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  1. Renal cell carcinoma

    Science.gov (United States)

    ... lining of very small tubes (tubules) in the kidney. ... Kidney cancer; Hypernephroma; Adenocarcinoma of renal cells; Cancer - kidney ... Follow your provider's recommendations in the treatment of kidney disorders, especially those that may require dialysis.

  2. 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.)

  3. Renal cell cancer without a renal primary

    Directory of Open Access Journals (Sweden)

    Cumani B

    2010-03-01

    Full Text Available Abstract Renal cell carcinoma has been increasing in incidence over the past two decades. Men are affected more than women and metastatic disease at presentation occurs in up to one third of patients. Metastasis can occur to virtually any organ, and involvement of multiple organs is not uncommon. To date, no reports have been found of metastatic disease without a renal primary. We present a case of renal cell cancer initially presenting as a subcutaneous mass with subsequent pancreatic and parotid gland metastases in absence of a primary renal source.

  4. Renal cell carcinoma with melanin pigment

    Science.gov (United States)

    Shetty, Jayaprakash; Chandrika; Laxman, Prabhu

    2010-01-01

    The incidence of renal cell carcinoma has been steadily increasing. There are several morphological types of renal cell carcinoma. Recognizing histologic patterns of renal cell carcinoma is important for correct diagnosis and subsequent medical care for the patient. Melanotic tumors in the kidney are very rare. Here, we present an unusual case of renal cell carcinoma with melanin pigment. PMID:20877613

  5. 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.

  6. Renal Preservation Therapy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yichun Chiu

    2012-01-01

    Full Text Available Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC for 20 years. Nowadays partial nephrectomy (PN is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN. Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN and robot assisted laparoscopic partial nephrectomy (RPN. On the other hand, thermoablative therapy and cryoablation also play an important role in the renal preservation therapy to improve the patient procedural tolerance. Novel modalities, but limited to small number of patients, include high-intensity ultrasound (HIFU, radiosurgery, microwave therapy (MWT, laser interstitial thermal therapy (LITT, and pulsed cavitational ultrasound (PCU. Although initial results are encouraging, their real clinical roles are still under evaluation. On the other hand, active surveillance (AS has also been advocated by some for patients who are unfit for surgery. It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function.

  7. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... being treated. See Drugs Approved for Kidney (Renal Cell) Cancer for more information. Biologic therapy Biologic therapy is a treatment that uses ... called biotherapy or immunotherapy. The following types of biologic therapy are being used or ... Nivolumab : Nivolumab is a monoclonal antibody that boosts ...

  8. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ...

  9. 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.

  10. Immunotherapy of renal cell carcinoma.

    Science.gov (United States)

    Gouttefangeas, Cécile; Stenzl, Arnulf; Stevanović, Stefan; Rammensee, Hans-Georg

    2007-01-01

    Carcinomas of the kidney generally have a poor prognosis and respond minimally to classical radiotherapy or chemotherapy. Immunotherapy constitutes an interesting alternative to these established forms of treatment, and indeed, cytokine-based therapies have been used for many years, leading to favorable clinical responses in a small subset of patients. During the past few years, immunotherapeutical trials targeting renal cell tumor-associated antigens have also been reported, with diverse passive or active approaches using antibodies or aimed at activating tumor-directed T lymphocytes. The following review presents the results and the progress made in the field, including classical cytokine treatments, non-myeloablative stem cell transplantation and antigen specific-based trials, with special focus on T-cell studies. In consideration of the few specific molecular targets described so far for this tumor entity, current strategies which can lead to the identification of new relevant antigens will be discussed. Hopefully these will very soon contribute to an improvement in renal cell carcinoma specific immunotherapy and its evaluation.

  11. 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...

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

    African Journals Online (AJOL)

    We describe a 22-year old female who presented with a 5-year history of a palpable, painless mass in the right flank. Computerized tomography demonstrated a solid renal mass measuring 18 cm × 13 cm with peripheral calcification, areas of vascularity and necrosis. The appearance suggested renal cell carcinoma or ...

  13. 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.

