases (6.4%, collecting duct/medullary RCC in 2 cases (1.0%, RCC with multiple histological subtypes in 8 cases (3.9%, malignant tumors of other origin in 6 cases (2.9%, and benign histology in 13 cases (6.4%. Among black patients, papillary RCC was seen in 56 cases (47.9%, compared to 9 cases (10.3% among non-black patients (p < 0.001 (Table-2. Clear cell RCC was present in 38 (32.5% of black patients and in 59 (67.8% of non-blacks (p < 0.001. CONCLUSIONS: In our study, papillary RCC had a much higher occurrence among black patients compared to non-black patients. This is the first study to document such a great racial disparity among RCC subtypes.

  20. Combined effect of angioinfarction with immunotherapy in patients with stage IV renal cell carcinoma

    International Nuclear Information System (INIS)

    Oh, Joo Hyeong; Yoon, Yup; Jeong, Yu Mee; Ko, Young Tae; Chang, Sung Goo

    1994-01-01

    To assess the combined effectiveness of angioinfarction and immunotherapy for improving survival in patients with stage IV renal cell carcinoma. During the past 3 years, 13 patients of stage IV renal cell carcinoma were treated with angioinfarction and immunotherapy. Angioinfarction was performed on these 13 patients using absolute ethanol and occlusive balloon catheter. After angioinfarction, Interferon alpha was used for immunotherapy. For our analysis, 12 control patients of stage IV renal cell carcinoma without treatment were included in the study. Survival has been calculated according to the Kaplan and Meier method. The 1 year survival rate and median survival time in patients treated with angioinfarction and immunotherapy, were 46% and 13 months and in patients without treatment, 16% and 4 months, respectively. The combined treatment of angioinfarction and immunotherapy is of considerable value for improving survival in patients with stage IV renal cell carcinoma

  1. Synchronous sigmoid and caecal cancers together with a primary renal cell carcinoma.

    LENUS (Irish Health Repository)

    Bhargava, A

    2012-06-01

    Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms.

  2. Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

    Science.gov (United States)

    Johnston, Kimberly A; Westover, Angela J; Rojas-Pena, Alvaro; Buffington, Deborah A; Pino, Christopher J; Smith, Peter L; Humes, H David

    2017-11-01

    Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 10 8 renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

    Science.gov (United States)

    Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

    2017-09-27

    The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  4. The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney

    NARCIS (Netherlands)

    Duns, Gerben; van den Berg, Anke; van Dijk, Marcory C. R. F.; van Duivenbode, Inge; Giezen, Cor; Kluiver, Joost; van Goor, Harry; Hofstra, Robert M. W.; van den Berg, Eva; Kok, Klaas

    Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to

  5. MR imaging of renal cell carcinoma: associations among signal intensity, tumor enhancement, and pathologic findings.

    OpenAIRE

    Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio

    2003-01-01

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics ...

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

    Science.gov (United States)

    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.

  7. Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

    Science.gov (United States)

    Gravis, Gwenaelle; Faure, Marjorie; Rybikowski, Stanislas; Dermeche, Slimane; Tyran, Marguerite; Calderon, Benoit; Thomassin, Jeanne; Walz, Jochen; Salem, Naji

    2015-11-01

    Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.

  8. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma

    International Nuclear Information System (INIS)

    Wersaell, Peter J.; Blomgren, Henric; Lax, Ingmar; Kaelkner, Karl-Mikael; Linder, Christina; Lundell, Goeran; Nilsson, Bo; Nilsson, Sten; Naeslund, Ingemar; Pisa, Pavel; Svedman, Christer

    2005-01-01

    Background and purpose: We investigated the results of using stereotactic radiotherapy (SRT) for 58 patients with renal cell carcinomas (RCC) who were evaluated restrospectively for response rates, local control rates and side effects. Patients and methods: From October 1997 to January 2003, 50 patients suffering from metastatic RCC and eight patients with inoperable primary RCC received high-dose fraction SRT while placed in a stereotactic body-frame. The most common dose/fractionation schedules used were 8 Gyx4, 10 Gyx4 and 15 Gyx3 during approximately 1 week. Results: SRT-treated tumor lesions regressed totally in 30% of the patients at 3-36 months, whereas 60% of the patients had a partial volume reduction or no change after a median follow-up of 37 months (SD 17.4) for censored and 13 months (SD 12.9) for uncensored patients. Side effects were generally mild. Of 162 treated tumors, only three recurred, yielding a local control rate of 90-98%, considering the 8% non-evaluable sites as defined here. For patients with one to three metastases, the time to new spread was 9 months. Conclusions: Our use of SRT for patients with primary and metastatic RCC yielded a high local control rate with low toxicity. Patients with one to three metastases, local recurrences after nephrectomy or inoperable primary tumors benefited the most, i.e. had fewer distant recurrences (13/23) and longer survival times compared to patients with >3 metastases (24/27 recurrences)

  9. Update on contemporary management of clinically localized renal cell carcinoma.

    Science.gov (United States)

    Jorns, J J; Thiel, D D; Castle, E P

    2012-12-01

    Renal cell carcinoma (RCC) continues to increase in incidence with the largest increase manifesting in small, organ-confined tumors. This review outlines the epidemiology and current data pertaining to the management of clinically-localized RCC. In this manuscript, the current data outlining the benefit of nephron sparing to the overall survival of the patient is described. The data pertaining to minimally invasive nephron sparing is also explained in detail. From laparoscopic and robotic partial nephrectomy to watchful waiting and percutaneous ablation, the urologist is continually assaulted with new data for the management of clinically-localized RCC. The data can be confusing, and much of it is conflicting. The addition of new scoring systems or nomograms may aid in predicting which therapy would be most beneficial in certain patient groups. New scoring systems may also predict the difficulty of surgical resection and predict surgical complications. The limitations of the data pertaining to the management of clinically-localized RCC are also outlined.

  10. Medical image of the week: calvairial renal cell mestastases

    Directory of Open Access Journals (Sweden)

    Witten A

    2016-01-01

    Full Text Available No abstract available. Article truncated at 150 words. A 57-year-old woman with past medical history significant for clear cell renal carcinoma and radical nephrectomy 9 years prior was admitted to our hospital for headache and left hemiparesis with associated numbness. Symptoms were progressive and had begun about 5 days prior to her presenting to our emergency department. Neurologic exam was significant for reduced strength in her left upper and lower extremities as well as well as sensory deficit to fine touch and vibratory sensation in her left arm. Her gait was unsteady and she was unable to ambulate without assistance. Her right calvarium was grossly enlarged and asymmetrical with softening of the underlying boney structures. MRI of the brain showed a 10 cm x 5 cm mass that was obliterating the calvarium and invading the dura mater (Figure 1. There was mass effect with shift of the midline structures from right to left by approximately 6.5 mm (Figures ...

  11. Pattern of failure following surgical resection of renal cell carcinoma

    International Nuclear Information System (INIS)

    Aref, I.; Bociek, G.; Salhani, D.

    1996-01-01

    Purpose/objective: To identify the pattern of failure in patients with resected renal cell carcinoma (RCC). Materials and Methods: The records of 116 patients with unilateral non-metastatic RCC, who were treated with definitive surgery and referred to the Ottawa Regional Cancer Centre between 1977 and 1988, were reviewed. Distribution by stage included: T1 = 3 patients, T2 = 42 patients, T3 =71 patients. The median follow-up was 44 months, with a range of 4-267 months. Results: Loco-regional failure (LRF) developed in 8 patients, yielding a 7-year actuarial incidence of 8% for LRF, as first event. Nine patients developed local or regional recurrence + distant failure, and 58 patients had distant metastases only. Seven-year actuarial incidence of distant failure was 55%. The overall 7-year actuarial survival rate was 40%, and cause-specific survival was 45%. Conclusion: LRF was rare following nephrectomy. This data does not support the role of adjuvant radiation therapy in this disease

  12. Is post-operative radiation for renal cell carcinoma justified?

    International Nuclear Information System (INIS)

    Aref, Ibrahim; Bociek, R. Gregory; Salhani, Douglas

    1997-01-01

    Purpose: To identify the pattern of failure in patients with resected renal cell carcinoma (RCC). Materials and methods: The records of 116 patients with unilateral, non-hematogenous metastatic RCC who were treated with definitive surgery and referred to the Ottawa Regional Cancer Centre between 1977 and 1988 were reviewed. Distribution by stage included T1 (3 patients), T2 (42 patients) and T3 (71 patients). The median follow-up was 44 months, with a range of 4-267 months. Results: Local regional failure (LRF) developed in 8 patients. Nine patients developed local or regional recurrence, plus distant failure. Fifty-eight patients had distant metastases (DM) only. The 7-year actuarial rate for LRF and DM were 12%, and 67%, respectively. The overall 7-year actuarial survival rate was 35%, and cause-specific survival was 42%. Conclusions: LRF alone is rare following nephrectomy. DM is the main pattern of failure. This data does not support the role of adjuvant radiation therapy in this disease

  13. Immunotherapy in Metastatic Renal Cell Carcinoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Rachna Raman

    2015-01-01

    Full Text Available Localized renal cell carcinoma (RCC is often curable by surgery alone. However, metastatic RCC is generally incurable. In the 1990s, immunotherapy in the form of cytokines was the mainstay of treatment for metastatic RCC. However, responses were seen in only a minority of highly selected patients with substantial treatment-related toxicities. The advent of targeted agents such as vascular endothelial growth factor tyrosine kinase inhibitors VEGF-TKIs and mammalian target of rapamycin (mTOR inhibitors led to a change in this paradigm due to improved response rates and progression-free survival, a better safety profile, and the convenience of oral administration. However, most patients ultimately progress with about 12% being alive at 5 years. In contrast, durable responses lasting 10 years or more are noted in a minority of those treated with cytokines. More recently, an improved overall survival with newer forms of immunotherapy in other malignancies (such as melanoma and prostate cancer has led to a resurgence of interest in immune therapies in metastatic RCC. In this review we discuss the rationale for immunotherapy and recent developments in immunotherapeutic strategies for treating metastatic RCC.

  14. Functional significance of erythropoietin in renal cell carcinoma

    International Nuclear Information System (INIS)

    Morais, Christudas; Johnson, David W; Vesey, David A; Gobe, Glenda C

    2013-01-01

    One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion

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

    Science.gov (United States)

    Tuggle, Benjamin 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

  16. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  17. HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Ramakrishnan, Swathi; Ku, ShengYu; Ciamporcero, Eric; Miles, Kiersten Marie; Attwood, Kris; Chintala, Sreenivasulu; Shen, Li; Ellis, Leigh; Sotomayor, Paula; Swetzig, Wendy; Huang, Ray; Conroy, Dylan; Orillion, Ashley; Das, Gokul; Pili, Roberto

    2016-01-01

    Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown. Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2α knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student’s T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival. Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2α is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ERα) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated α-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset. Taking together, these results

  18. Semidirect differentiation as a histopathological prognostic parameter in renal cell carcinoma

    International Nuclear Information System (INIS)

    Bartos, V.; Zacharova, O.; Pokorny, D.; Mraz, R.; Mikulas, J.; Laurinc, P.

    2012-01-01

    Renal cell carcinoma (RCC) is currently one of the most frequent urological malignancies. One of the important histological findings, which reflect biological behaviour of RCC and also provide significant prognostic data are sarcomatoid changes of tumor. In our paper we evaluated the incidence of sarcomatoid changes in renal cell carcinomas and their relationship with other clinico-pathological parameters. A study group consisted of 159 cancers from 157 patients (95 men, 62 women) in the age rage from 18 to 82 years. Out of all cases we found 18 carcinomas (11.3%) having varying degrees of sarcomatoid changes. These tumors were obtained from 18 subjects (11 men, 7 women) between 45 and 82 years of age (mean age 69.1 years). Among them, there were 13 conventional clear cell RCCs, 1 papillary RCC, 2 unclassified RCCs and 2 carcinomas, that entirely consisted of sarcomatoid tissue, were classified as sarcomatoid RCCs. Histologically, sarcomatoid component predominantly composed of spindle cells population with varying degrees of anaplasia and sometimes exhibited rhabdoid features. Six cases corresponded to the pathological stage limited to the kidney (pT1 and pT2) and ten cases were diagnosed in pathological stage with extrarenal propagation (pT3 and pT4). Four patients had metastases in the regional lymph nodes. Almost all cancers showed necrosis. Since sarcomatoid changes in RCC are usually associated with negative prognostic parameters and much less favourable prognosis of disease, if present, pathologist must describe them in a biopsy report. From a clinical point of view, these patients require more careful follow-up, as the literature data indicate the majority of them have metastases at the time of diagnosis. (author)

  19. Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue sarcoma patients: opportunities for dose optimization.

    Science.gov (United States)

    Verheijen, R B; Swart, L E; Beijnen, J H; Schellens, J H M; Huitema, A D R; Steeghs, N

    2017-12-01

    Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a relationship between pazopanib trough concentrations (C min ) and treatment efficacy. The aim of this study was to explore the pharmacokinetics and exposure-survival relationships of pazopanib in a real-world patient cohort. Renal cell cancer and soft tissue sarcoma patients who had at least one pazopanib plasma concentration available were included. Using calculated C min values and a threshold of > 20 mg/L, univariate and multivariate exposure-survival analyses were performed. Sixty-one patients were included, of which 16.4% were underexposed (mean C min   20 mg/L was related to longer progression free survival in renal cell cancer patients (34.1 vs. 12.5 weeks, n = 35, p = 0.027) and the overall population (25.0 vs. 8.8 weeks, n = 61, p = 0.012), but not in the sarcoma subgroup (18.7 vs. 8.8 weeks, n = 26, p = 0.142). In multivariate analysis C min  > 20 mg/L was associated with hazard ratios of 0.25 (p = 0.021) in renal cancer, 0.12 (p = 0.011) in sarcoma and 0.38 (p = 0.017) in a pooled analysis. This study confirms that pazopanib C min  > 20 mg/L relates to better progression free survival in renal cancer and points towards a similar trend in sarcoma patients. C min monitoring of pazopanib can help identify patients with low C min for whom individualized treatment at a higher dose may be appropriate.

  20. Mecanismos del daño celular en la insuficiencia renal aguda Mechanisms of cell damage in acute renal failure

    Directory of Open Access Journals (Sweden)

    José Martínez

    1989-01-01

    Full Text Available

    Los mecanismos del da no celular en la insuficiencia renal aguda Incluyen alteraciones en la producción de energía, la permeabilidad celular y el transporte de calcio. Dichas alteraciones producen cambios progresivos en la estructura celular que pueden ser reversibles si desaparece la causa que llevó a la falla renal, excepto cuando se alcanza la fase final de la lesión de la membrana y se llega a necrosis celular. Este mismo fenómeno probablemente ocurre tambIén en situaciones clínicas.

    The mechanisms of cellular damage In acute renal failure Include alterations In energy production, cell membrane permeability and calcium transport. These changes lead to progressive damage of the whole cellular structure which In general can be reversible If the precipitating cause disappears, except when the final stages of cell membrane lesion take place and cellular necrosis has occurred. This phenomenon probably applies for the clinical settling as well.

  1. Renal cell carcinoma as a cause of iron deficiency anemia

    African Journals Online (AJOL)

    Amar A. Dowd

    derived from the various parts of the nephron (epithelium or renal tubules) and possessing ... [3] is hematuria, flank pain, and an abdominal mass, similar to bloat- ... mass in the right kidney implicating its anterior aspect, measuring 62 × 48 mm.

  2. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function

    Directory of Open Access Journals (Sweden)

    Li Y

    2017-11-01

    Full Text Available Yan Li,1 Xiaomin Wang,2 Edward O’Mara,1 Meletios A Dimopoulos,3 Pieter Sonneveld,4 Katja C Weisel,5 Jeffrey Matous,6 David S Siegel,7 Jatin J Shah,8 Elisabeth Kueenburg,9 Lars Sternas,9 Chloe Cavanaugh,9 Mohamed Zaki,9 Maria Palmisano,1 Simon Zhou1 1Translational Development and Clinical Pharmacology, Celgene Corporation, Summit, NJ, USA; 2Non-Clinical Development and Drug Metabolism and Pharmacokinetics, Celgene Corporation, Summit, NJ, USA; 3Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 5Department of Hematology, University Hospital Tübingen, Tübingen, Germany; 6Department of Hematology/Oncology, Colorado Blood Cancer Institute, Denver, CO, USA; 7Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA; 8Department of Lymphoma/Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA; 9Global Clinical R&D, Celgene Corporation, Summit, NJ, USA Abstract: Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide

  3. EphA2 Is a Potential Player of Malignant Cellular Behavior in Non-Metastatic Renal Cell Carcinoma Cells but Not in Metastatic Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Cho, Min Chul; Cho, Sung Yong; Yoon, Cheol Yong; Lee, Seung Bae; Kwak, Cheol; Kim, Hyeon Hoe; Jeong, Hyeon

    2015-01-01

    To investigate the role of EphA2 in malignant cellular behavior in renal cell carcinoma (RCC) cells and whether FAK/RhoA signaling can act as downstream effectors of EphA2 on RCC cells. Expression of EphA2 protein in non-metastatic RCC (Caki-2 and A498), metastatic RCC cells (Caki-1 and ACHN), HEK-293 cells and prostate cancer cells (PC-3 and DU-145; positive controls of EphA2 expression) was evaluated by Western blot. Changes in mRNA or protein expression of EphA2, FAK or membrane-bound RhoA following EphA2, FAK or RhoA small interfering RNA (siRNA) transfection were determined by reverse transcription polymerase chain reaction or Western blot. The effect of siRNA treatment on cellular viability, apoptosis and invasion was analyzed by cell counting kit-8, Annexin-V and modified Matrigel-Boyden assays, respectively. In all RCC cell lines, the expression of EphA2 protein was detectable at variable levels; however, in HEK-293 cells, EphA2 expression was very low. Treatment with EphA2 siRNA significantly reduced the expression of EphA2 mRNA and protein in all RCC cell lines. For non-metastatic RCC cells (Caki-2 and A498) but not metastatic RCC cells (Caki-1 and ACHN), cellular viability, invasiveness, resistance to apoptosis, expression of membrane-bound RhoA protein and FAK phosphorylation were significantly decreased in EphA2 siRNA-treated cells compared to the control. In non-metastatic RCC cells, FAK siRNA significantly attenuated the invasiveness, resistance to apoptosis, as well as expression of membrane-bound RhoA protein without changing protein expression of EphA2. RhoA siRNA significantly decreased the malignant cellular behavior and expression of membrane-bound RhoA protein without changing EphA2 protein expression or FAK phosphorylation. Our data provide the first functional evidence that the EphA2/FAK/RhoA signaling pathway plays a critical role in the malignant cellular behavior of RCC and appears to be functional particularly in the early stage of

  4. Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features.

    Science.gov (United States)

    Lu, Qing; Li, Cui-xian; Huang, Bei-jian; Xue, Li-yun; Wang, Wen-ping

    2015-02-01

    To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p 97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.

  5. Oncology Gold Standard™ practical consensus recommendations 2016 for treatment of advanced clear cell renal cell carcinoma.

    Science.gov (United States)

    Batra, U; Parikh, P M; Prabhash, K; Tongaonkar, H B; Chibber, P; Dabkara, D; Deshmukh, C; Ghadyalpatil, N; Hingmire, S; Joshi, A; Raghunath, S K; Rajappa, S; Rajendranath, R; Rawal, S K; Singh, Manisha; Singh, R; Somashekhar, S P; Sood, R

    2016-01-01

    The Oncology Gold Standard (OGS) Expert Group on renal cell carcinoma (RCC) developed the consensus statement to provide community oncologists practical guidelines on the management of advanced clear cell (cc) RCC using published evidence, practical experience of experts in real life management, and results of a nationwide survey involving 144 health-care professionals. Six broad question categories containing 33 unique questions cover major situations in the routine management of RCC. This document serves as a ready guide for the standard of care to optimize outcome. The table of "Take Home Messages" at the end is a convenient tool for busy practitioners.

  6. Oncology Gold Standard™ practical consensus recommendations 2016 for treatment of advanced clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    U Batra

    2016-01-01

    Full Text Available The Oncology Gold Standard (OGS Expert Group on renal cell carcinoma (RCC developed the consensus statement to provide community oncologists practical guidelines on the management of advanced clear cell (cc RCC using published evidence, practical experience of experts in real life management, and results of a nationwide survey involving 144 health-care professionals. Six broad question categories containing 33 unique questions cover major situations in the routine management of RCC. This document serves as a ready guide for the standard of care to optimize outcome. The table of "Take Home Messages" at the end is a convenient tool for busy practitioners.

  7. Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

    Directory of Open Access Journals (Sweden)

    Nadine Gelbrich

    2017-01-01

    Full Text Available Objective. Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods. Four renal cell cancer (RCC cell lines (Caki-1, 786-O, RCC4, and A498 and a nonmalignant renal cell line (RC-124 were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany, and expression profiles were compared. Results. Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion. This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.

  8. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  9. Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma

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    Fernando G. Abarzua-Cabezas

    2015-02-01

    Full Text Available Purpose To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. Materials and Methods We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR was calculated according to the Modification of Diet in Renal Disease equation. Results The majority (85% of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%. Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months. Conclusion While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

  10. Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age : implications for surveillance

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Badeloe, Sadhanna; Oosting, Sjoukje F.; Hovenga, Sjoerd; Semmelink, Harry J. F.; van Moorselaar, R. Jeroen A.; van Waesberghe, Jan Hein; Mensenkamp, Arjen R.; Menko, Fred H.