  14. Metastatic choriocarcinoma presenting as advanced renal cell ...

    African Journals Online (AJOL)

    Choriocarcinoma is an aggressive tumour arising as a malignant transformation of the gestational trophoblastic disease or rarely from the germ cells in the ovary and from testicular mixed germ cell tumour. Renal involvement due to Choriocarcinoma is rare we report here one of such rare cases. A 26yr old woman presented ...

  15. Snail heterogeneity in clear cell renal cell carcinoma.

    Science.gov (United States)

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

    2016-03-08

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

  16. 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.)

  17. 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.

  18. Sunitinib for advanced renal cell cancer

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2008-03-01

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

  19. Contrast agents and renal cell apoptosis.

    Science.gov (United States)

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

    2008-10-01

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

  20. Treatment of localised renal cell carcinoma

    NARCIS (Netherlands)

    van Poppel, Hein; Becker, Frank; Cadeddu, Jeffrey A.; Gill, Inderbir S.; Janetschek, Gunther; Jewett, Michael A. S.; Laguna, M. Pilar; Marberger, Michael; Montorsi, Francesco; Polascik, Thomas J.; Ukimura, Osamu; Zhu, Gang

    2011-01-01

    The increasing incidence of localised renal cell carcinoma (RCC) over the last 3 decades and controversy over mortality rates have prompted reassessment of current treatment. To critically review the recent data on the management of localised RCC to arrive at a general consensus. A Medline search

  1. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... being treated. See Drugs Approved for Kidney (Renal Cell) Cancer for more information. Biologic therapy Biologic therapy is a treatment that uses ... called biotherapy or immunotherapy. The following types of biologic therapy are being used or ... Nivolumab : Nivolumab is a monoclonal antibody that boosts ...

  2. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... being treated. See Drugs Approved for Kidney (Renal Cell) Cancer for more information. Biologic therapy Biologic therapy is a treatment that uses ... called biotherapy or immunotherapy. The following types of biologic therapy are being used or ... Nivolumab : Nivolumab is a monoclonal antibody that boosts ...

  3. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... being treated. See Drugs Approved for Kidney (Renal Cell) Cancer for more information. Biologic therapy Biologic therapy is a treatment that uses ... called biotherapy or immunotherapy. The following types of biologic therapy are being used or ... Nivolumab : Nivolumab is a monoclonal antibody that boosts ...

  4. The cell biology of renal filtration

    Science.gov (United States)

    Quaggin, Susan E.

    2015-01-01

    The function of the kidney, filtering blood and concentrating metabolic waste into urine, takes place in an intricate and functionally elegant structure called the renal glomerulus. Normal glomerular function retains circulating cells and valuable macromolecular components of plasma in blood, resulting in urine with just trace amounts of proteins. Endothelial cells of glomerular capillaries, the podocytes wrapped around them, and the fused extracellular matrix these cells form altogether comprise the glomerular filtration barrier, a dynamic and highly selective filter that sieves on the basis of molecular size and electrical charge. Current understanding of the structural organization and the cellular and molecular basis of renal filtration draws from studies of human glomerular diseases and animal models of glomerular dysfunction. PMID:25918223

  5. Human renal tubular epithelial cells suppress alloreactive T cell proliferation.

    Science.gov (United States)

    Demmers, M W H J; Korevaar, S S; Roemeling-van Rhijn, M; van den Bosch, T P P; Hoogduijn, M J; Betjes, M G H; Weimar, W; Baan, C C; Rowshani, A T

    2015-03-01

    Renal tubular epithelial cells (TECs) are one of the main targets of alloreactive T cells during acute rejection. We hypothesize that TECs modulate the outcome of alloimmunity by executing immunosuppressive effects in order to dampen the local inflammation. We studied whether TECs possess immunosuppressive capacities and if indoleamine 2,3-dioxygenase (IDO) might play a role in suppressing T cell alloreactivity. Next, we studied the role of programmed death ligand 1 (PD-L1) and intercellular adhesion molecule-1 (ICAM-1 with regard to TEC-related immunomodulatory effects. CD3/CD28 and alloactivated peripheral blood mononuclear cells were co-cultured with activated TECs. We analysed CD4(+) and CD8(+) T cell proliferation and apoptosis in the absence or presence of IDO inhibitor 1-methyl-L-tryptophan (1-L-MT), anti-PD-L1 and anti-ICAM-1. Further, we examined whether inhibition of T cell proliferation was cell-cell contact-dependent. We found that TECs dose-dependently inhibited CD4(+) and CD8(+) T cell proliferation (Pcell proliferation was only partially restored or failed to restore using 1-L-MT. Activated TECs increased early and late apoptosis of proliferating CD4(+) and CD8(+) T cells; only CD4(+) T cell apoptosis was statistically affected by 1-L-MT. Transwell experiments revealed that TEC-mediated immunosuppression is cell-cell contact-dependent. We found that anti-ICAM-1 affected only CD4(+) T cell apoptosis and not T cell proliferation. Our data show that TECs suppress both CD4(+) and CD8(+) T cell proliferation contact dependently. Interestingly, inhibition of proliferation and enhancement of apoptosis of T cell subsets is differentially regulated by indoleamine 2,3-dioxygenase and ICAM-1, with no evidence for the involvement of PD-L1 in our system. © 2014 British Society for Immunology.

  6. 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.

  7. Thyroid Hormones as Renal Cell Cancer Regulators

    OpenAIRE

    Szyma?ski, ?ukasz; Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

    2016-01-01

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

  8. 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...

  9. 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

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Rombo, Roman

    2016-04-01

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

  12. Metastatic renal cell carcinoma without evidence of a renal primary

    Science.gov (United States)

    Costantino, Corey; Thomas, George V.; Ryan, Christopher; Coakley, Fergus V.; Troxell, Megan L.

    2016-01-01

    Purpose Metastatic renal cell carcinoma (RCC), without an identified kidney primary, has been reported rarely. We report a patient with RCC metastatic to bilateral adrenal glands and liver, without an apparent renal primary. We detail the immunohistochemical and molecular studies employed to substantiate the diagnosis of RCC and direct therapy. Methods Histopathologic findings were correlated with imaging data and supplemented by a panel of immunohistochemical stains, as well as tumor sequence analysis. Results Despite the presence of bilateral adrenal masses and lack of tumor within kidney parenchyma, the diagnosis of RCC was substantiated by immunohistochemistry (RCC+/PAX2+/PAX8+/Melan-A−/SF-1− among others) and molecular genetic analysis, harboring mutations in VHL, TP53, KDM5C, and PBRM1. After debulking surgery, based on the diagnosis of RCC and the molecular profile, the patient was treated with a tyrosine kinase inhibitor (sunitinib), resulting in stablilization of disease. Conclusions This case illustrates the role of mutational analysis in carcinomas with rare or unusual presentations, such as metastatic RCC without a renal primary. PMID:26527083

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

    Science.gov (United States)

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

    2013-04-01

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

  14. 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

  15. MCPIP1 contributes to clear cell renal cell carcinomas development.

    Science.gov (United States)

    Ligeza, Janusz; Marona, Paulina; Gach, Natalia; Lipert, Barbara; Miekus, Katarzyna; Wilk, Waclaw; Jaszczynski, Janusz; Stelmach, Andrzej; Loboda, Agnieszka; Dulak, Jozef; Branicki, Wojciech; Rys, Janusz; Jura, Jolanta

    2017-08-01

    Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development.

  16. 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.

  17. 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)

  18. 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

  19. Endothelial protein C receptor in renal tubular epithelial cells and ...

    African Journals Online (AJOL)

    This study aims to investigate EPCR expression in renal tubular epithelial cells and related influencing factors. EPCR expression was assessed by flow cytometry in renal tubular epithelial cells. The effects of some reagents (high glucose, tumor necrosis factor–α and interleukin-1β) were measured by RT-PCR. The results ...