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation

  11. Long-term reversibility of renal dysfunction associated to light chain deposition disease with bortezomib and dexamethasone and high dose therapy and autologous stem cell transplantation

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    Tomás J. González-López

    2011-11-01

    Full Text Available A 63-year-old woman presented with progressive renal insufficiency, until a glomerular filtration rate (GFR of 12 mL/min. A renal biopsy demonstrated glomerular deposition of immunoglobulin k light chain. The presence of a small population of monoclonal plasmacytes producing an only light k monoclonal component was demonstrated and Bortezomib and Dexamethasone (BD was provided as initial therapy. After seven courses of therapy, renal function improved without dialysis requirements up to a GFR 31 mL/min. Under hematological complete response (HCR the patient underwent high dose of melphalan (HDM and autologous peripheral blood stem cell transplant. Fifty-four months later the patient remains in HCR and the GFR has progressively improved up to 48 mL/min. This report describes a notably renal function improvement in a patient with Light Chain Deposition Disease after therapy with BD followed by HDM, which can support this treatment as a future option for these patients.

  12. High-dose interleukin 2 in patients with metastatic renal cell carcinoma with sarcomatoid features.

    Science.gov (United States)

    Achkar, Tala; Arjunan, Ananth; Wang, Hong; Saul, Melissa; Davar, Diwakar; Appleman, Leonard J; Friedland, David; Parikh, Rahul A

    2017-01-01

    High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12-20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10-15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2. Twenty one patients with mRCC with sarcomatoid features post-nephrectomy who underwent therapy with HD IL-2 were identified at the University of Pittsburgh Medical Center from 2004 to 2016. Baseline patient characteristics, HD IL-2 cycles, time to progression, and subsequent therapies were evaluated. OS and progression-free survival (PFS) in the cohort were calculated using the Kaplan-Meier method. Disease characteristics were evaluated for significance using the Fischer's exact test and Wilcoxon rank sum test. Patients were predominantly Caucasian males with a median age of 54 years. A majority, 86% of these patients, had metastatic disease at time of initial presentation, primarily with lung and lymph node involvement. The ORR and CR with HD IL-2 was 10% and 5%, respectively. Initial localized disease presentation is the only variable that was significantly associated with response to HD IL-2 (p = 0.0158). Number of HD IL-2 doses did not correlate with response with a mean of 16.5 and 15.0 total doses in responders and non-responders, respectively (p = 0.53). Median PFS with HD IL-2 was 7.9 months (95% CI, 5.0-21.3). Median OS was 30.5 months (95% CI 13.3-57.66). Within the subset of patients who had progression on IL-2, median OS was 19.4 months (95% CI, 13.3-35.3). In patients who received second-line therapy, median PFS was 7.9 months (95% CI 2.4-10.2). In

  13. Colony, hanging drop, and methylcellulose three dimensional hypoxic growth optimization of renal cell carcinoma cell lines.

    Science.gov (United States)

    Matak, Damian; Brodaczewska, Klaudia K; Lipiec, Monika; Szymanski, Łukasz; Szczylik, Cezary; Czarnecka, Anna M

    2017-08-01

    Renal cell carcinoma (RCC) is the most lethal of the common urologic malignancies, comprising 3% of all human neoplasms, and the incidence of kidney cancer is rising annually. We need new approaches to target tumor cells that are resistant to current therapies and that give rise to recurrence and treatment failure. In this study, we focused on low oxygen tension and three-dimensional (3D) cell culture incorporation to develop a new RCC growth model. We used the hanging drop and colony formation methods, which are common in 3D culture, as well as a unique methylcellulose (MC) method. For the experiments, we used human primary RCC cell lines, metastatic RCC cell lines, human kidney cancer stem cells, and human healthy epithelial cells. In the hanging drop assay, we verified the potential of various cell lines to create solid aggregates in hypoxic and normoxic conditions. With the semi-soft agar method, we also determined the ability of various cell lines to create colonies under different oxygen conditions. Different cell behavior observed in the MC method versus the hanging drop and colony formation assays suggests that these three assays may be useful to test various cell properties. However, MC seems to be a particularly valuable alternative for 3D cell culture, as its higher efficiency of aggregate formation and serum independency are of interest in different areas of cancer biology.

  14. Regulatory mechanism of ulinastatin on autophagy of macrophages and renal tubular epithelial cells

    Directory of Open Access Journals (Sweden)

    Wu Ming

    2018-04-01

    Full Text Available Kidney ischemia and hypoxia can cause renal cell apoptosis and activation of inflammatory cells, which lead to the release of inflammatory factors and ultimately result in the damage of kidney tissue and the whole body. Renal tubular cell and macrophage autophagy can reduce the production of reactive oxygen species (ROS, thereby reducing the activation of inflammatory cytoplasm and its key effector protein, caspase-1, which reduces the expression of IL-1β and IL-18 and other inflammatory factors. Ulinastatin (UTI, as a glycoprotein drug, inhibits the activity of multiple proteases and reduces myocardial damage caused by ischemia-reperfusion by upregulating autophagy. However, it can be raised by macrophage autophagy, reduce the production of ROS, and ultimately reduce the expression of inflammatory mediators, thereby reducing renal cell injury, promote renal function recovery is not clear. In this study, a series of cell experiments have shown that ulinastatin is reduced by regulating the autophagy of renal tubular epithelial cells and macrophages to reduce the production of reactive oxygen species and inflammatory factors (TNF-α, IL-1β and IL-1, and then, increase the activity of the cells under the sugar oxygen deprivation model. The simultaneous use of cellular autophagy agonists Rapamycin (RAPA and ulinastatin has a synergistic effect on the production of reactive oxygen species and the expression of inflammatory factors.

  15. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

    Science.gov (United States)

    Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

    2017-11-01

    Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

  16. Erythrocytosis caused by giant chromophobe renal cell carcinoma: a case report indicating a 9-year misdiagnosis of polycythemia vera.

    Science.gov (United States)

    Guo, Renbo; Liang, Yiran; Yan, Lei; Xu, Zhonghua; Ren, Juchao

    2017-09-06

    Erythrocytosis, a rare paraneoplastic syndrome, generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma. We report a case of a young man suffering from a giant (22-cm) mass on his left kidney. Because of a history of polycythemia vera, the patient had been treated for the condition for 9 years. Radical nephrectomy was successfully performed, and the postoperative pathologic examination confirmed a diagnosis of chromophobe renal cell carcinoma. Unexpectedly, the symptom of erythrocytosis disappeared after the surgery. Further examination and analysis were performed, and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma. Chromophobe renal cell carcinoma could cause erythrocytosis, but the clear-cut mechanism needs further research. Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

  17. An aggressive merkel cell carcinoma in a patient with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Sevda Gizlenti

    2014-12-01

    Full Text Available Merkel cell carcinoma (MCC is a rare cutaneous tumor arising from neuroendocrine cells and Merkel cells. Early diagnosis and treatment is important because of its aggressive course. We here report a 61 years old man with chronic renal failure, 3x5 cm mass on his right leg and inguinal-paraaortic lymph node metastases and resulting in death. MCC in the literature of the AIDS disease, organ transplantation, immunosuppressive therapy areas, and additional malignancies (multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and melanoma have been reported in patients with increased incidence. Up to date a patient with renal transplantation and Merkel cell carcinoma have been reported in the literature, Merkel cell carcinoma with chronic renal failure have not been reported.

  18. Lymph node non-Hodgkin's lymphoma incidentally discovered during a nephrectomy for renal cell carcinoma.

    Science.gov (United States)

    Fernandez-Pello, Sergio; Rodriguez Villamil, Luis; Gonzalez Rodriguez, Ivan; Venta, Victoria; Cuervo, Javier; Menéndez, Carmen Luz

    2013-06-16

    We report the case of a left laparoscopic nephroureterectomy with the incidental discovery of a non-Hodgkin's lymphoma in one of the lymph nodes of the renal hilum. A laparoscopic nephroureterectomy was decided on for a 64-year-old man. Renal cell carcinoma in the kidney and one lymph node of the renal hilum with non-Hodgkin's lymphoma was found. Chemotherapy was not started for the lymphoma discovery. There are no signs of relapse after two years of follow up. Coexistence in the same patient is an extremely rare condition. We review the literature about this issue to clarify this association.

  19. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America.

    Science.gov (United States)

    Stadler, Walter M; Figlin, Robert A; McDermott, David F; Dutcher, Janice P; Knox, Jennifer J; Miller, Wilson H; Hainsworth, John D; Henderson, Charles A; George, Jeffrey R; Hajdenberg, Julio; Kindwall-Keller, Tamila L; Ernstoff, Marc S; Drabkin, Harry A; Curti, Brendan D; Chu, Luis; Ryan, Christopher W; Hotte, Sebastien J; Xia, Chenghua; Cupit, Lisa; Bukowski, Ronald M

    2010-03-01

    The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. The most common grade > or =2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

  20. Molecular features of renal cell carcinoma: early diagnostics and perspectives for therapy

    Directory of Open Access Journals (Sweden)

    O. V. Kovaleva

    2014-01-01

    Full Text Available Kidney cancer (renal cell carcinoma is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remains to be hard to diagnose and to treat, since the symptoms can be detected on advanced stages of the disease. In Russia 75.4 % of renal cell carcinoma cases detected at the stage of local and locally advanced disease. Though there are various target drugs on the market aimed to treat this disease, the results of renal cell carcinoma treatment did not reach any substantial success. Most of existing target drugs for kidney cancer treatment include inhibitors of a single signalingpathway regulated by VHL1, which expression is lost in the vast majority of renal-cell carcinomas. Till now existing drugs did not reach sufficient efficacy. Therefore, it is highly important to search for new signaling pathways, regulating such cellular processes as proliferation, migration and apoptosis. Further, prognostic markers and therapy targets identified so far are not sufficient and poorly specific. Therefore identification and validation of new markers, and especially new specific targets for the treatment of kindey oncopathologies is highly important and timely task.

  1. Polymorphisms in STAT4 increase the risk of acute renal allograft rejection in the Chinese population.

    Science.gov (United States)

    Yang, H; Zhou, Q; Chen, Z M; Chen, W Q; Wang, M M; Chen, J H

    2011-05-01

    Recently, the signal transducer and activator of transcription 4 (STAT4) gene have been associated with multiple autoimmune diseases. Taking into consideration that the different autoimmune diseases may share some common pathogenetic pathways, the aim of the present study was to evaluate the role of STAT4 rs7574865 polymorphism on acute allograft rejection. The present case-control study included 453 renal allograft recipients and 378 sex matched healthy controls. Genotyping was performed using a PCR based discrimination assay for the rs7574865 STAT4 SNP. No evidence of association was found between health controls and renal transplant recipients for the G/T or T/T genotype and wild type G/G. (p=0.431, two-tailed χ(2); OR=0.894, 95% CI=0.677-1.181). But among the transplant recipients, the G/T or T/T genotype was more common in transplant rejectors (acute allograft rejection) than nonrejectors who had mostly wild-type G/G genotype (p=0.003, two-tailed χ(2); OR=0.542, 95% CI=0.361-0.815). We also found a trend that the frequency of G/T or T/T genotype was also relatively more in the acute cellular mediated rejection than antibody mediated ones (p=0.049, two-tailed χ(2); OR=0.466, 95% CI=0.216-1.003). Thus, our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for acute renal allograft rejection in the Chinese population. Copyright © 2011. Published by Elsevier B.V.

  2. [Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].

    Science.gov (United States)

    Li, Peng; Han, Qi; Tang, Ming; Zhang, Keqin

    2017-03-01

    Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.

  3. Detection of Thyroid Metastasis pf Renal Transitional Cell Carcinoma Using FDG PET/CT

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    Kim, Yong Il; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. Bundang Hospital, Seoul (Korea, Republic of); Lee, Jong Jin [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of); Paik, Jin Ho [Seoul National Univ. Bundang Hospital, Seoul (Korea, Republic of)

    2011-06-15

    A 69 year old man who was diagnosed with renal transitional cell carcinoma (TCC) underwent F 18 fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) for detecting recurrence after chemotherapy. FDG PET/CT revealed multiple new hypermetabolic lesions in many places, including the right thyroid gland. Biopsy of the thyroid lesion was performed,and a diagnosis of metastatic TCC was made. We could detect thyroid metastasis of renal TCC by FDG PET/CT.

  4. Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

    2018-02-23

    Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

    Science.gov (United States)

    Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

    2013-01-01

    Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

  6. Imaging features of renal complications after crizotinib treatment for non–small-cell lung cancer: a case report

    Directory of Open Access Journals (Sweden)

    Wan Ying Chan, MBBS

    2016-09-01

    Full Text Available Crizotinib has been approved for the treatment of advanced ALK-positive non–small cell lung cancer. Its use is associated with the development of complex renal cysts. However, there is limited literature regarding imaging features of renal cystic disease during crizotinib therapy and its complications or progression. Here, we describe a case of a patient with ALK-positive advanced non–small cell lung cancer who developed complex renal cyst during crizotinib treatment. The renal cyst is complicated by infection and abscess formation. Subsequent renal biopsy, antibiotics treatment, and open drainage of loculated renal abscess showed no malignant cells and contributed to the diagnosis. The imaging features should be recognized as renal cystic disease of crizotinib treatment and not to be mistaken as new metastasis and disease progression.

  7. Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro

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    Morizane, Ryuji [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Monkawa, Toshiaki, E-mail: monkawa@sc.itc.keio.ac.jp [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Itoh, Hiroshi [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan)

    2009-12-25

    Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells.

  8. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

    Science.gov (United States)

    Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

  9. Preparation of positional renal slices for study of cell-specific toxicity.

    Science.gov (United States)

    Ruegg, C E; Gandolfi, A J; Nagle, R B; Krumdieck, C L; Brendel, K

    1987-04-01

    To reduce structural complexity, rabbit kidneys were sliced perpendicular to their cortical-papillary axis to isolate four distinct cell groupings. This positional orientation allows identification of each renal cell type based on its location within the slice. A mechanical slicer was used to make several precision-cut slices rapidly from an oriented cylindrical core of renal tissue, with minimal tissue trauma. Slices were then submerged under a gently circulating oxygenated media in a fritted glass support system that maintains viability (intracellular K+/DNA ratio) and structural integrity (histology) for at least 30 h. A high dose of mercuric chloride (10(-3) M) was used to demonstrate the structural and biochemical changes of intoxicated slices. This method provides a controlled subchronic in vitro system for the study of the individual cell types involved in cell-specific renal toxicities and may also be a useful tool for addressing other pharmacological and physiological research questions.

  10. International variations and trends in renal cell carcinoma incidence and mortality.

    Science.gov (United States)

    Znaor, Ariana; Lortet-Tieulent, Joannie; Laversanne, Mathieu; Jemal, Ahmedin; Bray, Freddie

    2015-03-01

    Renal cell carcinoma (RCC) incidence rates are higher in developed countries, where up to half of the cases are discovered incidentally. Declining mortality trends have been reported in highly developed countries since the 1990s. To compare and interpret geographic variations and trends in the incidence and mortality of RCC worldwide in the context of controlling the future disease burden. We used data from GLOBOCAN, the Cancer Incidence in Five Continents series, and the World Health Organisation mortality database to compare incidence and mortality rates in more than 40 countries worldwide. We analysed incidence and mortality trends in the last 10 yr using joinpoint analyses of the age-standardised rates (ASRs). RCC incidence in men varied in ASRs (World standard population) from approximately 1/100,000 in African countries to >15/100,000 in several Northern and Eastern European countries and among US blacks. Similar patterns were observed for women, although incidence rates were commonly half of those for men. Incidence rates are increasing in most countries, most prominently in Latin America. Although recent mortality trends are stable in many countries, significant declines were observed in Western and Northern Europe, the USA, and Australia. Southern European men appear to have the least favourable RCC mortality trends. Although RCC incidence is still increasing in most countries, stabilisation of mortality trends has been achieved in many highly developed countries. There are marked absolute differences and opposing RCC mortality trends in countries categorised as areas of higher versus lower human development, and these gaps appear to be widening. Renal cell cancer is becoming more commonly diagnosed worldwide in both men and women. Mortality is decreasing in the most developed settings, but not in low- and middle-income countries, where access to and the availability of optimal therapies are likely to be limited. Copyright © 2014 European Association of

  11. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

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    Raissouni Soundouss

    2012-08-01

    Full Text Available Abstract Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  12. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma.

    Science.gov (United States)

    Raissouni, Soundouss; Raissouni, Ferdaous; Rais, Ghizlane; Aitelhaj, Meryem; Lkhoyaali, Siham; Latib, Rachida; Mohtaram, Amina; Rais, Fadoua; Mrabti, Hind; Kabbaj, Nawal; Amrani, Naima; Errihani, Hassan

    2012-08-09

    Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  13. Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.

    Science.gov (United States)

    Narula, Shifa; Tandon, Simran; Singh, Shrawan Kumar; Tandon, Chanderdeep

    2016-11-01

    Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury. The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis. Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury. The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Unusual Upper Gastrointestinal Bleeding due to Late Metastasis from Renal Cell Carcinoma: A Case Report

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    Wen-Tsan Chang

    2004-03-01

    Full Text Available A case of recurrent massive upper gastrointestinal bleeding originating from metastatic renal cell carcinoma is reported. A 63-year-old woman underwent right nephrectomy 9 years previously and experienced no recurrence during follow-up. A gradually enlarging ulcerative tumor over the bulb of the duodenum and four subsequent episodes of massive bleeding from this tumor occurred between June 2001 and March 2002. The patient underwent surgery in April 2002 for intractable bleeding from the tumor. Renal cell carcinoma metastasis to the duodenum was confirmed from the surgical specimen. Upper gastrointestinal bleeding due to malignancy is very rare and the duodenum is the least frequently involved site. Furthermore, a solitary late renal cell carcinoma metastasis 9 years after a nephrectomy is extremely uncommon. This case suggests that life-long follow-up of renal cell carcinoma patients is necessary, owing to unpredictable behavior and the possibility of long disease-free intervals. In nephrectomized patients suffering from gastrointestinal bleeding, complete evaluation, especially endoscopic examination, is indicated. The possibility of late recurrent renal cell carcinoma metastasis to the gastrointestinal tract should be kept in mind, although it is rare. If the patient is fit for surgery, metastatectomy is the first choice of treatment.

  15. Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

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    Geurt Stokman

    Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

  16. Surgery on spinal epidural metastases (SEM) in renal cell carcinoma: a plea for a new paradigm.

    Science.gov (United States)

    Bakker, Nicolaas A; Coppes, Maarten H; Vergeer, Rob A; Kuijlen, Jos M A; Groen, Rob J M

    2014-09-01

    Prediction models for outcome of decompressive surgical resection of spinal epidural metastases (SEM) have in common that they have been developed for all types of SEM, irrespective of the type of primary tumor. It is our experience in clinical practice, however, that these models often fail to accurately predict outcome in the individual patient. To investigate whether decision making could be optimized by applying tumor-specific prediction models. For the proof of concept, we analyzed patients with SEM from renal cell carcinoma that we have operated on. Retrospective chart analysis 2006 to 2012. Twenty-one consecutive patients with symptomatic SEM of renal cell carcinoma. Predictive factors for survival. Next to established predictive factors for survival, we analyzed the predictive value of the Motzer criteria in these patients. The Motzer criteria comprise a specific and validated risk model for survival in patients with renal cell carcinoma. After multivariable analysis, only Motzer intermediate (hazard ratio [HR] 17.4, 95% confidence interval [CI] 1.82-166, p=.01) and high risk (HR 39.3, 95% CI 3.10-499, p=.005) turned out to be significantly associated with survival in patients with renal cell carcinoma that we have operated on. In this study, we have demonstrated that decision making could have been optimized by implementing the Motzer criteria next to established prediction models. We, therefore, suggest that in future, in patients with SEM from renal cell carcinoma, the Motzer criteria are also taken into account. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

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    Clara E. Jäkel

    2012-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.

  18. Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia.