  20. Renal disease, epidermal necrosis, and epithelial cell antibodies.

    OpenAIRE

    Deal, J E; Groves, R W; Harmer, A W; Welsh, K I; MacDonald, D M; Rigden, S P

    1991-01-01

    OBJECTIVE--To describe the association between epithelial cell IgM, which has previously been associated with an increased incidence of loss of renal graft in children, with a novel cutaneous eruption and unexplained native renal disease. DESIGN--Observational study on children with epithelial cell antibody presenting with unexplained renal or skin disease. SETTING--General paediatric department and regional paediatric nephrology unit. PATIENTS--Six children (five girls, one boy), who present...

  1. Metabolic alterations in renal cell carcinoma.

    Science.gov (United States)

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

    2015-11-01

    Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Current MR imaging of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-15

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

  4. A case of metastatic renal cell carcinoma to thyroid gland.

    Science.gov (United States)

    Lee, Jae-Geun; Yang, Youngro; Kim, Kwang Sik; Hyun, Chang Lim; Lee, Ji Shin; Koh, Gwanpyo; Lee, Daeho

    2011-08-01

    Metastasis to the thyroid gland from distant cancer is rare, and, in some cases, is a diagnostic challenge. Here, we report a case of metastatic renal cell carcinoma of the thyroid gland. A 77-year-old man presented with a neck mass detected about 1 month previously. He had undergone a right nephrectomy owing to renal cell carcinoma 14 years previously. Fine needle aspiration cytology showed a few atypical follicular cells with nuclear atypia. Under a tentative diagnosis of papillary thyroid carcinoma, a total thyroidectomy was performed. The histologic and immunohistochemical studies of the surgical specimens indicated that the thyroid masses were metastatic renal cell carcinoma to the thyroid.

  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...... for tubulointerstitial mononuclear cell infiltration than patients without apoptotic tubular cells in their biopsies (P = 0.01). Furthermore, the level of tubular cell apoptosis displayed a statistically significant, positive correlation with the activity index score for mononuclear cell infiltration (r(s) = 0.472, P...... = 0.004) but not with scores for other activity or chronicity index components. These observations indicate that the degree of tubular cell apoptosis correlates with the severity of tubulointerstitial inflammation in SLE-associated nephritis. However, our findings do not suggest that apoptotic renal...

  6. Positive Captopril Renography Without Renal Artery Stenosis but a Renal Cell Carcinoma.

    Science.gov (United States)

    Hsieh, Ping-Ju; Kuo, Yen-Shu; Chen, Meng-Lin; Lin, Ching-Ling; Su, Hung-Yi

    2017-11-01

    A positive captopril renography indicates that patient's hypertension is renin dependent, most commonly caused by renal artery stenosis. The authors reported a case of positive captopril renography; however, CT demonstrated that renal arteries were intact, but there was a huge chromophobe renal cell carcinoma. Renin-dependent hypertension was relieved soon after nephrectomy. It is an uncommon cause of positive captopril renography.

  7. Intraventricular metastatic clear cell renal carcinoma.

    Science.gov (United States)

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

    2013-01-01

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

  8. A Case of Metastatic Renal Cell Carcinoma to Thyroid Gland

    OpenAIRE

    Lee, Jae-Geun; Yang, Youngro; Kim, Kwang Sik; Hyun, Chang Lim; Lee, Ji Shin; Koh, Gwanpyo; Lee, Daeho

    2011-01-01

    Metastasis to the thyroid gland from distant cancer is rare, and, in some cases, is a diagnostic challenge. Here, we report a case of metastatic renal cell carcinoma of the thyroid gland. A 77-year-old man presented with a neck mass detected about 1 month previously. He had undergone a right nephrectomy owing to renal cell carcinoma 14 years previously. Fine needle aspiration cytology showed a few atypical follicular cells with nuclear atypia. Under a tentative diagnosis of papillary thyroid ...