    Science.gov (United States)

    Patschan, D; Michurina, T; Shi, H K; Dolff, S; Brodsky, S V; Vasilieva, T; Cohen-Gould, L; Winaver, J; Chander, P N; Enikolopov, G; Goligorsky, M S

    2007-04-01

    Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

  19. Expression of minichromosome maintenance genes in renal cell carcinoma

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    Zhong HB

    2017-11-01

    Full Text Available Hongbin Zhong,1,* Bin Chen,1,* Henrique Neves,2 Jinchun Xing,1 Youxin Ye,1 Ying Lin,1 Guohong Zhuang,3 Shu-Dong Zhang,4 Jiyi Huang,1,5 Hang Fai Kwok2 1Xiang’an Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Faculty of Health Sciences, University of Macau, Taipa, Macau SAR; 3Medical College of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry, UK; 5The First Clinical School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China *These authors contributed equally to this work Abstract: Minichromosome maintenance (MCM proteins play an essential role in DNA replication. They have been shown to be overexpressed in various types of cancer. However, the role of this family in renal cell carcinoma (RCC is widely unknown. In this study, we have identified a number of RCC datasets in the Gene Expression Omnibus database and also investigated the correlation between the expression levels of MCM genes and clinicopathological parameters. We found that the expression levels of MCM genes are positively correlated with one another. Expression levels of MCM2, MCM5, MCM6, and MCM7, but not of MCM3 and MCM4, were higher in RCC compared to paired adjacent normal tissue. Only the expression level of MCM4, but not of other MCMs, was positively correlated with tumor grade. In addition, a high-level expression of MCM2 in either primary tumor or metastases of RCC predicted a shorter disease-free survival time, while a high-level expression of MCM4 or MCM6 in primary tumor was also associated with poorer disease-free survival. Interestingly, we also demonstrated that patients with their primary RCC overexpressing 2 or more MCM genes had a shorter disease-free survival time, while those with RCC metastases overexpressing 3 or more MCM genes had a shorter

  20. Neoadjuvant targeted therapy in patients with renal cell carcinoma

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    B. Ya. Alekseev

    2015-01-01

    Full Text Available Cytoreductive nephrectomy as an independent option in patients with metastatic renal cell carcinoma (mRCC cannot be considered as the only effective method, with rare exception, of a few patients with solitary metastases. Cytoreductive nephrectomy is now part of a multimodal approach encompassing surgical treatment and systemic drug therapy. Many retrospective and two prospective studies have demonstrated that it is expedient to perform cytoreductive nephrectomy. Immunotherapy should not be used as preoperatively in the era of cytokine therapy for mRCC due to that fact that it has no impact on primary tumor. In the current targeted therapy era, many investigators have concentrated attentionon the role of neoadjuvant targeted therapy for the treatment of patients with both localized and locally advanced mRCC. The potential benefits of neoadjuvant therapy for localized and locally advanced RCC include to make surgery easier and to increase the possibility of organsparing treatment, by decreasing the stage of primary tumor and the size of tumors. The possible potential advantages of neoadjuvant targeted therapy in patients with mRCC include prompt initiation of necessary systemic therapy; identification of patients with primary refractory tumors; and a preoperative reduction in the stage of primary tumor. Numerous retrospective and some prospective phase II studies have shown that neoadjuvant targeted therapy in patients with localized and locally advanced RCC is possible and tolerable and surgical treatment after neoadjuvant targeted therapy is safe and executable with a low incidence of complications. If neoadjuvant therapy is to be performed, it should be done within 2–4 months before surgery. Sorafenib and sunitinib are now most tested and suitable for neoadjuvant targeted therapy. Sorafenib is a more preferred drug due to its shorter half-life and accordingly to the possibility of discontinuing the drug immediately prior to

  1. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    NARCIS (Netherlands)

    Ricketts, Christopher J.; De Cubas, Aguirre A.; Fan, Huihui; Smith, Christof C.; Lang, Martin; Reznik, Ed; Bowlby, Reanne; Gibb, Ewan A.; Akbani, Rehan; Beroukhim, Rameen; Bottaro, Donald P.; Choueiri, Toni K.; Gibbs, Richard A.; Godwin, Andrew K.; Haake, Scott; Hakimi, A. Ari; Henske, Elizabeth P.; Hsieh, James J.; Ho, Thai H.; Kanchi, Rupa S.; Krishnan, Bhavani; Kwaitkowski, David J.; Lui, Wembin; Merino, Maria J.; Mills, Gordon B.; Myers, Jerome; Nickerson, Michael L.; Reuter, Victor E.; Schmidt, Laura S.; Shelley, Carl Simon; Shen, Hui; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Vincent, Benjamin G.; Vocke, Cathy D.; Wheeler, David A.; Yang, Lixing; Kim, William T.; Robertson, A. Gordon; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Gonzalez, Ana Maria Angulo; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, onathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Pinero, Edna M.Mora; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Spellman, Paul T.; Rathmell, W. Kimryn; Linehan, W. Marston

    2018-01-01

    Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC,

  2. Interactions of virulent and avirulent leptospires with primary cultures of renal epithelial cells

    DEFF Research Database (Denmark)

    Ballard, S A; Williamson, M; Adler, B

    1986-01-01

    A primary culture system for the cells of mouse renal-tubular epithelium was established and used to observe the adhesion of leptospires. Virulent strains of serovars copenhageni and ballum attached themselves to epithelial cells within 3 h of infection whereas an avirulent variant of serovar cop...

  3. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

    2015-01-01

    stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  4. Not all renal stem cell niches are the same: anatomy of an evolution

    Directory of Open Access Journals (Sweden)

    Clara Gerosa

    2016-08-01

    Full Text Available The renal stem cell niche represents the most important structure of the developing kidney, responsible for nephrogenesis. Recently, some Authors have reported, at ultrastructural level, a previously unknown complexity of the architecture of renal stem cell niche in experimental models. This study was aimed at studying, at histological level, the anatomy of renal stem cell niches in the human fetal kidney. To this end, ten fetal kidneys, whose gestational ages ranged from 11 up to 24 weeks, were studied. H&E-stained sections were observed at high power. The study of the anatomy of renal stem cell niches in the human kidney revealed a previously unreported complexity: some niches appeared as a roundish arrangement of mesenchymal cells; others showed the initial phases of induction by ureteric buds; in other niches the process of mesenchymal epithelial transition was more evident; finally, in other stem cell niches the first signs of nephron origin were detectable. These findings suggest the existence of niches with different anatomy in the same kidney, indicating different stages of evolution even in adjacent niches. All stem cell niches were in strict contact with the capsular cells, suggesting a major role of the renal capsule in nephrogenesis. Finally, our study confirms the existence of a strict contact between the bud tip cells and the surrounding mesenchyme in the human developing kidney, giving a morphological support to the theory of intercellular channels allowing the passage of transcription factors from the epithelial to the mesenchymal stem/progenitors cells.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  5. Cell-metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

    International Nuclear Information System (INIS)

    Milgram, S.; Carriere, M.; Thiebault, C.; Berger, P.; Khodja, H.; Gouget, B.

    2007-01-01

    Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se IV and Cu as the most toxic and Ni, Se VI , Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS

  6. Cell-metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Milgram, S. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Carriere, M. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Thiebault, C. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Berger, P. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Khodja, H. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gouget, B. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)]. E-mail: barbara.gouget@cea.fr

    2007-07-15

    Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se{sup IV} and Cu as the most toxic and Ni, Se{sup VI}, Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS.

  7. T Cells and Pathogenesis of Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

    OpenAIRE

    Francis A. Ennis; Masanori Terajima

    2011-01-01

    We previously hypothesized that increased capillary permeability observed in both hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) may be caused by hantavirus-specific cytotoxic T cells attacking endothelial cells presenting viral antigens on their surface based on clinical observations and in vitro experiments. In HCPS, hantavirus-specific T cell responses positively correlated with disease severity. In HFRS, in one report, contrary to HCPS, T cell ...

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

    African Journals Online (AJOL)

    It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs) and mesenchymal stem cells (MSCs). Characterization of HSCs ...

  9. Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data

    International Nuclear Information System (INIS)

    Lenburg, Marc E; Liou, Louis S; Gerry, Norman P; Frampton, Garrett M; Cohen, Herbert T; Christman, Michael F

    2003-01-01

    Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated. To better understand this lack of agreement we profiled renal cell tumor gene expression using genome-wide microarrays (45,000 probe sets) and compare our analysis to previous microarray studies. We hybridized total RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays. We removed samples with technical defects and removed probesets that failed to exhibit sequence-specific hybridization in any of the samples. We detected differential gene expression in the resulting dataset with parametric methods and identified keywords that are overrepresented in the differentially expressed genes with the Fisher-exact test. We identify 1,234 genes that are more than three-fold changed in renal tumors by t-test, 800 of which have not been previously reported to be altered in renal cell tumors. Of the only 37 genes that have been identified as being differentially expressed in three or more of five previous microarray studies of renal tumor gene expression, our analysis finds 33 of these genes (89%). A key to the sensitivity and power of our analysis is filtering out defective samples and genes that are not reliably detected. The widespread use of sample-wise voting schemes for detecting differential expression that do not control for false positives likely account for the poor overlap among previous studies. Among the many genes we identified using parametric methods that were not previously reported as being differentially expressed in renal cell tumors are several oncogenes and tumor suppressor genes that likely play important roles in renal cell

  10. A generic RNA-pulsed dendritic cell vaccine strategy for renal cell carcinoma

    Science.gov (United States)

    Geiger, Christiane; Regn, Sybille; Weinzierl, Andreas; Noessner, Elfriede; Schendel, Dolores J

    2005-01-01

    We present a generic dendritic cell (DC) vaccine strategy for patients with renal cell carcinoma (RCC) based on the use of RNA as a source of multiplex tumor-associated antigens (TAAs). Instead of preparing RNA from tumor tissue of each individual RCC patient, we propose to substitute RNA prepared from a well characterized highly immunogenic RCC cell line (RCC-26 tumor cells) as a generic source of TAAs for loading of DCs. We demonstrate here that efficient RNA transfer can be achieved using lipofection of immature DCs, which are subsequently matured with a cytokine cocktail to express high levels of MHC and costimulatory molecules as well as the chemokine receptor CCR7. Neither RNA itself nor the lipid component impacted on the phenotype or the cytokine secretion of mature DCs. Following RNA loading, DCs derived from HLA-A2-positive donors were able to activate effector-memory cytotoxic T lymphocytes (CTLs) specific for a TAA ligand expressed by the RCC-26 cell line. CTL responses to RNA-loaded DCs reached levels comparable to those stimulated directly by the RCC-26 tumor cells. Furthermore, DCs expressing tumor cell RNA primed naïve T cells, yielding T cell lines with cytotoxicity and cytokine secretion after contact with RCC tumor cells. RCC-26 cell lines are available as good manufacturing practice (GMP)-certified reagents enabling this source of RNA to be easily standardized and adapted for clinical testing. In addition, well defined immune monitoring tools, including the use of RNA expressing B cell lines, are available. Thus, this DC vaccine strategy can be directly compared with an ongoing gene therapy trial using genetically-engineered variants of the RCC-26 cell line as vaccines for RCC patients with metastatic disease. PMID:16045799

  11. A generic RNA-pulsed dendritic cell vaccine strategy for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Noessner Elfriede

    2005-07-01

    Full Text Available Abstract We present a generic dendritic cell (DC vaccine strategy for patients with renal cell carcinoma (RCC based on the use of RNA as a source of multiplex tumor-associated antigens (TAAs. Instead of preparing RNA from tumor tissue of each individual RCC patient, we propose to substitute RNA prepared from a well characterized highly immunogenic RCC cell line (RCC-26 tumor cells as a generic source of TAAs for loading of DCs. We demonstrate here that efficient RNA transfer can be achieved using lipofection of immature DCs, which are subsequently matured with a cytokine cocktail to express high levels of MHC and costimulatory molecules as well as the chemokine receptor CCR7. Neither RNA itself nor the lipid component impacted on the phenotype or the cytokine secretion of mature DCs. Following RNA loading, DCs derived from HLA-A2-positive donors were able to activate effector-memory cytotoxic T lymphocytes (CTLs specific for a TAA ligand expressed by the RCC-26 cell line. CTL responses to RNA-loaded DCs reached levels comparable to those stimulated directly by the RCC-26 tumor cells. Furthermore, DCs expressing tumor cell RNA primed naïve T cells, yielding T cell lines with cytotoxicity and cytokine secretion after contact with RCC tumor cells. RCC-26 cell lines are available as good manufacturing practice (GMP-certified reagents enabling this source of RNA to be easily standardized and adapted for clinical testing. In addition, well defined immune monitoring tools, including the use of RNA expressing B cell lines, are available. Thus, this DC vaccine strategy can be directly compared with an ongoing gene therapy trial using genetically-engineered variants of the RCC-26 cell line as vaccines for RCC patients with metastatic disease.

  12. 'Known unknowns - examining the burden of neurocognitive impairment in the end-stage renal failure population'.

    Science.gov (United States)

    Wilson, Scott; Dhar, Arup; Tregaskis, Peter; Lambert, Gavin; Barton, David; Walker, Rowan

    2018-01-18

    The burden of neurocognitive impairment (NCI) in patients receiving maintenance dialysis represents a spectrum of deficits across multiple cognitive domains which are associated with hospitalisation, reduced quality-of-life, mortality and forced decision-making around dialysis withdrawal. Point prevalence data suggests that dialysis patients manifest NCI at rates 3-5 fold higher than the general population with executive function the most commonly affected cognitive domain. The unique physiology of the renal failure state and maintenance dialysis appears to drive an excess of vascular dementia subtype compared to the general population where classical Alzheimer's disease predominates. Despite the absence of evidence based cost-effective therapies for NCI, detecting it in this population creates opportunity to proactively personalise care through education, supported decision making and targeted communication strategies to cover specific areas of deficit and help define goals of care. This review discusses NCI in the dialysis setting, including developments in the definition of neurocognitive impairment, dialysis-specific epidemiology across modalities, screening strategies and opportunities for dialysis providers in this space. This article is protected by copyright. All rights reserved.

  13. IgG4-related tubulointerstitial nephritis with plasma cell-rich renal arteritis.

    Science.gov (United States)

    Sharma, Shree G; Vlase, Horia L; D'Agati, Vivette D

    2013-04-01

    Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis is a newly recognized clinicopathologic entity that may occur as an isolated renal lesion or as part of a multisystem disorder. It is characterized by plasma cell-rich interstitial nephritis with abundant IgG4-positive plasma cells and IgG-dominant tubulointerstitial immune deposits. We report the first case of IgG4-related tubulointerstitial nephritis with multifocal plasma cell-rich renal arteritis presenting as acute kidney injury in a 72-year-old man. Seven weeks of prednisone therapy led to nearly complete recovery of kidney function. This case enlarges the morphologic spectrum of this disorder and emphasizes the need to distinguish it from other causes of renal vasculitis. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  14. Direct Reprogramming of Human Bone Marrow Stromal Cells into Functional Renal Cells Using Cell-free Extracts

    Directory of Open Access Journals (Sweden)

    Evangelia Papadimou

    2015-04-01

    Full Text Available The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs, also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes—formation of “domes” and tubule-like structures—and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy.

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

    Directory of Open Access Journals (Sweden)

    Thomas Buus Jensen

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

  16. The association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium in China.

    Science.gov (United States)

    Chen, Xiao; Dai, Yan; Wang, Zhongqiu; Zhu, Guoying; Ding, Xiaoqiang; Jin, Taiyi

    2018-01-01

    Cadmium exposure can cause renal tubular dysfunction. Recent studies show that vitamin D can play multiple roles in the body. However, the association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium has not been clarified. We performed study to assess the effects of cadmium on serum 25(OH) D levels and the association between serum 25(OH) D levels and renal tubular dysfunction in a population environmentally exposed to cadmium. A total of 133 subjects living in control area and two cadmium polluted areas were included in the present study. Cadmium in urine (UCd) and blood (BCd), urinary β2Microglobulin (UBMG), urinary retinol binding protein (URBP) and serum 25 (OH) D were determined. Logistic regression was used to estimate the association between 25 (OH) D and prevalence of renal tubular dysfunction. No significant differences were observed in serum 25(OH) D levels among the four quartile of UCd and BCd after adjusting with cofounders. After adjusted with the confounders, the odds ratio (OR) of subjects with 25(OH) D ≥ 40 ng/ml were 0.20 (95%CI: 0.1-0.8) if UBMG was chosen as indicators of renal dysfunction and 0.28 (95%CI: 0.1-1.1) if URBP was chosen as indicators of renal dysfunction, compared with those with 25(OH) D < 30 ng/ml, respectively. Similar results were observed in those subjects living in cadmium polluted areas or with high level of UCd or BCd. Our data indicated that cadmium exposure did not affect serum 25(OH) D level and high 25 (OH) D levels were associated with a decreased risk of renal tubular dysfunction induced by cadmium.

  17. Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

    Science.gov (United States)

    Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Vuistiner, Philippe; Guessous, Idris; Ehret, Georg; Alwan, Heba; Youhanna, Sonia; Paccaud, Fred; Mohaupt, Markus; Péchère-Bertschi, Antoinette; Vogt, Bruno; Burnier, Michel; Martin, Pierre-Yves; Devuyst, Olivier; Bochud, Murielle

    2015-06-01

    Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts. Copyright © 2015 by the American Society of Nephrology.

  18. Associations of mitochondrial haplogroups and mitochondrial DNA copy numbers with end-stage renal disease in a Han population.

    Science.gov (United States)

    Zhang, Yuheng; Zhao, Ying; Wen, Shuzhen; Yan, Rengna; Yang, Qinglan; Chen, Huimei

    2017-09-01

    Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and variations have been suggested to be involved in pathogenesis of complex diseases. The present study sought to elucidate mitochondrial haplogroups and mtDNA copy number in end-stage renal disease (ESRD) in a Han population. First, the mitochondrial haplogroups of 37 ESRD patients were clustered into several haplogroups, and haplogroup A & D were taken as the candidate risk haplogroups for ESRD. Second, the frequencies of A and D were assessed in 344 ESRD patients and 438 healthy controls, respectively. Haplogroup D was found to be risk maker for ESRD in young subjects (numbers were evaluated with quantitative-PCR. The ESRD patients exhibited greater cell-free mtDNA contents than the healthy controls but less intracellular mtDNA. Haplogroup D exhibited a further increase in cell-free mtDNA content and a decrease in intracellular mtDNA content among the ESRDs patients. Our findings suggest that mtNDA haplogroup D may contributes to pathogenesis of early-onset ESRD through alterations of mtDNA copy numbers.

  19. Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cheol Lee

    2017-07-01

    Full Text Available Background Clear cell renal cell carcinoma (CCRCC is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2 has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry. Methods We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed. Results Among 254 CCRCC cases, 150 cases (59.1% showed high expression and 104 cases (40.1% showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001, smaller tumor size (p < .001, low overall stage (p = .003, longer cancer-specific survival (p = .002, and progression-free survival (p < .001 of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage. Conclusions Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

  20. Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

    Science.gov (United States)

    Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

    2017-10-01

    To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    Science.gov (United States)

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. The Expression of BTS-2 Enhances Cell Growth and Invasiveness in Renal Cell Carcinoma.

    Science.gov (United States)

    Pham, Quoc Thang; Oue, Naohide; Yamamoto, Yuji; Shigematsu, Yoshinori; Sekino, Yohei; Sakamoto, Naoya; Sentani, Kazuhiro; Uraoka, Naohiro; Tiwari, Mamata; Yasui, Wataru

    2017-06-01

    Renal cell carcinoma (RCC) is one of the most common types of cancer in developed countries. Bone marrow stromal cell antigen 2 (BST2) gene, which encodes BST2 transmembrane glycoprotein, is overexpressed in several cancer types. In the present study, we analyzed the expression and function of BST2 in RCC. BST2 expression was analyzed by immunohistochemistry in 123 RCC cases. RNA interference was used to inhibit BST2 expression in a RCC cell line. Immunohistochemical analysis showed that 32% of the 123 RCC cases were positive for BST2. BST2 expression was positively associated with tumour stage. Furthermore, BST2 expression was an independent predictor of survival in patients with RCC. BST2 siRNA-transfected Caki-1 cells displayed significantly reduced cell growth and invasive activity relative to negative control siRNA-transfected cells. These results suggest that BST2 plays an important role in the progression of RCC. Because BST2 is expressed on the cell membrane, BST2 is a good therapeutic target for RCC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Skeletal metastasis in renal cell carcinoma: A review

    Directory of Open Access Journals (Sweden)

    Masood Umer

    2018-03-01

    Conclusion: Incidence of metastatic renal carcinoma is increasing. Overall prognosis of patient with advanced RCC is poor, emphasizing the importance of early detection and prompt treatment of primary lesion in its early stage. Advancement in targeted therapy in recent decades had made some improvement in treatment of SREs and has helped in improving patent's quality of life but still we are in need of further improvement in treatment modalities to cure disease thereby decreasing morbidity and mortality.

  4. Bilateral renal cell carcinoma in a horseshoe kidney: preoperative assessment with MRI and digital subtraction angiography

    International Nuclear Information System (INIS)

    Schubert, R.A.; Soeldner, J.; Kaiser, W.A.; Steiner, T.; Schubert, J.

    1998-01-01

    Renal cell carcinoma in a horseshoe kidney is an unusual entity. To our knowledge, only 123 cases have been published to date. We report the first bilateral case of two clear-cell carcinomas in an asymmetrically fused kidney. Optimum preservation of renal function after radical tumor removal requires accurate preoperative imaging. Since the vascular supply in fusion anomalies is extremely variable, angiography is mandatory. Magnetic resonance imaging was most suitable to predict the tumor extent and localization, because it simultaneously gave the most comprehensive anatomical overview of the malformation. (orig.)

  5. Temsirolimus Is Highly Effective as Third-Line Treatment in Chromophobe Renal Cell Cancer

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    Dimitrios Zardavas

    2011-01-01

    Full Text Available We report unexpectedly high efficacy of temsirolimus as third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. After failure of two sequentially administered tyrosine kinase inhibitors, treatment with temsirolimus resulted in a prolonged partial remission of 14 months, and the response is still continuing. Up to now, no data from randomized clinical studies have been published addressing the question of efficacy of temsirolimus as third-line treatment after failure of tyrosine kinase inhibitors. The case presented here implies that temsirolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.

  6. Renal cell carcinoma: new insights and challenges for a clinician scientist.

    Science.gov (United States)

    Shingarev, Roman; Jaimes, Edgar A

    2017-08-01

    There is a growing recognition of the complex interplay between renal cell cancer (RCC), kidney function, mechanical reduction of nephron mass, and systemic agents targeting the cancer. Earlier detection of RCC and rising life expectancy of cancer survivors places a greater emphasis on preservation of renal function after cancer resection and during systemic therapy. Unique adverse effects associated with RCC drugs not only help reveal cancer pathophysiology but also expand our knowledge of normal cell signaling and metabolism. In this review, we outline our current understanding of RCC biology and treatment, their bidirectional relationship with kidney function, and unmet research needs in this field. Copyright © 2017 the American Physiological Society.

  7. Ischiogluteal bursitis mimicking soft-tissue metastasis from a renal cell carcinoma

    International Nuclear Information System (INIS)

    Voelk, M.; Gmeinwieser, J.; Manke, C.; Strotzer, M.; Hanika, H.

    1998-01-01

    We report a case of ischiogluteal bursitis mimicking a soft-tissue metastasis from a renal cell carcinoma. A 66-year-old woman suffered from pain over the left buttock 6 months after she was operated on for renal cell carcinoma of the left kidney. CT of the abdomen and pelvis revealed a tumor-like lesion adjacent to the left os ischii, which was suspected to be a soft-tissue metastasis. Percutaneous biopsy revealed no evidence of malignancy, but the histopathological diagnosis of chronic bursitis. (orig.)

  8. Ischiogluteal bursitis mimicking soft-tissue metastasis from a renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Voelk, M.; Gmeinwieser, J.; Manke, C.; Strotzer, M. [Department of Radiology, University Hospital, Regensburg (Germany); Hanika, H. [Department of Urology, St. Josef Hospital, Regensburg (Germany)

    1998-09-01

    We report a case of ischiogluteal bursitis mimicking a soft-tissue metastasis from a renal cell carcinoma. A 66-year-old woman suffered from pain over the left buttock 6 months after she was operated on for renal cell carcinoma of the left kidney. CT of the abdomen and pelvis revealed a tumor-like lesion adjacent to the left os ischii, which was suspected to be a soft-tissue metastasis. Percutaneous biopsy revealed no evidence of malignancy, but the histopathological diagnosis of chronic bursitis. (orig.) With 2 figs., 8 refs.

  9. Reactive Hypertrophy of an Accessory Spleen Mimicking Tumour Recurrence of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Christin Tjaden

    2011-01-01

    Full Text Available De novo occurrence of an accessory spleen after splenectomy is worth noting for two reasons. First, it is known that splenectomy can cause reactive hypertrophy of initially inactive and macroscopically invisible splenic tissue. Second, it can mimic tumour recurrence in situations in which splenectomy has been performed for oncological reasons. This might cause difficulties in differential diagnosis and the clinical decision for reoperation. We report the case of a patient with suspected recurrence of renal cell carcinoma after total pancreatectomy and splenectomy for metastatic renal cell carcinoma, which finally revealed an accessory spleen as the morphological correlate of the newly diagnosed mass in the left retroperitoneum.

  10. Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

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    J. P. Barras

    1996-01-01

    Full Text Available A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indication for pancreatic resection because of pancreatic metastasis.

  11. A Case of Squamous Cell Carcinoma of the Renal Pelvis in association with Schistosoma hematobium

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    Muhammad A. A. Khan

    2012-01-01

    Full Text Available A 72-year-old man presented with painless frank haematuria. Investigations included intravenous urogram and abdominal/pelvic CT which revealed a marked focal thickening of the wall of the inferior aspect of the left renal pelvis extending into the lower pole calyx and into the pelviureteric junction resulting in left hydronephrosis. Urine cytology demonstrated clusters of malignant keratinised squamous cells and schistosome ova. He underwent left laparoscopic radical nephroureterectomy and histology revealed moderately differentiated keratinising squamous cell carcinoma in the renal pelvis.

  12. Cytological diagnosis of a rare case of cutaneous metastasis from transitional cell carcinoma, renal pelvis

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    Pragya Singh

    2017-12-01

    Full Text Available Transitional cell carcinoma (TCC arising from renal pelvis rarely gives rise to cutaneous metastasis. Due to the insufficient literature, the exact incidence is not known till date. Moreover, the diagnosis is confirmed on histopathological examination with the aid of immunohistochemistry wherever needed. We are presenting a case of a 70-year-old female with metastatic TCC from the renal pelvis to the abdominal skin, which was diagnosed on cytology alone along with the cell block preparation. We also highlight the important cytomorphological and immunohistochemical features noted, which need to be known to avoid any diagnostic delay.

  13. Osseous metastases from renal cell carcinoma: embolization and surgery for restoration of function. Work in progress

    International Nuclear Information System (INIS)

    Rowe, D.M.; Becker, G.J.; Rabe, F.E.; Holden, R.W.; Richmond, B.D.; Wass, J.L.; Sequeira, F.W.

    1984-01-01

    Five patients underwent preoperative embolization of osseous metastases from renal cell carcinoma. The group consisted of four men and one woman who ranged in age from 46 to 79 years. The lesions were located in the pubic ramus and acetabulum, proximal femur, femoral midshaft, proximal humerus, and proximal tibia. All embolizations were performed within 24 hours of surgery. The internal fixation and tumor curettage was accomplished with estimated perioperative blood loss ranging from 10 ml to 1,250 ml. All patients had significant restoration of function following surgery. The authors suggest that preoperative embolization is an important and efficacious adjunct in the management of hypervascular renal cell osseous metastases

  14. Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure.

    Science.gov (United States)

    Caldas, Heloisa Cristina; de Paula Couto, Thaís Amarante Peres; Fernandes, Ida Maria Maximina; Baptista, Maria Alice Sperto Ferreira; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Braile, Domingo Marcolino; Abbud-Filho, Mario

    2015-10-01

    The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.

  15. Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma.

    Science.gov (United States)

    Kremer, Veronika; Ligtenberg, Maarten A; Zendehdel, Rosa; Seitz, Christina; Duivenvoorden, Annet; Wennerberg, Erik; Colón, Eugenia; Scherman-Plogell, Ann-Helén; Lundqvist, Andreas

    2017-09-19

    Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2. We hypothesize that infusion of NK cells expressing high levels of the CXCR2 chemokine receptor will result in increased influx of the transferred NK cells into tumors, and improved clinical outcome in patients with cancer. Blood and tumor biopsies from 14 primary RCC patients were assessed by flow cytometry and chemokine analysis. Primary NK cells were transduced with human CXCR2 using a retroviral system. CXCR2 receptor functionality was determined by Calcium flux and NK cell migration was evaluated in transwell assays. We detected higher concentrations of CXCR2 ligands in tumors compared with plasma of RCC patients. In addition, CXCL5 levels correlated with the intratumoral infiltration of CXCR2-positive NK cells. However, tumor-infiltrating NK cells from RCC patients expressed lower CXCR2 compared with peripheral blood NK cells. Moreover, healthy donor NK cells rapidly lost their CXCR2 expression upon in vitro culture and expansion. Genetic modification of human primary NK cells to re-express CXCR2 improved their ability to specifically migrate along a chemokine gradient of recombinant CXCR2 ligands or RCC tumor supernatants compared with controls. The enhanced trafficking resulted in increased killing of target cells. In addition, while their functionality remained unchanged compared with control NK cells, CXCR2-transduced NK cells obtained increased adhesion properties and formed more conjugates with target cells. To increase the success of NK

  16. Opposite prognostic roles of HIF1β and HIF2β expressions in bone metastatic clear cell renal cell cancer

    DEFF Research Database (Denmark)

    Szendroi, Attila; Szász, A. Marcell; Kardos, Magdolna

    2016-01-01

    BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1β/HIF2β and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2β was lower in mRCC both at m...

  17. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Guo, Guangwu; Gui, Yaoting; Gao, Shengjie

    2012-01-01

    We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of similar to 1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the u...

  18. Palliative percutaneous kidney embolization with enbucrilate in patients with renal cell carcinoma: safety and symptom control.

    Science.gov (United States)

    Serafin, Zbigniew; Karolkiewicz, Maciej; Strześniewski, Piotr; Lasek, Władysław; Bryczkowski, Michał; Wolski, Zbigniew

    2007-05-01

    Primarily palliative renal embolization is a relatively rare procedure which is indicated in patients with unresectable kidney malignancies and in patients in poor general condition. The aim of this paper was to evaluate the role of primarily palliative transarterial renal embolization for the treatment of inoperable patients with renal cell carcinoma, assessing the indications, safety, and efficacy of this procedure. Seventy-three patients scheduled for palliative embolization between 1998 and 2005 were retrospectively analyzed regarding their medical history, the procedure report, and data from the early postoperative period. Sixty-six of the 73 patients presented with renal cell carcinoma stage IV. The most common indication for embolization was hematuria (34%), followed by flank pain (32%), prophylaxis in stage IV (25%), lack of consent for surgery (7%), and poor general condition (3%). Embolizations were performed under local anesthesia with a mixture of enbucrilate and iodinated oil, with the use of additional embolizing materials in two cases. The procedure eliminated hematuria in 100% of cases and removed the loin pain completely in 72%. Migration of the embolizing material was observed in 10% of cases, and in 4% it resulted in symptomatic occlusion of the lower extremity distal arteries. Postembolic syndrome was noted in 92% of the patients Percutaneous palliative embolization with enbucrilate is a safe and effective method of treating patients with unresectable renal cell carcinoma. The potential effect of the embolization on cancer progression and improvement of survival in these patients still requires prospective investigation.

  19. Renal diagnosis of chronic hemodialysis patients with urinary tract transitional cell carcinoma in Taiwan.

    Science.gov (United States)

    Chang, Chung-Hsin; Yang, Cheng-Ming; Yang, An-Hang

    2007-04-15

    Transitional cell carcinoma (TCC) is the most common malignancy in dialysis patients of Taiwan. The reason for such a high incidence of TCC is undetermined. The correlation between the underlying renal disease and the development of TCC was investigated. The authors retrospectively reviewed the clinical data and outcome of 1537 chronic hemodialysis (HD) patients from 1993 to 2002. The incidence of TCC was computed. The Cox regression method was used to analyze the role of potential risk factors. After a mean dialysis duration of 46.5 months, 26 (1.69%) patients with TCC were diagnosed. The standardized incidence ratio (SIR) of TCC was 48.2 as compared with the general population and the SIR of TCC seemed higher in women (65.1) and in the age group 50 to 54 years (173.6). Of them, most cases showed no definite etiology. All these cases showed bilateral contracted kidneys. Nonnephrotic proteinuria was found in all cases and trace glucosuria was found in 17 (65%). Painless gross hematuria was the cardinal symptom and distant metastasis was rare. Also, TCC in upper urinary tracts were common and found in 14 (54%) of patients. Age at the time of dialysis, female sex, compound analgesic use, and Chinese herb use had statistical significance as risk factors (P Taiwan, especially in female and middle-aged patients. The study indicated that chronic tubulointerstitial nephritis (CTIN) is the most likely underlying renal disease in HD patients with TCC, a high percentage of the CTIN related to the usage of Chinese herbs or compound analgesics may contribute to the development of TCC, whereas diabetes or chronic glomerulonephritis play only a minor role.

  20. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report

    OpenAIRE

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

    2017-01-01

    Background Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the fie...

  1. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience.

    Science.gov (United States)

    Coelho, Rafael Corrêa; Reinert, Tomás; Campos, Franz; Peixoto, Fábio Affonso; de Andrade, Carlos Augusto; Castro, Thalita; Herchenhorn, Daniel

    2016-01-01

    The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS. Copyright© by the International Brazilian Journal of Urology.

  2. Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA experience

    Directory of Open Access Journals (Sweden)

    Rafael Corrêa Coelho

    Full Text Available ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC treated by the Brazilian Unified Health System (SUS at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%, with a median age of 58 years. Nephrectomy was performed in 41 (71% patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2% patients. In 50 patients (86%, sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%, hypothyroidism (43%, mucositis (33% and diarrhea (29%. Grade 3 and 4 adverse effects were infrequent: fatigue (12%, hypertension (12%, thrombocytopenia (7%, neutropenia (5% and hand-foot syndrome (5%. Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

  3. Development of a living membrane comprising of a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane

    NARCIS (Netherlands)

    Schophuizen, C.M.S.; De Napoli, Ilaria; Jansen, J.; Da Silva Teixeira, Sandra; Wilmer, M.; Hoenderop, J.G.; van den Heuvel, L.P.W.; Masereeuw, R.; Stamatialis, Dimitrios

    2015-01-01

    The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a “living membrane”, consisting of a tight kidney cell monolayer with preserved functional organic ion

  4. Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.

    Science.gov (United States)

    Asma, Gati; Amal, Gorrab; Raja, Marrakchi; Amine, Derouiche; Mohammed, Chebil; Amel, Ben Ammar Elgaaied

    2015-05-01

    The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

  5. Bariatric Surgery to Target Obesity in the Renal Transplant Population: Preliminary Experience in a Single Center.

    Science.gov (United States)

    Gazzetta, P G; Bissolati, M; Saibene, A; Ghidini, C G A; Guarneri, G; Giannone, F; Adamenko, O; Secchi, A; Rosati, R; Socci, C

    2017-05-01

    During the last century, obesity has become a global epidemic. The effect of obesity on renal transplantation may occur in perioperative complications and impairment of organ function. Obese patients have metabolic derangements that can be exacerbated after transplantation and obesity directly impacts most transplantation outcomes. These recipients are more likely to develop adverse graft events, such as delayed graft function and early graft loss. Furthermore, obesity is synergic to some immunosuppressive agents in triggering diabetes and hypertension. As behavioral weight loss programs show disappointing results in these patients, bariatric surgery has been considered as a means to achieve rapid and long-term weight loss. Up-to-date literature shows laparoscopic bariatric surgery is feasible and safe in transplantation candidates and increases the rate of transplantation eligibility in obese patients with end-stage organ disease. There is no evidence that restrictive procedures modify the absorption of immunosuppressive medications. From 2013 to 2016 we performed six bariatric procedures (sleeve gastrectomy) on obese patients with renal transplantation; mean preoperative body mass index (BMI) was 39.8 kg/m 2 . No postoperative complication was observed and no change in the immunosuppressive medications regimen was needed. Mean observed estimated weight loss was 27.6%, 44.1%, 74.2%, and 75.9% at 1, 3, 6, and 12 months follow-up, respectively. Our recommendation is to consider patients with BMI >30 kg/m 2 as temporarily ineligible for transplantation and as candidates to bariatric surgery if BMI >35 kg/m 2 . We consider laparoscopic sleeve gastrectomy as a feasible, first-choice procedure in this specific population. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Zhenyu Qiu

    2014-08-01

    Full Text Available Objective This study aims to observe the function of umbilical cord-mesenchymal stem cells (UC-MSCs labelled with enhanced green fluorescent protein (eGFP in the repair of renal ischaemia-reperfusion (I/R injury, to determine the effects on inflammatory cascade in an established rat model and to explore possible pathogenesis. Materials and Methods Sixty rats were randomly divided into three groups: the sham-operated, I/R and UC-MSC treatment groups. All rats underwent right nephrectomy. Ischaemia was induced in the left kidney by occlusion of the renal artery and vein for 1hour, followed by reperfusion for 24 hours or 48 hours. Kidney samples were collected to observe morphological changes. Immunohistochemistry was performed to assess the expression of intercellular adhesion molecule 1 (ICAM-1 in the renal tissue sample, as well as the number of infiltrating polymorphonuclear neutrophils (PMNLs and UC-MSCs with positive eGFP. Results Renal histopathological damages and the expression of ICAM-1 and PMNL increased significantly in the I/R group compared with those in the sham-operated group, whereas the damages were less conspicuous in the UC-MSC treatment group. Conclusions Renal ICAM-1, which mediated PMNL infiltration and contributed to renal damage, was significantly up-regulated in the I/R group. UC-MSCs were identified to inhibit these pathological processes and protect the kidney from I/R injury.

  7. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

    Directory of Open Access Journals (Sweden)

    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  8. Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells.

    Science.gov (United States)

    Payne, Emily H; Ramalingam, Dhivya; Fox, Donald T; Klotman, Mary E

    2018-01-15

    Prior studies have found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy have remained unclear. Here we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). We found that as in many cell types, Vpr first initiates G 2 cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy. Specifically, we found that a fraction of G 2 -arrested RTECs reenter the cell cycle. Following this cell cycle reentry, two distinct outcomes occur. Cells that enter complete mitosis undergo mitotic cell death due to extra centrosomes and aberrant division. Conversely, cells that abort mitosis undergo endoreplication to become polyploid. We further show that multiple small-molecule inhibitors of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including those that target ATR, ATM, and mTOR, indirectly prevent Vpr-mediated polyploidy by preventing G 2 arrest. In contrast, an inhibitor that targets DNA-dependent protein kinase (DNA-PK) specifically blocks the Vpr-mediated transition from G 2 arrest to polyploidy. These findings outline a temporal, molecularly regulated path to polyploidy in HIV-positive renal cells. IMPORTANCE Current cure-focused efforts in HIV research aim to elucidate the mechanisms of long-term persistence of HIV in compartments. The kidney is recognized as one such compartment, since viral DNA and mRNA persist in the renal tissues of HIV-positive patients. Further, renal disease is a long-term comorbidity in the setting of HIV. Thus, understanding the regulation and impact of HIV infection on renal cell biology will provide important insights into this unique HIV compartment. Our work identifies mechanisms that distinguish

  9. Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

    International Nuclear Information System (INIS)

    Mellas, J.; Hammerman, M.R.

    1986-01-01

    We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

  10. Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

    Science.gov (United States)

    Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

    2012-01-01

    IClswell can be ruled out. Furthermore, we show that curcumin exposure induces apoptosis in human kidney cells, and at a concentration of 5.0–10 μM induces the appearance of a sub-population of cells with a dramatically increased volume. In these cells the regulation of the cell volume seems to be impaired, most likely as a consequence of the IClswell blockade. Similarly, 50 μM curcumin induced apoptosis, caused cell cycle arrest in G1-phase and increased the volume of human colorectal adenocarcinoma HT-29 cells. The cell cycle arrest in G1 phase may be the mechanism underlying the volume increase observed in this cell line after exposure to curcumin. PMID:22178266

  11. Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

    International Nuclear Information System (INIS)

    Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

    2012-01-01

    swell can be ruled out. Furthermore, we show that curcumin exposure induces apoptosis in human kidney cells, and at a concentration of 5.0–10 μM induces the appearance of a sub-population of cells with a dramatically increased volume. In these cells the regulation of the cell volume seems to be impaired, most likely as a consequence of the ICl swell blockade. Similarly, 50 μM curcumin induced apoptosis, caused cell cycle arrest in G1-phase and increased the volume of human colorectal adenocarcinoma HT-29 cells. The cell cycle arrest in G1 phase may be the mechanism underlying the volume increase observed in this cell line after exposure to curcumin.

  12. Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study.

    Science.gov (United States)

    Hayden, Derek; McCarthy, Christine; Akijian, Layan; Callaly, Elizabeth; Ní Chróinín, Danielle; Horgan, Gillian; Kyne, Lorraine; Duggan, Joseph; Dolan, Eamon; O' Rourke, Killian; Williams, David; Murphy, Sean; O'Meara, Yvonne; Kelly, Peter J

    2017-10-01

    Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m 2 , renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m 2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m 2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

  13. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  14. Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Mohammad S Alzahri

    2015-01-01

    Full Text Available Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.

  15. β-Catenin promotes cell proliferation, migration, and invasion but induces apoptosis in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yang CM

    2017-02-01

    Full Text Available Chun-ming Yang,1 Shan Ji,2 Yan Li,3 Li-ye Fu,3 Tao Jiang,3 Fan-dong Meng31Department of Urology, The First Affiliated Hospital, China Medical University, 2Department of Endocrinology, The Fifth People’s Hospital of Shenyang, 3Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital, China Medical University, Shenyang, ChinaAbstract: β-Catenin (CTNNB1 gene coding protein is a component of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. Abnormal accumulation of CTNNB1 contributes to most cancers. This research studied the involvement of β-catenin in renal cell carcinoma (RCC cell proliferation, apoptosis, migration, and invasion. Proliferation, cell cycle, and apoptosis were analyzed by using Cell Counting Kit-8 and by flow cytometry. Migration and invasion assays were measured by transwell analysis. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of CTNNB1, ICAM-1, VCAM-1, CXCR4, and CCL18 in RCC cell lines. It was found that CTNNB1 knockdown inhibited cell proliferation, migration, and invasion and induced apoptosis of A-498 cells. CTNNB1 overexpression promoted cell proliferation, migration, and invasion and inhibited apoptosis of 786-O cells. Moreover, knockdown of CTNNB1 decreased the levels of ICAM-1, VCAM-1, CXCR4, and CCL18 expression, but CTNNB1 overexpression increased the expression of ICAM-1, VCAM-1, CXCR4, and CCL18. Further in vivo tumor formation study in nude mice indicated that inhibition of CTNNB1 delayed the progress of tumor formation through inhibiting PCNA and Ki67 expression. These results indicate that CTNNB1 could act as an oncogene and may serve as a promising therapeutic strategy for RCC.Keywords: kidney cancer, oncogene, β-catenin, survival time, tumor migration-related protein

  16. Mitochondrial Sirt3 supports cell proliferation by regulating glutamine-dependent oxidation in renal cell carcinoma

    International Nuclear Information System (INIS)

    Choi, Jieun; Koh, Eunjin; Lee, Yu Shin; Lee, Hyun-Woo; Kang, Hyeok Gu; Yoon, Young Eun; Han, Woong Kyu; Choi, Kyung Hwa; Kim, Kyung-Sup

    2016-01-01

    Clear cell renal carcinoma (RCC), the most common malignancy arising in the adult kidney, exhibits increased aerobic glycolysis and low mitochondrial respiration due to von Hippel-Lindau gene defects and constitutive hypoxia-inducible factor-α expression. Sirt3 is a major mitochondrial deacetylase that mediates various types of energy metabolism. However, the role of Sirt3 as a tumor suppressor or oncogene in cancer depends on cell types. We show increased Sirt3 expression in the mitochondrial fraction of human RCC tissues. Sirt3 depletion by lentiviral short-hairpin RNA, as well as the stable expression of the inactive mutant of Sirt3, inhibited cell proliferation and tumor growth in xenograft nude mice, respectively. Furthermore, mitochondrial pyruvate, which was used for oxidation in RCC, might be derived from glutamine, but not from glucose and cytosolic pyruvate, due to depletion of mitochondrial pyruvate carrier and the relatively high expression of malic enzyme 2. Depletion of Sirt3 suppressed glutamate dehydrogenase activity, leading to impaired mitochondrial oxygen consumption. Our findings suggest that Sirt3 plays a tumor-progressive role in human RCC by regulating glutamine-derived mitochondrial respiration, particularly in cells where mitochondrial usage of cytosolic pyruvate is severely compromised. -- Highlights: •Sirt3 is required for the maintenance of RCC cell proliferation. •Mitochondrial usage of cytosolic pyruvate is severely compromised in RCC. •Sirt3 supports glutamine-dependent oxidation in RCC.