  9. Renal cell carcinoma in a horseshoe kidney and preoperative superselective renal artery embolization: a case report

    International Nuclear Information System (INIS)

    Kim, Tae Hoon

    2005-01-01

    Only rarely is renal cell carcinoma encountered in a horseshoe kidney. This is a case report on renal cell carcinoma in a horseshoe kidney, in which superselective renal artery embolization was performed preoperatively. CT and digital subtraction angiography revealed a horseshoe kidney with a 3-cm tumor in the left side. Superselective renal artery embolization of the tumor was performed as a prerequisite procedure for the organ-preserving surgery of simple enucleation. Preoperative superselective renal artery embolization can be an effective tool to facilitate organ-preserving surgery in a horseshoe kidney

  10. Urea selectively induces DNA synthesis in renal epithelial cells.

    Science.gov (United States)

    Cohen, D M; Gullans, S R

    1993-04-01

    Hyperosmotic stress with the functionally impermeant solute NaCl has been shown by us and others to inhibit cell growth and DNA synthesis. Several lines of evidence suggest that urea, the other principal renal medullary solute, may exert a growth-promoting effect on renal epithelial cells. Among these is the finding that urea upregulates expression at the mRNA level of two growth-associated immediate-early genes, Egr-1 and c-fos. In the present study, urea, in concentrations characteristic of the renal medulla, increased [3H]thymidine incorporation approximately threefold in confluent, growth-suppressed Madin-Darby canine kidney (MDCK) cells, whereas another readily membrane-permeant solute, glycerol, did not. Urea also overcame the inhibitory effect of hyperosmotic NaCl on DNA synthesis. The urea-induced increase in [3H]thymidine incorporation was also evident in the renal epithelial LLC-PK1 cell line, but not in renal nonepithelial and epithelial nonrenal cell types examined. In addition, it was associated with a 15% increase in total DNA content measured fluorometrically at 24 h of treatment. There was, however, no associated increase in cell proliferation as measured by cell number, total protein content, or cell cycle distribution. Urea also failed to induce polyploidy or aneuploidy. Therefore cells of renal epithelial origin may be uniquely capable of responding to hyperosmotic urea with increased DNA synthesis through an undefined and potentially novel mechanism.

  11. 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

  12. 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.).

  13. 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

  14. 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.

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

    Science.gov (United States)

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

    2012-11-01

    A better understanding of the molecular mechanisms of renal cell carcinogenesis could contribute to a decrease in the mortality rate of this disease. The aim of this study was to evaluate the glycosaminoglycans profile and heparanase expression in renal cell carcinoma. The study included 24 patients submitted to nephrectomy with confirmed pathological diagnosis of renal cell carcinoma. The majority of the samples (87.5%) were classified in the initial stage of renal cell carcinoma (clinical stages I and II). Heparanase messenger ribonucleic acid expression was evaluated by quantitative real-time reverse transcription polymerase chain reaction, and sulfated glycosaminoglycans were identified and quantified by agarose gel electrophoresis of renal cell carcinoma samples or non-neoplastic tissues obtained from the same patients (control group). The sulfated glycosaminoglycans and hyaluronic acid were analyzed in urine samples of the patients before and after surgery. The data showed a significant statistical increase in chondroitin sulfate, and a decrease in heparan sulfate and dermatan sulfate present in neoplastic tissues compared with non-neoplastic tissues. Higher heparanase messenger ribonucleic acid expression in the neoplastic tissues was also shown, compared with the non-neoplastic tissues. The urine glycosaminoglycans profile showed no significant difference between renal cell carcinoma and control samples. Extracellular matrix changes observed in the present study clarify that heparanase is possibly involved with heparan sulfate turnover, and that heparanase and the glycosaminoglycans can modulate initial events of renal cell carcinoma development. © 2012 The Japanese Urological Association.

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

    Directory of Open Access Journals (Sweden)

    Katarzyna Kluzek

    2015-05-01

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

  17. 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....