  17. Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells.

    Science.gov (United States)

    Yao, Ling; Chen, Ruifang; Wang, Pu; Zhang, Qi; Tang, Hailiang; Sun, Huaping

    2016-01-01

    Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts. These iPSCs show pluripotency in vitro and in vivo, as evidenced by expression of pluripotency associated genes, differentiation into three embryonic germ layers by teratoma tests, as well as neuronal fate specification by embryoid body formation. Moreover, the four exogenous genes are effectively silenced in these iPSCs. This study highlights the use of hERCCs to generate highly functional human iPSCs which may aid the study of genetic kidney diseases and accelerate the development of cell-based regenerative therapy.

  18. Mitochondrial Sirt3 supports cell proliferation by regulating glutamine-dependent oxidation in renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jieun; Koh, Eunjin; Lee, Yu Shin; Lee, Hyun-Woo; Kang, Hyeok Gu [Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoon, Young Eun; Han, Woong Kyu [Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Choi, Kyung Hwa [Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam 463-712 (Korea, Republic of); Kim, Kyung-Sup, E-mail: KYUNGSUP59@yuhs.ac [Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2016-06-03

    Clear cell renal carcinoma (RCC), the most common malignancy arising in the adult kidney, exhibits increased aerobic glycolysis and low mitochondrial respiration due to von Hippel-Lindau gene defects and constitutive hypoxia-inducible factor-α expression. Sirt3 is a major mitochondrial deacetylase that mediates various types of energy metabolism. However, the role of Sirt3 as a tumor suppressor or oncogene in cancer depends on cell types. We show increased Sirt3 expression in the mitochondrial fraction of human RCC tissues. Sirt3 depletion by lentiviral short-hairpin RNA, as well as the stable expression of the inactive mutant of Sirt3, inhibited cell proliferation and tumor growth in xenograft nude mice, respectively. Furthermore, mitochondrial pyruvate, which was used for oxidation in RCC, might be derived from glutamine, but not from glucose and cytosolic pyruvate, due to depletion of mitochondrial pyruvate carrier and the relatively high expression of malic enzyme 2. Depletion of Sirt3 suppressed glutamate dehydrogenase activity, leading to impaired mitochondrial oxygen consumption. Our findings suggest that Sirt3 plays a tumor-progressive role in human RCC by regulating glutamine-derived mitochondrial respiration, particularly in cells where mitochondrial usage of cytosolic pyruvate is severely compromised. -- Highlights: •Sirt3 is required for the maintenance of RCC cell proliferation. •Mitochondrial usage of cytosolic pyruvate is severely compromised in RCC. •Sirt3 supports glutamine-dependent oxidation in RCC.

  19. Correlation between the trajectory of systolic blood pressure and new renal damage in a nonhypertensive population.

    Science.gov (United States)

    Wang, Zhi-Jun; Jia, Dao; Tian, Jun; Liu, Jie; Li, Li-Jie; Huang, Yu-Ling; Cao, Xin-Ying; Ning, Chun-Hong; Zhao, Quan-Hui; Yu, Jun-Xing; Zhang, Rui-Ying; Zhang, Ya-Jing; Gao, Jing-Sheng; Wu, Shou-Ling

    2017-10-01

    This study aims to investigate the correlation between the trajectory of systolic blood pressure (SBP) and new renal damage in a nonhypertensive population. This prospective cohort study included a total of 14 382 nonhypertensive individuals, employees of Kailuan Group of Companies, who took part in five healthy examinations in 2006-2007, 2008-2009, 2010-2011, 2012-2013, and 2014-2015, and had complete data. These individuals were divided into four groups according to the different trajectories of SBP: low-low, low-stable, middle-high, and high-high groups. The correlation between the trajectory of SBP and new renal damage in a nonhypertensive population was analyzed using a multivariate Cox's proportional hazard regression model. (a) A total of 14 382 individuals had complete data and the average age of these individuals was 44.6±10.8 years. Among these, 10 888 (75.7%) individuals were men and 3494 (24.3%) individuals were women. (b) These individuals were divided into four groups according to different trajectories of blood pressure: low-low group, accounting for 13.15% (blood pressure was group, accounting for 53.91% (blood pressure was between 115 and 116 mmHg); middle-high group, accounting for 28.77% (blood pressure was between 125 and 131 mmHg); and high-high group, accounting for 4.6% (blood pressure was between 126 and 151 mmHg). (c) With the increase in the trajectory of SBP, the detection rate of renal damage increased gradually. From the low-low group to the high-high group, the detection rates of estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m were 2.3, 2.4, 3.6, and 4.3%, respectively; the positive rates of urinary protein were 1.7, 2.9, 3.8, and 5.5%, respectively; and the detection rates of eGFR less than 60 ml/min/1.73 m or positive urinary protein were 4, 5.2, 7.3, and 9.3%, respectively (Pgroup, the risk of eGFR less than 60 ml/min/1.73 m increased by nearly 1.5 times in the high-high group and in

  20. Population pharmacokinetics of teicoplanin in hospitalized elderly patients using cystatin C as an indicator of renal function.

    Science.gov (United States)

    Kasai, Hidefumi; Tsuji, Yasuhiro; Hiraki, Yoichi; Tsuruyama, Moeko; To, Hideto; Yamamoto, Yoshihiro

    2018-04-01

    Serum cystatin C (CysC) has recently been proposed as an alternative marker to serum creatinine (SCR) for estimating renal clearance. In the present study, we performed a population pharmacokinetic analysis of teicoplanin (TEIC), which is mainly eliminated through the kidneys, using CysC as a predictor for renal clearance. Thirty-six patients with MRSA infections who were administrated to the National Hospital Organization Beppu Medical Center between January 2012 and December 2013 were enrolled and gave 123 sets of blood TEIC concentration data. Renal clearance was estimated by the Hoek equation using CysC, by creatinine clearance predicted by the Cockcroft-Gault equation using SCR, or directly by CysC. One compartment open model with inter-individual variabilities for renal clearance and the volume of distribution as well as an additional residual error model was used to estimate population pharmacokinetic parameters for TEIC. The model with the best predictability was that with CysC as a predictor for renal clearance; it showed better significance than the models using estimated the glomerular filtration rate by the Hoek equation or CLcr. The final model was as follows: CL (L/hr) = 0.510 × (CysC/1.4) -0.68  × Total body weight/60 0.81 , omega (CL) = 19.8% CV, VC (L) = 78.1, omega (V) = 42.7% CV. The present results show the usefulness of CysC to more accurately predict the pharmacokinetics of drugs mainly eliminated through the kidneys, such as TEIC. However, since the sample size in this study was relatively small, further investigations on renal clearance predictability using CysC are needed. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Radiofrequency ablation of renal cell carcinoma under CT guidance. Present and Future status

    International Nuclear Information System (INIS)

    Nasu, Yasutomo; Kobayashi, Yasuyuki; Uematsu, Katsutoshi; Saika, Takashi; Kumon, Hiromi; Gohara, Hideo; Mimura, Hidefumi; Kanazawa, Susumu

    2011-01-01

    At Okayama University, radiofrequency ablation (RFA) of renal cell carcinoma was performed in May 2002 as the initial case in Japan. In 2004, it was regarded as an advanced medical technique by the Japanese authority. Since then, RFA has been actively performed for renal cell carcinoma not only at the primary site but also at the metastatic site, including the lung and bone. The clinical outcome has been compatible with other institutes and no serious adverse events have occurred. From the view paint of fusing technical innovation with medical safety, this treatment is a potent therapeutic option for renal cell carcinoma. In the era of laparoscopic surgery, RFA is indicated for cases with von Hippel-Lindau disease (VHL), recurrence after partial nephrectomy, a single kidney and intolerance to general anesthesia, due to its technical advantage in that RFA can be repeated. In this review, the current clinical outcome is reported and future prospects are discussed as to whether it can be the safest and most concrete treatment for renal cell carcinoma in the 21 st century. (author)

  2. T-cells contribute to hypertension but not to renal injury in mice with subtotal nephrectomy

    NARCIS (Netherlands)

    Oosterhuis, Nynke R.; Papazova, Diana A.; Gremmels, Hendrik; Joles, Jaap A.; Verhaar, Marianne C.

    2017-01-01

    Background: The pathological condition of chronic kidney disease may not be adequately recapitulated in immunocompromised mice due to the lack of T-cells, which are important for the development of hypertension and renal injury. We studied the role of the immune system in relation to salt-sensitive

  3. Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical Insights and Practical Considerations

    NARCIS (Netherlands)

    Bex, A.; Fournier, L.; Lassau, N.; Mulders, P.F.A.; Nathan, P.; Oyen, W.J.G.; Powles, T.

    2014-01-01

    CONTEXT: The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to

  4. Duodenorenal Fistula as a Complication of Radiofrequency Ablation of Hepatic Metastasis of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Arman Erkan

    2017-06-01

    Full Text Available Duodenorenal fistula is a rare condition. The right kidney and the second part of the duodenum are in close anatomic proximity. Although unusual, fistulae can occur between these two anatomic structures. We report a patient who presented with duodenorenal fistula after radiofrequency ablation for renal cell carcinoma and its hepatic metastasis.

  5. Targeted therapy of renal cell carcinoma: synergistic activity of cG250-TNF and IFNg.

    NARCIS (Netherlands)

    Bauer, S.; Oosterwijk-Wakka, J.C.; Adrian, N.; Oosterwijk, E.; Fischer, E.; Wuest, T.; Stenner, F.; Perani, A.; Cohen, L.; Knuth, A.; Divgi, C.; Jager, D.; Scott, A.M.; Ritter, G.; Old, L.J.; Renner, C.

    2009-01-01

    Immunotherapeutic targeting of G250/Carbonic anhydrase IX (CA-IX) represents a promising strategy for treatment of renal cell carcinoma (RCC). The well characterized human-mouse chimeric G250 (cG250) antibody has been shown in human studies to specifically enrich in CA-IX positive tumors and was

  6. CD16(+) monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction

    NARCIS (Netherlands)

    Boersema, M.; van den Born, Joost; van Ark, J.; Harms, Geertruida; Seelen, M. A.; van Dijk, M. C. R. F.; van Goor, H.; Navis, G. J.; Popa, E. R.; Hillebrands, J. L.

    In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal alpha-SMA(+) smooth muscle-like cells are present in human renal

  7. Linear IgA bullous dermatosis in a patient with renal cell carcinoma

    NARCIS (Netherlands)

    Van der Waal, RIF; Van de Scheur, MR; Pas, HH; Jonkman, MF; Van Groeningen, CJ; Nieboer, C; Starink, TM

    Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal bullous disease with heterogeneous clinical manifestations, characterized by linear deposition of IgA along the epidermal basement membrane zone. We report a patient with a metastasized renal cell carcinoma who developed an extensive

  8. Body Composition in Relation to Clinical Outcomes in Renal Cell Cancer

    NARCIS (Netherlands)

    Vrieling, Alina; Kampman, Ellen; Knijnenburg, Nathalja C.; Mulders, Peter F.; Sedelaar, J.P.M.; Baracos, Vickie E.; Kiemeney, Lambertus A.

    2016-01-01

    Context: Several studies suggest that body composition (ie, body proportions of muscle and fat defined by computed tomography) is associated with clinical outcomes of several cancer types, including renal cell cancer (RCC). Objective: To conduct a systematic review and meta-analysis of the evidence

  9. Targeted therapies for renal cell carcinoma: review of adverse event management strategies.

    NARCIS (Netherlands)

    Eisen, T.; Sternberg, C.N.; Robert, C.; Mulders, P.F.; Pyle, L.; Zbinden, S.; Izzedine, H.; Escudier, B.

    2012-01-01

    With the advent of targeted agents for the treatment of renal cell carcinoma (RCC), overall survival has improved, and patients are being treated continuously for increasingly long periods of time. This has raised challenges in the management of adverse events (AEs) associated with the six targeted

  10. Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Penttilä, P; Donskov, F; Rautiola, J

    2017-01-01

    BACKGROUND: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. PATIENTS AND METHODS: Eighty-five mRCC patients received everolimus at Helsinki University...

  11. Metastasis is promoted by a bioenergetic switch: New targets for progressive renal cell cancer

    NARCIS (Netherlands)

    Langbein, Sigrun; Frederiks, Wilma M.; zur Hansen, Axel; Popa, Juljane; Lehmann, Jan; Weiss, Christel; Alken, Peter; Coy, Johannes F.

    2008-01-01

    Targeted therapies have demonstrated clinical benefit with limited impact on long-term disease specific survival in the treatment of renal cell cancer (RCC). New opportunities for the treatment of tumors that are resistant or have relapsed, are needed. Increased anaerobic glucose fermentation to

  12. Amplification of epidermal growth factor receptor gene in renal cell carcinoma

    DEFF Research Database (Denmark)

    El-Hariry, Iman; Powles, Thomas; Lau, Mike R

    2010-01-01

    Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2...

  13. Assessment of renal function in children with sickle cell anaemia in ...

    African Journals Online (AJOL)

    Assessment of renal function in children with sickle cell anaemia in University of Maiduguri Teaching Hospital. A.G. Farouk, A.H. Elechi, M.S. Yauba, M.G. Mustapha, B.A. Ibrahim, H.A. Ibrahim, L.M. Ibrahim, J.P. Ambe ...

  14. Delirium after interleukin-2 and alpha-interferon therapy for renal cell carcinoma

    NARCIS (Netherlands)

    Van Steijn, JHM; Nieboer, P; Hospers, GAP; De Vries, EGE; Mulder, NH

    2001-01-01

    A 55-year-old man receiving alpha-interferon and interieukin-2 therapy for renal cell carcinoma presented with seizures and delirium. A CT-scan of the cerebrum did not reveal any disorder. Both alpha-interferon and interleukin-2 were stopped Treatment with steroids led to complete regression of

  15. The role of HUCB derived stem cells therapy in repair of renal ...

    African Journals Online (AJOL)

    Dr Olaleye Samuel

    and improvement of renal function in cisplatin-induced ARF model. Forty four rats ... 88.9% of animals in MSCs treated rats versus 87.5% in CD34+ cells treated rats. HUCB derived .... containing 5 ml of citrate phosphate dextrose adenine-1.

  16. Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

    DEFF Research Database (Denmark)

    de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael

    2014-01-01

    Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty...

  17. Can duplex Doppler ultrasound replace computerized tomography in staging patients with renal cell carcinoma?

    NARCIS (Netherlands)

    Bos, SD; Mensink, HJA

    The purpose of this study was to evaluate the accuracy and reliability of duplex Doppler ultrasound (US) and computerized tomography (CT) in staging patients with renal cell carcinoma (RCC). Sixty-six patients were evaluated pre-operatively with duplex Doppler ultrasound and CT. The results were

  18. Sciatica leading to the discovery of a renal cell carcinoma | Lakmichi ...

    African Journals Online (AJOL)

    Metastatic renal cell cancer is not exceptional in kidney cancer (30% of patients with kidneyl cancer). Its prognosis is particularly severe. However, sciatic neuralgia (sciatica) remains an exceptional revealing clinical sign of this disease. The authors report the case of a patient admitted with right sciatica as chief complain, ...

  19. Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

    DEFF Research Database (Denmark)

    Haaber, A B; Eidemak, I; Jensen, T

    1995-01-01

    Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

  20. Cost utility analysis of everolimus in the treatment of metastatic renal cell cancer in the Netherlands

    NARCIS (Netherlands)

    Mihajlović, J.; Minović, I.; Bruinsma, A.; Postma, M.J.

    2013-01-01

    Objectives: Metastatic renal cell cancer (mRCC) is becoming an important part of Dutch health care expenditure due to expensive pharmaceutical options for disease control and lack of adequate prevention methods. New targeted therapeutics, such as sunitinib, sorafenib and everolimus, have recently

  1. Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

    Science.gov (United States)

    Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

    2012-05-01

    Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  2. Renal cell cancer in Israel: sex and ethnic differences in incidence and mortality, 1980-2004.

    Science.gov (United States)

    Tarabeia, Jalal; Kaluski, Dorit Nitzan; Barchana, Micha; Dichtiar, Rita; Green, Manfred S

    2010-06-01

    The causes of renal cell cancer (RCC) remain largely unexplained. While the incidence is generally higher in men than in women, little has been reported on ethnic differences. We examine trends in RCC incidence and mortality rates among Israeli Arab and Jewish populations and compared with the rates in other countries. Age-adjusted RCC incidence and mortality rates in Israel, during 1980-2004, were calculated by sex and population group, using the National Cancer Registry. They were compared with the United States based on the Surveillance Epidemiology and End Results [SEER] program and the IARC database for international comparisons. While RCC incidence rates in Israel are similar to the United States and the European average, the rates are significantly higher among Israeli Jews than Arabs. Men are affected more than women. Incidence rates over the last 24 years have increased among all men and Jewish women, but not among Arab women. Among men, the incidence rate ratio for Jews to Arabs declined from 3.96 in 1980-1982 to 2.34 in 2001-2004, whereas for women there was no change. The mortality rates were higher among Jews than Arab and among men than women. There were no significant change in the mortality rates and rate ratios. Our findings demonstrate marked ethnic differences in RCC in Israel. The lower incidence among Arabs stands in contrast to the higher prevalence of potential risk factors for RCC in this population group. Genetic factors, diet and other lifestyle factors could play protective roles. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Phenotype heterogeneity in cancer cell populations

    International Nuclear Information System (INIS)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-01-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  4. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  5. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as "bet hedging" of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  6. Waist Circumference, Not Body Mass Index, Is Associated with Renal Function Decline in Korean Population: Hallym Aging Study

    Science.gov (United States)

    Oh, Hyunju; Quan, Shan Ai; Jeong, Jin-Young; Jang, Soong-Nang; Lee, Jung Eun; Kim, Dong-Hyun

    2013-01-01

    Background Prospective investigation of obesity and renal function decline in Asia is sparse. We examined the associations of body mass index (BMI) and waist circumference (WC) with renal function decline in a prospective study of Korean population. Methods A total of 454 participants who had baseline estimated glomerular filtration rate (eGFR) levels of more than 60 mL/min/1.73 m2 in Hallym Aging Study (HAS) were included and followed for 6 years. Renal function decline was defined as follows: (1) an eGFR decline ≥3 mL/min/1.73 m2/year (n = 82 cases); (2) an eGFR decrease of 20% or greater (n = 87 cases) at follow-up; (3) an eGFR decrease of 20% greater at follow-up or eGFR decline ≥3 mL/min/1.73 m2/year (n = 91 cases); and (4) an eGFR 95 cm in men or >90 cm in women with ≤90 cm in men or ≤85 cm in women, ORs (95% CIs) ranged from 2.31 (1.14–4.69) to 2.78 (1.19–6.50) for the 4 definitions of renal function decline (all p-values for trend Korean population. Our results provide important evidence that simple measurement of central fat deposition rather than BMI could predict decline in renal function in Korean population. PMID:23536858

  7. Renal cell carcinoma in long-term survivors of advanced stage neuroblastoma in early childhood

    International Nuclear Information System (INIS)

    Fleitz, Julie M.; Wootton-Gorges, Sandra L.; Kurzrock, Eric A.; Wyatt-Ashmead, Josephine; McGavran, Loris; Koyle, Martin; Odom, Lorrie F.; West, Daniel C.; Martin, Kenneth W.

    2003-01-01

    Renal cell carcinoma (RCC) is rare in children and comprises only 1-3% of all pediatric primary renal tumors. Recently, several case reports have described RCC developing in patients previously treated for advanced stage neuroblastoma (NB). Our experience with four patients treated for advanced stage NB during early childhood who developed RCC later in life are added to 14 others in the literature. These patients and our review of the literature suggest an association between RCC and NB that warrants further study. (orig.)

  8. Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

    International Nuclear Information System (INIS)

    Middel, Peter; Brauneck, Sven; Meyer, Werner; Radzun, Heinz-Joachim

    2010-01-01

    Renal cell carcinoma (RCC) represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs) in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking. We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated. The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between MIP-3α-producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, MIP-3β and SLC expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters. Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of MIP-3α favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3β induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response

  9. Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meyer Werner

    2010-10-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking. Methods We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated. Results The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between MIP-3α-producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, MIP-3β and SLC expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters. Conclusion Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of MIP-3α favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3β induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response.

  10. Renal Replacement Therapy in End-Stage Sickle Cell Nephropathy: Presentation of Two Cases and Literature Review

    International Nuclear Information System (INIS)

    Al-Mueilo, Samir H.

    2005-01-01

    Chronic renal failure develops in 4-18% of patients with sickle cell anemia. Hemodialysis and kidney transplant are viable options in the management of end-stage renal disease in patients with sickle cell diseases (SCD). Information on kidney disease among Saudi patients with SCD is non-existing. In this report, the clinical course of two adult males with end-stage sickle cell nephropathy from Eastern Saudi Arabia is described. Literature on renal replacement therapy in sickle cell anemia (SCA) is discussed. (author)

  11. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-01-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1 , collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  12. In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET

    International Nuclear Information System (INIS)

    Wong, Peter K.; Lee, Sze Ting; Murone, Carmel; Eng, John; Lawrentschuk, Nathan; Berlangieri, Salvatore University; Pathmaraj, Kunthi; O’Keefe, Graeme J.; Sachinidis, John; Byrne, Amanda J.; Bolton, Damien M.; Davis, Ian D.; Scott, Andrew M.

    2014-01-01

    The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. The SUVmax (maximum standardized uptake value) mean±SD for FLT in tumour was 2.59±1.27, compared to normal kidney (2.47±0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60±1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean ± SD of 13.3%±9.2 (range 2.2% - 36.3%). There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology

  13. Interaction between cellular retinoic acid-binding protein II and histone hypoacetylation in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2008-04-01

    Full Text Available Renal cell carcinoma is a rare but serious malignancy. Since a reduction in the level of retinoic acid receptor beta 2 (RARbeta2 expression in cancer cells due in part to histone hypoacetylation which is controlled by histone deacetylase (HD, the study on the interaction between cellular retinoic acid-binding proteins II (CRABP II, which is proposed to have its potential influence on retinoic acid (RA response, and HD can be useful. Comparing to CARBP II and HD, the CARBP II-HD poses the same function and biological process as HD. This can confirm that HD has a significant suppressive effect on the expression of CARBP II. Therefore, reduction in the level of RARbeta2 expression in cancer cells can be expected and this can lead to failure in treatment of renal cell carcinoma with RA. The author hereby purpose that additional HD inhibitor should be added into the regiment of RA to increase the effectiveness of treatment.

  14. Impact of preoperative chronic renal failure on liver transplantation: a population-based cohort study

    Science.gov (United States)

    Chung, Peter Chi-Ho; Chen, Hsiu-Pin; Lin, Jr-Rung; Liu, Fu-Chao; Yu, Huang-Ping

    2016-01-01

    Purpose The purpose of this study was to assess whether preoperative chronic renal failure (CRF) affects the rates of postoperative complications and survival after liver transplantation. Methods This population-based retrospective cohort study included 2,931 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. Patients were divided into two groups, based on the presence or absence of preoperative CRF. Results The overall estimated survival rate of liver transplantation recipients (LTRs) with preoperative CRF was significantly lower than that of patients without preoperative CRF (P=0.0085). There was no significant difference between the groups in terms of duration of intensive care unit stay, total hospital stay, bacteremia, postoperative bleeding, and pneumonia during hospitalization. Long-term adverse effects, including cerebrovascular disease and coronary heart disease, were not different between patients with versus without CRF. Conclusion These findings suggest that LTRs with preoperative CRF have a higher rate of mortality. PMID:28008264

  15. Stereotactic body radiotherapy for primary renal cell carcinoma and adrenal metastases.

    Science.gov (United States)

    Kothari, Gargi; Louie, Alexander V; Pryor, David; Vela, Ian; Lo, Simon S; Teh, Bin S; Siva, Shankar

    2017-09-01

    The incidence of renal cell carcinoma (RCC) and metastatic adrenal lesions continues to rise and present evolving complexities in terms of management. Technical challenges in treatment delivery are compounded by the setting of an ageing patient population with multiple medical co-morbidities. While the standard of care treatment for both primary RCC and oligometastatic adrenal lesions has typically been surgery, a number of patients may be medically or surgically inoperable, and for whom alternative options require consideration. Additionally, in metastatic disease, surgery presents an invasive option, sometimes with unacceptable risks of perioperative morbidity and therefore is considered a less desirable option to some. Stereotactic body radiotherapy (SBRT) is an established radiotherapy technique that is rapidly being incorporated into many radiotherapy departments, particu-larly with the increasing availability and capabilities of modern linear accelerators to deliver precise image guided treatment. There are considerable advantages of SBRT including its ability to provide a non-invasive ablative treatment with very few treatment sessions, with emerging evidence showing promising rates of local control (LC) and low associated mor-bidity. This review details the use of SBRT for primary RCC as well as adrenal metastases, focusing on issues including patient selection, technical considerations, and patient out-comes. Furthermore, this review explores some recent insights into the radiobiology of RCC, the immunomodulatory effects of SBRT, and the use of systemic agents with SBRT.

  16. Emerging growth factor receptor antagonists for the treatment of renal cell carcinoma.

    Science.gov (United States)

    Zahoor, Haris; Rini, Brian I

    2016-12-01

    The landscape of systemic treatment for metastatic renal cell carcinoma (RCC) has dramatically changed with the introduction of targeted agents including vascular endothelial growth factor (VEGF) inhibitors. Recently, multiple new agents including growth factor receptor antagonists and a checkpoint inhibitor were approved for the treatment of refractory metastatic RCC based on encouraging benefit shown in clinical trials. Areas covered: The background and biological rationale of existing treatment options including a brief discussion of clinical trials which led to their approval, is presented. This is followed by reviewing the limitations of these therapeutic options, medical need to develop new treatments and major goals of ongoing research. We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. Expert opinion: Recently approved growth factor receptor antagonists have shown encouraging survival benefit but associated drug toxicity is a major issue. Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, has similarly shown survival benefit and is well tolerated. With multiple options now available in this patient population, the right sequence of these agents remains to be determined.

  17. Management of metastatic renal cell carcinoma in patients with poor prognosis

    International Nuclear Information System (INIS)

    Bullock, Andrea; McDermott, David F; Atkins, Michael B

    2010-01-01

    An improved understanding of renal cell carcinoma (RCC) biology has translated into major advances in the treatment of patients with metastatic RCC in recent years. Clinical and pathologic criteria can be used to identify RCC patients with poor prognoses. Such patients, however, are often excluded from the cancer clinical trials that guide treatment recommendations. This article reviews available information on the management of patients with metastatic RCC and poor risk features, focusing on the role of vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) inhibitors. While patients with poor risk features have a more guarded outcome, treatment with temsirolimus has produced meaningful improvements in overall survival for this population. Definitive phase III trial data are lacking for the VEGF pathway inhibitors in patients with poor prognostic features. However, available data suggest that such patients tolerate VEGF pathway blockade reasonably well and are likely to achieve some benefit relative to treatment with interferon. Ongoing translational research efforts may help to define novel treatment approaches specific for patients with metastatic RCC and poor prognostic features

  18. Radiological and cytological detection of renal pelvic transitional-cell carcinoma

    International Nuclear Information System (INIS)

    Paeivaensalo, M.; Merikanto, J.; Myllylae, V.; Hellstroem, P.; Kallionen, M.; Jalovaara, P.; Oulu Univ.; Oulu Univ.

    1990-01-01

    We evaluated US, CT, intraveneous urography, arteriography, retrograde pyelography and urine cytology results in a series of 23 patients with renal pelvic transitional-cell carcinomas, 14 of whom underwent US, 17 i.v. urography, 8 CT, 15 arteriography, 9 retrograde pyelography, and 17 patients urine cytology. A tumour was identified in 5 patients (36%) at US, in 11 patients (61%) at urography, in 7 (88%) at CT, in 10 patients (67%) at arteriography, and in 8 (89%) at retrograde pyelography. Urine cytology was assessed as showing changes consistent with Papanicolaou class III-V in 15 (88%) of 17 patients. When renal pelvic cancer is suspected, intravenous urography should be performed as the initial radiological examination and followed by CT, which may also identify tumour spread. Arteriography and retrograde pyelography are sometimes complementary investigations. Repeated urinary cytology is mandatory. Our results show that US alone is unreliable in detecting renal pelvic cancer. (orig.) [de

  19. Autocrine CSF-1 and CSF-1 Receptor Co-expression Promotes Renal Cell Carcinoma Growth

    Science.gov (United States)

    Menke, Julia; Kriegsmann, Jörg; Schimanski, Carl Christoph; Schwartz, Melvin M.; Schwarting, Andreas; Kelley, Vicki R.

    2011-01-01

    Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Co-expression of the monocytic growth factor CSF-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and anti-apoptosis during regeneration of renal tubules. Here we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were co-expressed in RCC and TEC proximally adjacent to RCC. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and EGF signaling in RCC. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R and EGF expression in RCC. Further, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCC. PMID:22052465

  20. Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats.

    Science.gov (United States)

    Peng, Tao; Wang, Jie; Zhen, Junhui; Hu, Zhao; Yang, Xiangdong

    2014-07-01

    The aim of this study was to investigate the effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty male Sprague-Dawley rats were included in the present study. Eight of the 30 rats were randomly selected and served as the normal control group (N group), while the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic rat model. Rats with diabetes were randomly divided into the diabetic (DM group) and benazepril (B group) groups. The total course was conducted over 12 weeks. Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured at the start and end of the study. We observed the tubulointerstitial pathological changes, and applied immunohistochemistry and western blotting to detect the expression of α-smooth muscle actin (α-SMA) in renal tissue. The levels of blood glucose, kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen and tubulointerstitial damage index (TII) in the DM group were significantly higher than that in the N group (pbenazepril significantly reduced the expression of α-SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the transdifferentiation of renal tubular epithelial cells and played an important role in kidney protection.

  1. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    OpenAIRE

    Christopher J. Ricketts; Aguirre A. De Cubas; Huihui Fan; Christof C. Smith; Martin Lang; Ed Reznik; Reanne Bowlby; Ewan A. Gibb; Rehan Akbani; Rameen Beroukhim; Donald P. Bottaro; Toni K. Choueiri; Richard A. Gibbs; Andrew K. Godwin; Scott Haake

    2018-01-01

    Summary: Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of sub...

  2. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn

    2008-01-01

    Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype......, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients...

  3. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    Directory of Open Access Journals (Sweden)

    Oliveira Jorge

    2007-07-01

    Full Text Available Abstract Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC, 13 papillary (pRCC, 10 chromophobe (chRCC, and 10 oncocytomas and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007, PTGS2 (p = 0.002, and RASSF1A (p = 0.0001. CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively, whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004. RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035. In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031 and nuclear grade (p = 0.022, respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

  4. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    International Nuclear Information System (INIS)

    Costa, Vera L; Henrique, Rui; Ribeiro, Franclim R; Pinto, Mafalda; Oliveira, Jorge; Lobo, Francisco; Teixeira, Manuel R; Jerónimo, Carmen

    2007-01-01

    Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively. The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses

  5. Renal endogenous stem cells: a new source for regenerative medicine in preterms?

    Directory of Open Access Journals (Sweden)

    Gavino Faa

    2015-10-01

    Full Text Available The creation of new medical approaches based on stem cells to treat chronic kidney disease (CKD and in particular end stage renal disease (ESRD has become imperative in recent years, due to the significant burdens of patients affected by renal failure and to the limitations of dialysis and kidney transplantation to solve the problem. The initial prospective of utilizing stem cells for regenerating the affected kidney has been at the basis of excitement and hope for all patients affected by ESRD. Unfortunately, too many challenges have halted the possibility to make such regenerative approach a reality, and the vast majority of patients with CKD and renal insufficiency experience a reduced quality of life associated with high mortality. The problem appears particularly severe when ESDR develops in childhood. Children submitted to kidney transplantation have a 95% of survival rate at 5 years, but only 66% of them survive at 20 years after renal transplant. As a result, patients transplanted in childhood will need repeated renal transplants during their life.Renal regenerative medicine might experience a major renaissance in the next years, developing new methodologies stemmed from the previous attempts. Here, we present some major points to be addressed, in order to open a debate on the potential offered by the different regenerative methodologies:the “exogenous” approach; the “endogenous” approach; the “therapeutic” approach; the “prevention” approach. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the Netherlands, Gavino Faa (Cagliari, Italy, Antonio Giordano (Philadelphia, USA

  6. Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

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    Kohan Donald E

    2002-08-01

    Full Text Available Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx, the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN, human glomerular visceral epithelial (HGEC and human proximal tubule (HPT cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. Results Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor by any cell type at any time point. Conclusion These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.

  7. High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

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    Daisuke Ogawa

    2011-01-01

    Full Text Available Metallothionein (MT is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2 are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

  8. Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases.

    Science.gov (United States)

    Trpkov, Kiril; Athanazio, Daniel; Magi-Galluzzi, Cristina; Yilmaz, Helene; Clouston, David; Agaimy, Abbas; Williamson, Sean R; Brimo, Fadi; Lopez, Jose I; Ulamec, Monika; Rioux-Leclercq, Nathalie; Kassem, Maysoun; Gupta, Nilesh; Hartmann, Arndt; Leroy, Xavier; Bashir, Samir Al; Yilmaz, Asli; Hes, Ondřej

    2018-04-01

    To further characterise biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC. We identified 28 tumours from multiple institutions. They typically showed two cell populations-larger cells with eosinophilic cytoplasm and higher-grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumour, range 5-100%); emperipolesis was found in all cases. The male/female ratio was 2:1, and the median age was 55 years (range 39-86 years). The median tumour size was 20 mm (range 9-65 mm). Pathological stage pT1a was found in 21 cases, pT1b in three, and pT3a and pT3b in one each (two not available). Multifocality was found in 32%: multifocal biphasic RCC in one case, biphasic + papillary RCC in two cases, biphasic + clear cell RCC in three cases, biphasic + low-grade urothelial carcinoma of the renal pelvis in one case, and biphasic + Birt-Hogg-Dubé syndrome in one case. Positive immunostains included: PAX8, cytokeratin (CK) 7, α-methylacyl-CoA racemase, epithelial membrane antigen, and vimentin. Cyclin D1 was expressed only in the larger cells. The Ki67 index was higher in the larger cells (median 5% versus ≤1%). Negative stains included: carbonic anhydrase 9, CD117, GATA-3, WT1, CK5/6, and CK20; CD10 and 34βE12 were variably expressed. Gains of chromosomes 7 and 17 were found in two evaluated cases. Follow-up was available for 23 patients (median 24 months, range 1-244 months): 19 were alive without disease, one was alive with recurrence, and one had died of disease (two had died of other causes). Biphasic papillary RCC is a rare variant of papillary RCC, and is often multifocal. © 2017 John Wiley & Sons Ltd.

  9. Regulation of renin secretion by renal juxtaglomerular cells

    DEFF Research Database (Denmark)

    Friis, Ulla G; Madsen, Kirsten; Stubbe, Jane

    2013-01-01

    A major rate-limiting step in the renin-angiotensin-aldosterone system is the release of active renin from endocrine cells (juxtaglomerular (JG) cells) in the media layer of the afferent glomerular arterioles. The number and distribution of JG cells vary with age and the physiological level...

  10. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

    Science.gov (United States)

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

    2017-11-30

    Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

  11. Diffusion-weighted imaging versus contrast-enhanced MR imaging for the differentiation of renal oncocytomas and chromophobe renal cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Yan; Wang, Haiyi; Shen, Yanguang; Ma, Lu; Pan, Jingjing; Ye, Huiyi [Chinese PLA General Hospital, Department of Radiology, Beijing (China); Guo, Aitao [Chinese PLA General Hospital, Department of Pathology, Beijing (China); Wang, Jia [Handan Central Hosptical, Department of Radiology, Hebei (China); Kang, Suhai [264 Hospital of PLA, X-ray Department, Taiyuan (China)

    2017-12-15

    To compare the performance of diffusion-weighted imaging (DWI) with that of contrast-enhanced MRI in differentiating renal oncocytomas from chromophobe renal cell carcinomas (RCCs). We recruited 48 patients with histopathologically confirmed renal oncocytomas (n=16) and chromophobe RCCs (n=32). All patients underwent preoperative DWI and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) and signal intensity were measured in each patient. ADC ratio and percentage of signal intensity change were calculated. Mean ADC values for renal oncocytomas were significantly higher than those for chromophobe RCCs (1.59±0.21 vs. 1.09±0.29 x 10{sup -3} mm{sup 2}/s, p < 0.001). Area under the ROC curve, sensitivity and specificity were 0.931, 87.5% and 84.4%, respectively, for ADC measurement of DW imaging; 0.825, 87.5% and 75%, respectively, for enhancement ratio (p > 0.05). Adding ADC values to the enhancement ratios in the ROC, analysis to differentiate renal oncocytoma from chromophobe RCCs increased specificity from 75 to 87.5% at 87.5% sensitivity without significantly increasing the AUC (0.930). Both DWI and contrast-enhanced MRI may assist in differentiating renal oncocytomas from chromophobe RCCs, with DWI showing higher diagnostic value. The combination of the two parameters could potentially provide better performance in distinguishing these two tumours. (orig.)

  12. Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal-cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: A case report.

    Directory of Open Access Journals (Sweden)

    Juan Ruiz-Bañobre

    2016-11-01

    Full Text Available Introduction: Papillary renal-cell carcinoma, which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programmed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus, but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal-cell carcinoma. Case report: We describe a case of a young man diagnosed with papillary renal-cell carcinoma that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal-cell carcinoma patient.Concluding Remarks: Nivolumab is a promising drug in patients with metastatic papillary renal-cell carcinoma and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

  13. Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05 mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA project and identified 60% (402 of the downregulated and 74% (469 of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

  14. Insulin-like growth factor-1 signaling in renal cell carcinoma

    International Nuclear Information System (INIS)

    Tracz, Adam F.; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M.

    2016-01-01

    Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen-binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells

  15. Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma.

    Science.gov (United States)

    Nakanishi, Hiromi; Miyata, Yasuyoshi; Mochizuki, Yasushi; Yasuda, Takuji; Nakamura, Yuichiro; Araki, Kyohei; Sagara, Yuji; Matsuo, Tomohiro; Ohba, Kojiro; Sakai, Hideki

    2018-05-19

    The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index (PI), apoptotic index (AI), and microvessel density (MVD) were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multi-variate analyses (hazard ratio=1.41, 95% confidential interval=1.03-1.93, P=.031), and was significantly correlated with PI, AI, and MVD (r=.47; P <. 001, r=-.31, P<.001, and r=.40, P<.001, respectively). In conclusion, CD57+ cell, CD68+ cell, and mast cell played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis. Copyright © 2018. Published by Elsevier Inc.

  16. Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor size versus CT perfusion parameters.

    Science.gov (United States)

    Chen, Chao; Kang, Qinqin; Xu, Bing; Guo, Hairuo; Wei, Qiang; Wang, Tiegong; Ye, Hui; Wu, Xinhuai

    To compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC). Tumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed. High-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did. Tumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma.

    Science.gov (United States)

    Naito, Sei; Makhov, Peter; Astsaturov, Igor; Golovine, Konstantin; Tulin, Alexei; Kutikov, Alexander; Uzzo, Robert G; Kolenko, Vladimir M

    2017-04-25

    Treatment with tyrosine kinase inhibitors (TKIs) significantly improves survival of patients with renal cell carcinoma (RCC). However, about one-quarter of the RCC patients are primarily refractory to treatment with TKIs. We examined viability of RCC and endothelial cells treated with low-density lipoprotein (LDL) and/or TKIs. Next, we validated the potential role of PI3K/AKT signalling in LDL-mediated TKI resistance. Finally, we examined the effect of a high-fat/high-cholesterol diet on the response of RCC xenograft tumours to sunitinib. The addition of LDL cholesterol increases activation of PI3K/AKT signalling and compromises the antitumour efficacy of TKIs against RCC and endothelial cells. Furthermore, RCC xenograft tumours resist TKIs in mice fed a high-fat/high-cholesterol diet. The ability of renal tumours to maintain their cholesterol homoeostasis may be a critical component of TKI resistance in RCC patients.

  18. Cell kinetics of differentiation of Na+-dependent hexose transport in a cultured renal epithelial cell line

    International Nuclear Information System (INIS)

    Cook, J.S.; Weiss, E.R.