  18. 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)

  19. Metastatic renal cell carcinoma to the thyroid gland.

    Science.gov (United States)

    Duggal, Neal Murari; Horattas, Mark C

    2008-11-01

    To examine the presentation, diagnosis, and appropriate management of renal clear cell carcinoma metastasis to the thyroid gland. We describe a clinical case of solitary thyroid metastasis from renal clear cell carcinoma and present a comprehensive review of the related English-language literature. Common patterns of presentation and generalized overall management recommendations are evaluated and summarized. Eight years after nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid mass. Cytology and histopathologic surgical findings were consistent with a solitary metastasis most compatible with metastatic clear cell carcinoma from his previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the patient remains disease-free 5 years later. Although uncommon, nearly 150 cases of clinically recognized metastatic renal cell carcinoma to the thyroid have been reported in the English-language literature. Metastatic disease from the kidney to the thyroid gland can occur more than 20 years after nephrectomy with the average time interval being 7.5 years. Obtaining a full clinical history in any patient who presents with a thyroid nodule is essential to allow consideration of possible metastatic disease from previous primary tumor. Metastatic disease to the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal cancer is limited to the thyroid gland only, prompt, appropriate surgical intervention can be curative. Metastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of renal cell carcinoma.

  20. A Novel Protein Is Lower Expressed in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ruili Guan

    2014-04-01

    Full Text Available Engrailed-2 (EN2 has been identified as a candidate oncogene in breast cancer and prostate cancer. It is usually recognized as a mainly nuclear staining in the cells. However, recent studies showed a cytoplasmic staining occurred in prostate cancer, bladder cancer and clear cell renal cell carcinoma. The inconsistency makes us confused. To clarify the localization and expression of EN2 in renal cell carcinoma, anti-EN2 antibody (ab28731 and anti-EN2 antibody (MAB2600 were used for immunohistochemistry (IHC respectively. Interestingly, we found that EN2 detected by ab28731 was mainly presented in cytoplasm while EN2 detected by MAB2600 was mainly presented in nucleus. To further investigate the different patterns observed above, lysates from full-length EN2 over expression in HEK293T cells were used to identify which antibody the EN2 molecule bound by western blot. Results showed ab28731 did not react with the lysates. For this reason, the novel specific protein detected by ab28731 was not the EN2 molecule and was named nonEN2. Then using the renal carcinoma tissue microarray and renal tissues, we found that the protein expression levels of nonEN2 in kidney tumor tissues was significantly lower than that in kidney normal tissues (p < 0.05, so was in renal cell lines. Taken together, nonEN2 is lower expressed and may play an important role in renal cell carcinoma.

  1. Complete response of metastatic renal cancer with dendritic cell vaccine

    Directory of Open Access Journals (Sweden)

    Dall'Oglio Marcos

    2003-01-01

    Full Text Available INTRODUCTION: We report a case of metastatic renal cell carcinoma that presented involution following therapy with dendritic cells. CASE REPORT: Male, 51-year old patient underwent left radical nephrectomy in September 1999 due to renal cell carcinoma, evolved with recurrence of the neoplasia in January 2002, confirmed by resection of the lesion. A vaccine therapy based on dendritic cells was then performed during 5 months (4 applications. After this period, there was occurrence of new lesions, whose resection revealed areas of necrosis and inflammatory infiltrate. DISCUSSION: The outcome of renal cell carcinoma is influenced by prognostic factors that confer more aggressive tumor characteristics. However, in cases of recurrence, the systemic therapy with dendritic cells-based vaccine can be associated with a better outcome with regression of disease.

  2. Synchronous presentation of nasopharyngeal and renal cell carcinomas

    OpenAIRE

    Boruban,Cem; Yavas,Ozlem; Altundag,Kadri; Sencan,Orhan

    2006-01-01

    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 re...

  3. Expression of parafibromin in major renal cell tumors

    Directory of Open Access Journals (Sweden)