    1985-01-01

    Fully differentiated cells of the renal proximal tubule have the capability of taking up hexoses across their apical borders by transport coupled to the Na + -electrochemical gradient. This property is also found in postconfluent cultures of the cloned cell line LLC-PK 1 , a morphologically polarized line of renal cells. Postconfluent cells develop the Na + -dependent capacity to transport hexoses at their apical surface. This function is not observable during the growth phase of the cultures. To analyze the developmental process at the cellular level a method has been derived to separate transporting cells, expressing the differentiated function, from nontransporting cells. The method is based on the swelling of the cells accompanying the uptake of the nonmetabolizable glucose analog alpha methylglucoside. The swollen cells have a lower buoyant density than the undifferentiated cells and may be separated from them on density gradients. Analysis of the distribution of cells on such gradients shows that after the cells reach confluence the undifferentiated subpopulation is recruited onto the differentiation pathway with a rate constant of 0.2 per day, that 5 to 7 days are required for a cell to traverse this pathway to the fully differentiated state, and that once the maximum uptake capacity is achieved the cells do not develop further

  19. Exosome production and its regulation of EGFR during wound healing in renal tubular cells.

    Science.gov (United States)

    Zhou, Xiangjun; Zhang, Wei; Yao, Qisheng; Zhang, Hao; Dong, Guie; Zhang, Ming; Liu, Yutao; Chen, Jian-Kang; Dong, Zheng

    2017-06-01

    Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing. Copyright © 2017 the American Physiological Society.

  20. Nuclear localization of the CK2α-subunit correlates with poor prognosis in Clear Cell Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Guerra, Barbara; Oliván-Viguera, Aida

    2017-01-01

    Protein kinase CK2a, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell...... Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2a expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC). Also the kinase activity of CK2 was significantly increased in ccRCC compared to normal...... renal cortex. Nuclear protein expression of CK2a correlated in univariate analysis with poor Progression Free Survival (HR = 8.11, p = 0.016). Functional analyses (cell proliferation assay) revealed an inhibitory effect of Caki-2 cell growth following CK2 inhibition with CX-4945. Our results suggest...

  1. Interval scanning photomicrography of microbial cell populations.

    Science.gov (United States)

    Casida, L. E., Jr.

    1972-01-01

    A single reproducible area of the preparation in a fixed focal plane is photographically scanned at intervals during incubation. The procedure can be used for evaluating the aerobic or anaerobic growth of many microbial cells simultaneously within a population. In addition, the microscope is not restricted to the viewing of any one microculture preparation, since the slide cultures are incubated separately from the microscope.

  2. A POX on Renal Cancer Cells | Center for Cancer Research

    Science.gov (United States)

    Proline oxidase, or POX, is an enzyme responsible for metabolizing the amino acid proline. POX contributes to the regulation of cell death that occurs when cellular systems malfunction, a process called apoptosis. Previous studies have determined that levels of POX are reduced in several types of human cancer. Likewise, many cancer cells become resistant to apoptosis, suggesting a link between POX and cancer cell survival.

  3. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Christopher J. Ricketts

    2018-04-01

    Full Text Available Summary: Renal cell carcinoma (RCC is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas

  4. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    International Nuclear Information System (INIS)

    Hillman, Gilda G; Wang, Yu; Che, Mingxin; Raffoul, Julian J; Yudelev, Mark; Kucuk, Omer; Sarkar, Fazlul H

    2007-01-01

    We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more

  5. Surgical Management of Renal Cell Carcinoma Extending Into Venous System: A 20-Year Experience.

    Science.gov (United States)

    Xiao, X; Zhang, L; Chen, X; Cui, L; Zhu, H; Pang, D; Yang, Y; Wang, Q; Wang, M; Gao, C

    2017-11-01

    The purpose of this study is to report our 20-year experience with the surgical management of renal cell carcinoma extending into the inferior vena cava using a novel classification system. We retrospectively reviewed the data of 103 patients (69 males, 34 females, mean age: 52.9 ± 12.6 years) with renal cell carcinoma involving the venous system treated between 1993 and 2014. The inferior vena cava tumor thrombus was classified into five levels: 0 (renal vein, n = 12), 1 (infrahepatic, n = 33), 2a (low retrohepatic, n = 26), 2b (high retrohepatic, n = 19), and 3 (supradiaphragmatic, n = 13). Clinical data were summarized, and overall survival, cancer-specific survival, and disease-free survival were examined by Cox regression analysis. All patients underwent radical surgery. Complete resections of the renal tumor and thrombus were achieved in 101 patients (98.1%). Two intraoperative and one postoperative in-hospital deaths (2.9%) occurred. In total, 19 patients (18.8%) had a total of 29 postoperative complications. Mean follow-up time was 46 months (range, 1-239 months). The 5- and 10-year overall survival rates were 62.9% and 56.0%, respectively. Metastasis, rather than thrombus level, was a significant risk factor associated with overall survival (hazard ratio = 4.89, 95% confidence interval: 2.24-10.67, p system can be used to select the optimal surgical approach and method for patients with renal cell carcinoma and venous thrombus. Its use is associated with prolonged survival and relatively few complications. Metastasis is an independent risk factor of overall survival.

  6. Salubrious effect of C-phycocyanin against oxalate-mediated renal cell injury.

    Science.gov (United States)

    Farooq, Shukkur Muhammed; Asokan, Devarajan; Sakthivel, Ramasamy; Kalaiselvi, Periandavan; Varalakshmi, Palaninathan

    2004-10-01

    C-phycocyanin, a biliprotein pigment found in some blue green algae (Spirulina platensis) with nutritional and medicinal properties, was investigated for its efficacy on sodium oxalate-induced nephrotoxicity in experimentally induced urolithic rats. Male Wistar rats were divided into four groups. Hyperoxaluria was induced in two of these groups by intraperitoneal infusion of sodium oxalate (70 mg/kg), and a pretreatment of phycocyanin (100 mg/kg) as a single oral dosage was given to one of these groups by 1 h prior to sodium oxalate infusion challenges. The study also encompasses an untreated control group and a phycocyanin-alone treated drug control group. The extent of lipid peroxidation (LPO) was evaluated in terms of renal concentrations of MDA, conjugated diene and hydroperoxides. The following assay was performed in the renal tissue (a) antioxidant enzymes such as superoxide dismutase (SOD) and catalase, (b) glutathione metabolizing enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glucose 6-phosphate dehydrogenase (G6PD), (c) the low molecular weight antioxidants (GSH, vitamins E and C) and protein carbonyl content. The increased concentrations of MDA, conjugated diene and hydroperoxide (index of the lipid peroxidation) were controlled (P antioxidants were appreciably increased (P antioxidants. It was noticed that the activities of antioxidant enzymes and glutathione metabolizing enzymes were considerably stabilized in rats pretreated with phycocyanin. We suggest that phycocyanin protects the integrity of the renal cell by stabilizing the free radical mediated LPO and protein carbonyl, as well as low molecular weight antioxidants and antioxidant enzymes in renal cells. Thus, the present analysis reveals that the antioxidant nature of C-phycocyanin protects the renal cell against oxalate-induced injury and may be a nephroprotective agent.

  7. The Use of Fibrous, Supramolecular Membranes and Human Tubular Cells for Renal Epithelial Tissue Engineering : Towards a Suitable Membrane for a Bioartificial Kidney

    NARCIS (Netherlands)

    Dankers, Patricia Y. W.; Boomker, Jasper M.; Huizinga-van der Vlag, Ali; Smedts, Frank M. M.; Harmsen, Martin C.; van Luyn, Marja J. A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We

  8. The use of fibrous, supramolecular membranes and human tubular cells for renal epithelial tissue engineering: towards a suitable membrane for a bioartificial kidney,

    NARCIS (Netherlands)

    Dankers, P.Y.W.; Boomker, J.M.; Huizinga-van der Vlag, A.; Smedts, F.M.M.; Harmsen, M.C.; Luyn, van M.J.A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We

  9. A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma

    Science.gov (United States)

    Wei, Jin-Huan; Haddad, Ahmed; Wu, Kai-Jie; Zhao, Hong-Wei; Kapur, Payal; Zhang, Zhi-Ling; Zhao, Liang-Yun; Chen, Zhen-Hua; Zhou, Yun-Yun; Zhou, Jian-Cheng; Wang, Bin; Yu, Yan-Hong; Cai, Mu-Yan; Xie, Dan; Liao, Bing; Li, Cai-Xia; Li, Pei-Xing; Wang, Zong-Ren; Zhou, Fang-Jian; Shi, Lei; Liu, Qing-Zuo; Gao, Zhen-Li; He, Da-Lin; Chen, Wei; Hsieh, Jer-Tsong; Li, Quan-Zhen; Margulis, Vitaly; Luo, Jun-Hang

    2015-01-01

    Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system. PMID:26515236

  10. Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters

    Science.gov (United States)

    Wang, Hai-yi; Su, Zi-hua; Xu, Xiao; Sun, Zhi-peng; Duan, Fei-xue; Song, Yuan-yuan; Li, Lu; Wang, Ying-wei; Ma, Xin; Guo, Ai-tao; Ma, Lin; Ye, Hui-yi

    2016-01-01

    Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan–rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K trans & Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID:27380733

  11. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Yingchun Wang

    2015-01-01

    Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

  12. Targeting population heterogeneity for optimal cell factories

    DEFF Research Database (Denmark)

    Heins, Anna-Lena; Carlqvist, Magnus; Helmark, S.

    the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were constructed which enabled us to perform single cell level...... analysis, and thereby created the possibility to map population heterogeneity. A factorial design with pH, glucose concentration and oxygen level was performed in batch cultivations using the growth reporter strains to evaluate the effect of those environmental factors on heterogeneity level and amount......To achieve an efficient production process, it is essential to optimize both the strain and the cultivation conditions. Traditionally, a microbial population has been considered homogeneous in optimization studies of fermentation processes. However, research has shown that a typical microbial...

  13. Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

    DEFF Research Database (Denmark)

    Sørensen, Anne V.; Donskov, Frede; Hermann, Gregers G.

    2014-01-01

    AbstractAim To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). Methods All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between...

  14. Choroid plexus metastasis of renal-cell carcinoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Shigemori, Minoru; Shimamoto, Houtetsu; Noguchi, Shinji; Yoshitake, Yasuhiro; Sugita, Yasuo; Kuramoto, Shinken

    1987-10-01

    A rare case of the choroid plexus metastasis of renal-cell carcinoma is reported. A 58-year-old man was admitted on March 3, 1982, with complaints of mild headache and a transient attack of muscle weakness of the left upper extremity. He had undergone a left nephrectomy because of renal-cell carcinoma 2 years before this admission. A CT scan revealed a small mass in the right lateral ventricle that was markedly enhanced by the contrast medium. A carotid angiogram was normal, but a left vertebral angiogram showed a round tumor stain in the distal portion of the right posterior choroidal artery. To determine the nature of the tumor, it was successfully removed via the right frontal transventricular approach. The immediate recovery from the operation was uneventful, but the patient became semicomatose 6 hours later because of a large subdural hematoma over the left hemisphere. An emergency operation for clot removal and external decompression failed to improve the patient's status, and he died on the 3rd postoperative day. An histological examination of the tumor determined the diagnosis of clear-cell-type renal-cell carcinoma. The CT demonstration of choroid plexus metastasis is quite rare. To our knowledge, only two cases have been described.

  15. MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio [Okayama Univ. (Japan). Graduate School of Medicine and Dentistry

    2003-08-01

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

  16. MR imaging of renal cell carcinoma. Associations among signal intensity, tumor enhancement, and pathologic findings

    International Nuclear Information System (INIS)

    Yabuki, Takayuki; Togami, Izumi; Kitagawa, Takahiro; Sasai, Nobuya; Tsushima, Tomoyasu; Shirasaki, Yoshinori; Hiraki, Yoshio

    2003-01-01

    The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation. (author)

  17. Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects

    Directory of Open Access Journals (Sweden)

    Naoto Kuroda

    2016-05-01

    Full Text Available Succinate dehydrogenase (SDH-deficient renal cell carcinoma (RCC was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD. The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB , SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

  18. Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Ye, Xueting; Xie, Jing; Huang, Hang; Deng, Zhexian

    2018-01-01

    Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling. © 2018 The Author(s). Published by S. Karger AG, Basel.

  19. Renal cell carcinoma in India demonstrates early age of onset & a late stage of presentation

    Directory of Open Access Journals (Sweden)

    Shalini Agnihotri

    2014-01-01

    Full Text Available Background & objectives: Clinical spectrum of most of the diseases in developing countries is different from the west. Similarly whether renal cell carcinomas (RCC in a developing country like India is seen in the same spectrum in relation to the age at presentation as in the west is not described in the literature. This study was carried out to investigate the spectrum of RCC in India with regards to age of onset, stage at presentation and survival. Methods: Patients with renal tumour, treated between January 2000 to December 2012 in a tertiary care hospital in north India, were analyzed for age at presentation, clinical features and histopathological characteristics. Clinical diagnosis was made by contrast enhanced computerized tomography (CECT scans and/or magnetic resonance imaging (MRI. Renal masses diagnosed as angiomyolipoma, infective masses and hydatid cysts were excluded from the analysis. Impact of various age groups on gender, tumour size, TNM stage, Fuhrman grade, histopathological subtypes, lymph node, inferior vena cava (IVC involvement and survival was analyzed. Patients were grouped in five age groups i.e. ≤39, 40-49, 50-59, 60-69 and more than 70 yr of age. Results: Of the total 617 patients with 617 renal tumours (2 patients had bilateral tumours but only the larger tumour was considered clinically suspected as RCC, 586 had epithelial cell tumour and the remaining 31 had non epithelial cell tumour. The mean tumour size was 8.08±3.5 cm (median 7, range 1-25 cm. Tumour of less than 4 cm size was present in only 10.4 per cent patients. The mean age at diagnosis was 55.15±13.34 (median 56, range 14-91 yr years. A total of 30.03 per cent of renal tumours presented in patients younger than 50 yr of age. Though there was no difference in stage, Fuhrman′s grade, IVC involvement and lymph nodal spread among various age groups, younger patients had higher proportion of non clear cell RCC and only 48.59 per cent of them presented

  20. Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

    Science.gov (United States)

    Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

    2018-03-25

    To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

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

    Directory of Open Access Journals (Sweden)

    João R. Friedrisch

    2003-06-01

    Full Text Available Although sickle cell anemia and sickle cell disease produce a variety of functional renal abnormalities they uncommonly cause end stage renal failure. Renal transplantation has been a successful alternative for the treatment of the rare terminal chronic renal failure with outcomes comparable with non-sickle recipients. This approach, however, has not been often described on patients with renal failure associated with SC hemoglobinopathy. Here we report the outcomes of two patients with chronic renal failure due to SC hemoglobinopathies who underwent renal transplantation. At the time of the transplantation they were both severely anemic and had frequent vasoocclosive pain crises. Both patients evolved with good allograft function, near normal hematological parameters, and very rare pain crisis, thirteen and eight years after transplant. These cases illustrate that terminal renal failure due to SC hemoglobinopathy can be successfully managed by renal transplantation and satisfactory long-term results are achievable not only in terms of renal allograft function but also of their hematological condition.Embora a anemia falciforme e as síndromes falciformes freqüentemente causem várias alterações funcionais renais, não é comum a insuficiência renal terminal. Nestes casos, o transplante renal é uma alternativa que se acompanha de resultados comparáveis aos obtidos em receptores sem hemoglobinopatias. Esta estratégia terapêutica tem sido, no entanto, pouco relatada para portadores de hemoglobinopatia SC. Este relato descreve a evolução de dois pacientes portadores de hemoglobinopatia SC que foram submetidos ao transplante renal. No momento do transplante ambos apresentavam severa anemia e crises dolorosas freqüentes. Os pacientes evoluíram com boa função do enxerto, parâmetros hematológicos quase normais e praticamente assintomáticos do ponto de vista da hemoglobinopatia, treze e oito anos após o transplante. Estes casos ilustram

  2. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  3. Community nephrology: audit of screening for renal insufficiency in a high risk population.

    Science.gov (United States)

    Kissmeyer, L; Kong, C; Cohen, J; Unwin, R J; Woolfson, R G; Neild, G H

    1999-09-01

    The rate of acceptance onto dialysis programmes has doubled in the past 10 years and is steadily increasing. Early detection and treatment of renal failure slows the rate of progression. Is it feasible to screen for patients who are at increased risk of developing renal failure? We have audited primary care records of patients aged 50-75 years who have either hypertension or diabetes, and are therefore considered to be at high risk of developing renal insufficiency. Our aim was to see whether patients had had their blood pressure measured and urine tested for protein within 12 months, and plasma creatinine measured within 24 months. This was a retrospective study of case notes and computer records in 12 general practices from inner and greater London. A total of 16,855 patients were aged 50-75 years. From this age group, 2693 (15.5%) patients were identified as being either hypertensive or diabetic, or both. Of the 2561 records audited, 1359 (53.1%) contained a plasma creatinine measured within 24 months, and 11% of these (150) had a value > 125 micromol/l. This equates to a prevalence of renal insufficiency of > 110,000 patients per million in this group. Forty two patients (28%) had been referred to a nephrologist. Of records audited, 73% contained a blood pressure measurement and 29% contained a test for proteinuria within 12 months. There is a high prevalence of chronic renal insufficiency in hypertensive and diabetic patients. It is feasible to detect renal insufficiency at a primary care level, but an effective system will require computerized databases that code for age, ethnicity, measurement of blood pressure and renal function, as well as diagnoses.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. OBJECTIVE: To assess outcomes of 2L according to type...... of therapy and change in IMDC prognostic category. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined......% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03). CONCLUSIONS: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy...

  5. Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

    2014-07-15

    Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

  6. Squamous cell carcinoma of skin after 20 years of renal transplantation

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    J Poddar

    2017-01-01

    Full Text Available Solid organ transplant recipients are at high risk of developing malignancies due to the prolonged use of immunosuppressant drugs. Squamous cell carcinoma of skin can occur in these patients even after decades of organ transplant. A 45-year-old male underwent renal transplant for end-stage renal disease 23 years ago and was on immunosuppressive drugs since then. The patient was on regular follow-up. Three years back, he developed squamous cell carcinoma of both forearms and hands, which was treated with radiation therapy using 8 MeV electrons, by parallel opposed fields to a dose of 60 Gy/30 fractions. Complete response to treatment was achieved at 3 months posttreatment. The patient is currently on follow-up and asymptomatic for skin lesions. Hence, these patients require longer follow-up, active surveillance, and screening for early diagnosis and prompt treatment of the premalignant and malignant conditions.

  7. Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation.

    LENUS (Irish Health Repository)

    Curry, Sarah

    2012-02-01

    The 2004 World Health Organization classification includes the new entity "neuroblastoma-associated renal cell carcinoma." The pathogenetic link between these entities is unknown as yet. The patient reported herein developed renal cell carcinoma after anaplastic embryonal rhabdomyosarcoma, a previously unknown association. The 2nd malignancy developed very soon after the 1st one, prompting concern for inherent cancer predisposition rather than a therapy-induced 2nd malignancy. A variety of features raised suspicion for Tp53 mutation, and indeed a pathogenic germline Tp53 mutation was identified in this child, despite a negative family history for Li-Fraumeni syndrome. Consideration of underlying predisposition is advocated in the context of rapid evolution of 2nd childhood malignancy.

  8. Renal Cell Carcinoma of 4 cm or Less: An Appraisal of Its Clinical Presentation and Contemporary Surgical Management

    Directory of Open Access Journals (Sweden)

    Victor T.W. Lee

    2006-01-01

    Conclusion: A significant proportion of patients had incidental diagnosis of small renal cell carcinoma. Local control may be achieved with either radical or partial nephrectomy, with excellent survival expected.

  9. Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT)

    International Nuclear Information System (INIS)

    Gerstein, Johanna; Meyer, Andreas; Fruehauf, Joerg; Karstens, Johann H.; Bremer, Michael; Sykora, Karl-Walter

    2009-01-01

    Purpose: to retrospectively assess the incidence and time course of renal dysfunction in children (≤ 16 years) following total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Patients and methods: between 1986 and 2003, 92 children (median age, 11 years; range, 3-16 years) underwent TBI before allogeneic SCT. 43 of them had a minimum follow-up of 12 months (median, 51 months; range, 12-186 months) and were included into this analysis. Conditioning regimen included chemotherapy and fractionated TBI with 12 Gy (n = 26) or 11.1 Gy (n = 17). In one patient, renal dose was limited to 10 Gy by customized renal shielding due to known nephropathy prior to SCt. Renal dysfunction was defined as an increase of serum creatinine > 1.25 times the upper limit of age-dependent normal. Results: twelve children (28%) experienced an episode of renal dysfunction after a median of 2 months (range, 1-10 months) following SCT. In all but one patient renal dysfunction was transient and resolved after a median of 8 months (range, 3-16 months). One single patient developed persistent renal dysfunction with onset at 10 months after SCT. None of these patients required dialysis. The actuarial 3-year freedom from persistent renal toxicity for children surviving > 12 months after SCt was 97.3%. Conclusion: the incidence of persistent renal dysfunction after fractionated TBI with total doses ≤ 12 Gy was very low in this analysis. (orig.)

  10. Primary leiomyoma of ureter coexisting with renal cell carcinoma: A case report

    International Nuclear Information System (INIS)

    Baek, Seung Hwan; Kim, Hee Jin; Han, Hyun Young

    2014-01-01

    Mesenchymal origin of ureter tumors account for less than 3 percent of all primary ureteral tumors. Among mesenchymal tumors, primary leiomyoma of ureter is extremely rare. Here, we present a case of primary leiomyoma of ureter coexisting with renal cell carcinoma. When encountering well-defined homogeneously enhanced mass of ureter on computed tomography, radiologist should keep in mind that ureteral leiomyoma should be considered as differential diagnosis.

  11. Primary leiomyoma of ureter coexisting with renal cell carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Seung Hwan; Kim, Hee Jin; Han, Hyun Young [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)

    2014-12-15

    Mesenchymal origin of ureter tumors account for less than 3 percent of all primary ureteral tumors. Among mesenchymal tumors, primary leiomyoma of ureter is extremely rare. Here, we present a case of primary leiomyoma of ureter coexisting with renal cell carcinoma. When encountering well-defined homogeneously enhanced mass of ureter on computed tomography, radiologist should keep in mind that ureteral leiomyoma should be considered as differential diagnosis.

  12. Evaluation of oxidative stress status and antioxidant capacity in patients with renal cell carcinoma

    OpenAIRE

    Aldemir, Mustafa; Karaguzel, Ersagun; Okulu, Emrah; Gudeloglu, Ahmet; Ener, Kemal; Ozayar, Asim; Erel, Ozcan

    2015-01-01

    Introduction We evaluated and compared the serum oxidative stress and antioxidant enzymes in patients with renal cell carcinoma (RCC) and the control group. Material and methods The prospective study consisted of 97 patients with RCC (Group 1) and 80 age and sex matched healthy volunteers (Group 2). Group 1 and 2 were compared concerning serum mean total oxidant status (TOS), total antioxidant capacity (TAC), paraoxonase-1 (PON-1), arylesterase, total thiol, catalase (CAT), myeloperoxidase (M...

  13. An update on current management of advanced renal cell cancer, biomarkers, and future directions

    OpenAIRE

    Zhi, Wanqing Iris; Kim, Jenny J.

    2014-01-01

    In the past decade, metastatic renal cell carcinoma (mRCC) treatment underwent significant advancement that resulted in an unprecedented improvement in the prognosis of this disease. This review will provide an updated review of currently approved treatment options, namely antiangiogenic and immunotherapy, as well as treatment guideline recommended by the National Comprehensive Cancer Network (NCCN). We will summarize studies ongoing in determining prognostic and predictive biomarkers in maxi...

  14. Evaluating the safety and efficacy of axitinib in the treatment of advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Gunnarsson O

    2015-02-01

    Full Text Available Orvar Gunnarsson,1 Nicklas R Pfanzelter,2 Roger B Cohen,1 Stephen M Keefe1 1Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, 2Department of Medicine, Division of Hematology and Oncology, Rush University Medical Center, Chicago, IL, USA Abstract: Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor-α, and c-kit. Phase I studies demonstrated 5 mg twice daily as the recommended starting dose with notable effects seen in renal cell carcinoma, an observation confirmed in Phase II trials. The trial of comparative effectivess of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS was an international randomized Phase III study designed for registration purposes, compared axitinib to sunitinib. This trial randomized 723 patients with metastatic kidney cancer to axitinib or sunitinib in the second-line setting and demonstrated a median progression-free survival of 6.7 months for axitinib versus 4.7 months for sorafenib (P<0.0001. Clinical benefit was detected regardless of prior therapy, but no overall survival benefit has been observed. Axitinib is well tolerated without a significant effect on quality of life. The most common grade 3 toxicities are hypertension (16%, diarrhea (11%, and fatigue (11%, with other notable side effects being anorexia, nausea, hand–foot syndrome, and rash. Patients who developed diastolic blood pressure >90 mmHg were noted to have significantly longer median overall survival and overall response rates when compared to normotensive patients. Therefore, the manufacturer recommends escalating the twice-daily dose to 7 mg and 10 mg, as tolerated, if there is no significant increase in blood pressure on treatment. Currently, axitinib is approved for use in the second-line setting for patients with metastatic renal cell carcinoma. Research is ongoing in other disease

  15. The occult nature of intramedullary spinal cord metastases from renal cell carcinoma.

    LENUS (Irish Health Repository)

    Zakaria, Zaitun

    2012-01-01

    Renal cell carcinomas (RCC) are characterised by a tendency to metastasise widely, often while remaining occult. Intramedullary spinal cord metastases (ISCM) from RCC may be the presenting feature of the disease or present at any time in the disease course. This case report discusses an ISCM from RCC which became manifested at the time of resection of the primary tumour. We review the literature published on ISCM from RCC from 1990 to date comparing disease characteristics and presentations.

  16. Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Anna Czajka

    2016-12-01

    Full Text Available Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN, a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs and proximal tubular cells (HK-2 were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer. In normoglycemia, HK-2 had significantly lower basal, ATP-linked and maximal respiration rates, and lower reserve capacity compared to HMCs. Hyperglycemia caused a down-regulation of all respiratory parameters within 4 days in HK-2 but not in HMCs. After 8 days of hyperglycemia, down-regulation of respiratory parameters persisted in tubular cells with compensatory up-regulated glycolysis. HMCs had reduced maximal respiration and reserve capacity at 8 days, and by 12 days had compromised mitochondrial respiration despite which they did not enhance glycolysis. These data suggest that diabetes is likely to lead to a cellular deficit in ATP production in both cell types, although with different sensitivities, and this mechanism could significantly contribute to the cellular damage seen in the diabetic kidney. Prevention of diabetes induced damage to renal mitochondrial respiration may be a novel therapeutic approach for the prevention/treatment of DN.

  17. The role of radiation therapy in multimodality treatment for renal-cell cancer

    International Nuclear Information System (INIS)

    Semikoz, N.G.; Kudryashov, O.G.; Ponomar'ov, V.V.; Osipenkov, R.A.; Anyishchenko, A.O.; Kudryashova, S.M.

    2011-01-01

    The authors report the results of multimodality treatment for renal-cell cancer (pT any, N any, M0) using pre- operative large-fraction irradiation. Our findings demonstrate that radiation therapy does not aggravate the conditions for surgery and improves long-term results. The data about efficacy of multimodality treatment (palliative nephrectomy with radiation therapy) in patients with primary metastatic kidney cancer T any, N any, M1) are also reported.

  18. RESULTS OF CLINICAL TRIALS OF MEDICAL TREA TMENT OF RENAL CELL CARCINOMA IN 2014–2015

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2015-01-01

    Full Text Available Over the last decade there have been significant changes in the approaches to the drug treatment of renal cell carcinoma. In clinical practice, there was a group of targeted drugs, the purpose of which has increased the life expectancy of patients with advanced kidney cancer. The studies devoted to the study of the sequence of destination targeted agents, combinations, studies of new drugs and to identify prognostic factors, are held.

  19. Interventional Management of a Renal Cell Carcinoma by Radiofrequency Ablation with Tagging and Cooling

    International Nuclear Information System (INIS)

    Mahnken, Andreas H.; Penzkofer, Tobias; Bruners, Philipp; Gunther, Rolf W.; Brehmer, Bernhard

    2009-01-01

    Over the last few years, percutaneous radiofrequency (RF) ablation has been successfully established as a viable treatment modality for small peripheral renal cell carcinoma (RCC). This technique is limited by central tumor location and tumor size. We report the interventional management of a 5.3 cm mixed RCC with central and exophytic parts by combining the RF ablation with embolization, tagging, and retrograde, as well as anterograde cooling. The potential pitfalls of complex hybrid interventions for treating RCC are discussed

  20. Establishment of a large panel of patient-derived preclinical models of human renal cell carcinoma

    OpenAIRE

    Lang, Herv?; B?raud, Claire; Bethry, Audrey; Danilin, Sabrina; Lindner, V?ronique; Coquard, Catherine; Rothhut, Sylvie; Massfelder, Thierry

    2016-01-01

    The objective of the present work was to establish a large panel of preclinical models of human renal cell carcinoma (RCC) directly from patients, faithfully reproducing the biological features of the original tumor. RCC tissues (all stages/subtypes) were collected for 8 years from 336 patients undergoing surgery, xenografted subcutaneously in nude mice, and serially passaged into new mice up to 13 passages. Tissue samples from the primary tumor and tumors grown in mice through passages were ...

  1. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels. © 2015 International Federation for Cell Biology.

  2. Alveolar architecture of clear cell renal carcinomas (≤5.0 cm) show high attenuation on dynamic CT scanning

    International Nuclear Information System (INIS)

    Fujimoto, Hiroyuki; Wakao, Fumihiko; Moriyama, Noriyuki; Tobisu, Kenichi; Kakizoe, Tadao; Sakamoto, Michiie

    1999-01-01

    To establish the correlation between tumor appearance on CT and tumor histology in renal cell carcinomas. The density and attenuation patterns of 96 renal cell carcinomas, each ≤5 cm in greatest diameter, were studied by non-enhanced CT and early and late after bolus injection of contrast medium using dynamic CT. The density and attenuation patterns and pathological maps of each tumor were individually correlated. High attenuated areas were present in 72 of the 96 tumors on early enhanced dynamic CT scanning. All 72 high attenuated areas were of the clear cell renal cell carcinoma and had alveolar architecture. The remaining 24 tumors that did not demonstrate high attenuated foci on early enhanced scanning included three clear cell, nine granular cell, six papillary, five chromophobe and one collecting duct type. With respect to tumor architecture, all clear cell tumors of alveolar architecture demonstrated high attenuation on early enhanced scanning. Clear cell renal cell carcinomas of alveolar architecture show high attenuation on early enhanced dynamic CT scanning. A larger number of patients are indispensable to obtaining clear results. However, these findings seem to be an important clue to the diagnosis of renal cell carcinomas as having an alveolar structure. (author)

  3. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

    2007-01-01

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

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

    Directory of Open Access Journals (Sweden)

    Nicastri A.L.

    2002-01-01

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

  5. The radiologist's role in the management of papillary renal cell carcinoma.

    Science.gov (United States)

    Corral de la Calle, M Á; Encinas de la Iglesia, J; Martín López, M R; Fernández Pérez, G C; Águeda Del Bas, D S

    Papillary carcinoma is the second most common renal cell carcinoma. It has a better prognosis than the more frequent clear cell carcinoma, although this does not hold true for advanced cases, because no specific treatment exists. It presents as a circumscribed peripheral tumor (small and homogeneously solid or larger and cystic/hemorrhagic) or as an infiltrating lesion that invades the veins, which has a worse prognosis. Due to their low vascular density, papillary renal cell carcinomas enhance less than other renal tumors, and this facilitates their characterization. On computed tomography, they might not enhance conclusively, and in these cases they are impossible to distinguish from hyperattenuating cysts. Contrast-enhanced ultrasonography and magnetic resonance imaging are more sensitive for detecting vascularization. Other characteristics include a specific vascular pattern, hypointensity on T2-weighted images, restricted water diffusion, and increased signal intensity in opposed phase images. We discuss the genetic, histologic, clinical, and radiological aspects of these tumors in which radiologists play a fundamental role in management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Heck, Julia E. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); Moore, Lee E. [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Lee, Yuan-Chin A. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); McKay, James D. [International Agency for Research on Cancer, Lyon (France); Hung, Rayjean J. [Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON (Canada); Karami, Sara [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Gaborieau, Valérie [International Agency for Research on Cancer, Lyon (France); Szeszenia-Dabrowska, Neonila [Department of Epidemiology, Institute of Occupational Medicine, Lodz (Poland); Zaridze, David G. [Cancer Research Centre, Institute of Carcinogenesis, Moscow (Russian Federation); Mukeriya, Anush [Cancer Research Centre, Department of Epidemiology, Moscow (Russian Federation); Mates, Dana [Institute of Public Health, Bucharest (Romania); Foretova, Lenka [Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno (Czech Republic); Janout, Vladimir; Kollárová, Helena [Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc (Czech Republic); Bencko, Vladimir [First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic (Czech Republic); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Brennan, Paul [International Agency for Research on Cancer, Lyon (France); Chow, Wong-Ho [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Boffetta, Paolo, E-mail: paolo.boffetta@mssm.edu [International Prevention Research Institute, Lyon (France); Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY (United States)

    2012-02-20

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  7. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    International Nuclear Information System (INIS)

    Heck, Julia E.; Moore, Lee E.; Lee, Yuan-Chin A.; McKay, James D.; Hung, Rayjean J.; Karami, Sara; Gaborieau, Valérie; Szeszenia-Dabrowska, Neonila; Zaridze, David G.; Mukeriya, Anush; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Kollárová, Helena; Bencko, Vladimir; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Boffetta, Paolo

    2012-01-01

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  8. Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy

    Directory of Open Access Journals (Sweden)

    Bellesoeur A

    2017-09-01

    Full Text Available Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard Department of Medical Oncology, Hopital Cochin AP-HP, Paris, France Abstract: Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs targeting the vascular endothelial growth factor receptors (VEGFRs. Axitinib is an oral second-generation TKI and a potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell carcinoma (RCC patients has been studied in various settings and particularly as second-line treatment. In this setting, axitinib with clinically based dose escalation compared to sorafenib has demonstrated an improvement in progression-free survival in a randomized Phase III trial leading to US Food and Drug Administration approval. In the first-line setting, axitinib failed to demonstrate improved efficacy over sorafenib, but the field of RCC treatment is rapidly changing with novel TKIs as cabozantinib or the emergence of check point inhibitors as nivolumab and the place of axitinib in therapy is therefore challenged. In this review, we focus on axitinib pharmacological and clinical properties in RCC patients and discuss its place in the treatment of patients with RCC. Keywords: renal cell carcinoma, tyrosine kinase inhibitors, vascular endothelial growth factor, axitinib, pharmacology

  9. Long-term survival in an adolescent with widely metastatic renal cell carcinoma with rhabdoid features.

    Science.gov (United States)

    Ettinger, L J; Goodell, L A; Javidian, P; Hsieh, Y; Amenta, P

    2000-01-01

    Renal cell carcinoma is rarely seen in children and adolescents. Patients with widespread disease at diagnosis have a particularly poor survival rate. Currently, all known chemotherapy has been ineffective in improving the median survival in patients with advanced disease. A 13-year-old black boy with stage IV renal cell carcinoma with rhabdoid features is a long-term disease-free survivor after aggressive multiagent chemotherapy. After the initial evaluation and histologic diagnosis of renal cell carcinoma, the patient received three courses of an aggressive chemotherapy regimen consisting of vincristine, doxorubicin, cyclophosphamide with mesna uroprotection, granulocyte colony-stimulating factor and erythropoietin (Epogen). After an almost complete response, a radical nephrectomy was performed and results demonstrated a solitary small nodule with viable tumor. After surgery, he received floxuridine infusion for 14 days by circadian schedule at 28-day intervals for a total of 1 year. The patient is well and free of disease 5 years after initial presentation. The dramatic response to treatment and long-term disease-free survival of this patient suggest this chemotherapeutic approach warrants additional investigation.

  10. Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β.

    Science.gov (United States)

    Choi, Yun-Hee; McNally, Brian T; Igarashi, Peter

    2013-07-01

    Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

  11. Radiosensitization of renal cell carcinoma in vitro through the induction of autophagy

    International Nuclear Information System (INIS)

    Anbalagan, Selvakumar; Pires, Isabel M.; Blick, Christopher; Hill, Mark A.; Ferguson, David J.P.; Chan, Denise A.; Hammond, Ester M.

    2012-01-01

    Background and purpose: For patients diagnosed with advanced renal cell carcinoma (RCC), there are few therapeutic options. Radiation therapy is predominantly used to treat metastasis and has not proven effective in the adjuvant setting for renal cancer. Furthermore, RCC is resistant to standard cytotoxic chemotherapies. Targeted anti-angiogenics are the standard of care for RCC but are not curative. Newer agents, such as mTOR inhibitors and others that induce autophagy, have shown great promise for treating RCC. Here, we investigate the potential use of the small molecule STF-62247 to modulate radiation. Materials and methods: Using RCC cell lines, we evaluate sensitivity to radiation in addition to agents that induce autophagic cell death by clonogenic survival assays. Furthermore, these were also tested under physiological oxygen levels. Results: STF-62247 specifically induces autophagic cell death in cells that have lost VHL, an essential mutation in the development of RCC. Treatment with STF-62247 did not alter cell cycle progression but when combined with radiation increased cell killing under oxic and hypoxic/physiological conditions. Conclusions: This study highlights the possibility of combining targeted therapeutics such as STF-62247 or temsirolimus with radiation to reduce the reliance on partial or full nephrectomy and improve patient prognosis.

  12. Endothelial cell chimerism after renal transplantation and vascular rejection.

    NARCIS (Netherlands)

    Lagaaij, E.L.; Cramer-Knijnenburg, G.F.; Kemenade, F.J. van; Es, L.A. van; Bruijn, J.A.; Krieken, J.H.J.M. van

    2001-01-01

    BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ are believed to remain of donor origin after transplantation. We

  13. Ethnic variation of the histological subtypes of renal cell carcinoma ...

    African Journals Online (AJOL)

    E.V. Ezenwa

    The content of the data obtained included the ethnicity categorized as Chinese, Malays, Indians and others (Indonesians, Vietnamese and other minor groups). Other data collected included age, gender and the histological subtype categorized as clear cell, papillary, chromophobe, collecting duct and unclassified subtypes.

  14. CNPY2 promoted the proliferation of renal cell carcinoma cells and increased the expression of TP53

    International Nuclear Information System (INIS)

    Taniguchi, Hidefumi; Ito, Saya; Ueda, Takashi; Morioka, Yukako; Kayukawa, Naruhiro; Ueno, Akihisa; Nakagawa, Hideo; Fujihara, Atsuko; Ushijima, So; Kanazawa, Motohiro; Hongo, Fumiya; Ukimura, Osamu

    2017-01-01

    Renal cell carcinoma (RCC) is the most common type of kidney cancer. However, the mechanisms underlying the progression of the disease are not well understood. The data in this report suggest that canopy FGF signaling regulator 2 (CNPY2) is a promoter of RCC progression. We found that CNPY2 significantly promoted growth of RCC cells and upregulated TP53 gene expression. Although TP53 is widely known as a tumor suppressor, in RCC TP53 promoted tumor cell growth. A typical p53 target gene, CDKN1A, was upregulated by both p53 and CNPY2 in RCC cells, suggesting that CNPY2 increased the expression level of TP53. Consistent with these results, CNPY2 and TP53 expression levels were positively correlated in RCC patients. These findings suggested that CNPY2 promoted cancer cell growth in RCC through regulating TP53 gene expression. - Highlights: • CNPY2 promoted growth of renal cell carcinoma (RCC) cells. • TP53 expression levels were increased by CNPY2 in RCC cells. • Growth of RCC cells was promoted by TP53. • CNPY2 expression positively correlated with TP53 expression in RCC patients.

  15. Development of Na+-dependent hexose transport in cultured renal epithelial cells (LLC-PK1)

    International Nuclear Information System (INIS)

    Weiss, E.R.; Amsler, K.; Dawson, W.D.; Cook, J.S.

    1984-01-01

    A number of factors were explored to analyze how they interact to yield the increasing transport capacity in differentiating cell populations. These factors include the number of functional transporters in the population, the distribution of these transporters among the individual cells, the Na + chemical gradient, the transmembrane potential, the pathways and activities of these pathways for efflux of glucoside, and cell-cell coupling between accumulating and non-accumulating cells. 35 references, 9 figures, 2 tables

  16. Creatinine, arsenic metabolism, and renal function in an arsenic-exposed population in Bangladesh.

    Science.gov (United States)

    Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Neugut, Y Dana; Pilsner, J Richard; Levy, Diane; Ilievski, Vesna; Slavkovich, Vesna; Islam, Tariqul; Factor-Litvak, Pam; Graziano, Joseph H; Gamble, Mary V

    2014-01-01

    Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of this association is warranted. Our first objective for this paper was to examine the potential renal toxicity of As exposure in Bangladesh. Our second objective relates to examining whether the previously reported positive association between urinary creatinine (uCrn) and As methylation may be explained by renal function. We had hypothesized that these associations relate to supply and demand for s-adenosylmethionine, the methyl donor for both creatine synthesis and As methylation. Alternatively, renal function could influence both As and creatinine excretion, or the As metabolites may influence renal function, which in turn influences uCrn. We conducted a cross-sectional study (N = 478) of adults, composed of a sample recruited in 2001 and a sample recruited in 2003. We assessed renal function using plasma cystatin C, and calculated the estimated glomerular filtration rate (eGFR). Consistent with renal toxicity of As, log-uAs had a marginal inverse association with eGFR in the 2003 sample (b = -5.6, p = 0.07), however this association was not significant in the 2001 sample (b = -1.9, p = 0.24). Adjustment for eGFR did not alter the associations between uCrn and the %uAs metabolites, indicating that GFR does not explain these associations. Increased eGFR was associated with increased odds of having %uInAs >12.2% (2001: OR = 1.01, 95%CI (1.00,1.03); 2003: OR = 1.04, 95%CI (1.01,1.07)). In the 2003 sample only, there was a negative association between eGFR and %uDMA (b = -0.08, p = 0.02). These results may indicate differential effects of renal function on excretion of InAs and DMA. Alternatively, a certain methylation pattern, involving decreased %InAs and increased %DMA, may reduce renal function. Given that these studies were cross-sectional, we cannot distinguish between these two possibilities. Discrepancies between the samples

  17. Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010)

    Science.gov (United States)

    Achermann, Christof; Stenner, Frank; Rothschild, Sacha I.

    2016-01-01

    In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have