    C. Cui

    2012-10-01

    Full Text Available Parafibromin, encoded by HRPT2 gene, is a recently identified tumor suppressor. Complete and partial loss of its expression have been observed in hyperparathyroidism-jaw tumor (HPT-JT, parathyroid carcinoma, breast carcinoma, lung carcinoma, gastric and colorectal carcinoma. However, little has been known about its expression in renal tumors. In order to study the expression of parafibromin in a series of the 4 major renal cell tumors - clear cell renal cell carcinoma (ccRCC, papillary renal cell carcinoma (pRCC, chromophobe renal cell carcinoma (chRCC and oncocytoma. One hundred thirty nine renal tumors including 61 ccRCCs, 37 pRCCs, 22 chRCCs and 19 oncocytomas were retrieved and used for the construction of renal tissue microarrays (TMAs. The expression of parafibromin was detected by immunohistochemical method on the constructed TMAs. Positive parafibromin stains are seen in 4 out of 61 ccRCCs (7%, 7 out of 37 pRCCs (19%, 12 out of 23 chRCCs (52% and all 19 oncocytomas (100%. Parafibromin expression varies significantly (P< 8.8 x10-16 among the four major renal cell tumors and were correlated closely with tumor types. No correlation of parafibromin expression with tumor staging in ccRCCs, pRCCs and chRCCs, and Fuhrman nuclear grading in ccRCCs and pRCCs. In summary, parafibromin expression was strongly correlated with tumor types, which may suggest that it plays a role in the tumorigenesis in renal cell tumors.

  4. 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.

  5. 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 ...

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

    African Journals Online (AJOL)

    M.M. Gargouri

    2016-08-21

    Aug 21, 2016 ... Abstract. 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 ...

  7. 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.

  8. MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration.

    Science.gov (United States)

    Zhu, Jie; Cui, Liang; Xu, Axiang; Yin, Xiaotao; Li, Fanglong; Gao, Jiangping

    2017-03-07

    Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design. MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1. MEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells. By investigating the role of MEIS1 in ccRCC cells' survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (cc

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

    Directory of Open Access Journals (Sweden)

    Lipworth Loren

    2011-04-01

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

  10. Choroidal metastasis from renal cell carcinoma presenting with cataract

    International Nuclear Information System (INIS)

    Shoaib, K.K.; Haq, I.; Zafar, N.

    2008-01-01

    We report a case of rare involvement of the eye with choroidal metastasis from renal cell carcinoma presenting 08 years after the primary tumor was removed. The patient initially presented with cataract most probably induced by the tumor. After cataract extraction, tumor was detected when it induced vitreous involvement and retinal detachment. Enucleation was performed and an extraocular mass was also excised. Histopathology confirmed the diagnosis of metastasis from renal cell carcinoma in the ocular tumor, extraocular mass and the vitreous. (author)

  11. Basosquamous Cell Carcinoma Developing from a Renal Transplantation Recipient

    Directory of Open Access Journals (Sweden)

    Akira Tsukada

    2012-10-01

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

  12. 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

  13. Repopulation of porcine kidney scaffold using porcine primary renal cells.

    Science.gov (United States)

    Abolbashari, Mehran; Agcaoili, Sigrid M; Lee, Mi-Kyung; Ko, In Kap; Aboushwareb, Tamer; Jackson, John D; Yoo, James J; Atala, Anthony

    2016-01-01

    The only definitive treatment for end stage renal disease is renal transplantation, however the current shortage of organ donors has resulted in a long list of patients awaiting transplant. Whole organ engineering based on decellularization/recellularization techniques has provided the possibility of creating engineered kidney constructs as an alternative to donor organ transplantation. Previous studies have demonstrated that small units of engineered kidney are able to maintain function in vivo. However, an engineered kidney with sufficient functional capacity to replace normal renal function has not yet been developed. One obstacle in the generation of such an organ is the development of effective cell seeding methods for robust colonization of engineered kidney scaffolds. We have developed cell culture methods that allow primary porcine renal cells to be efficiently expanded while maintaining normal renal phenotype. We have also established an effective cell seeding method for the repopulation of acellular porcine renal scaffolds. Histological and immunohistochemical analyses demonstrate that a majority of the expanded cells are proximal tubular cells, and the seeded cells formed tubule-like structures that express normal renal tubule phenotypic markers. Functional analysis revealed that cells within the kidney construct demonstrated normal renal functions such as re-adsorption of sodium and protein, hydrolase activity, and production of erythropoietin. These structural and functional outcomes suggest that engineered kidney scaffolds may offer an alternative to donor organ transplant. Kidney transplantation is the only definitive treatment for end stage renal disease, however the current shortage of organ donors has limited the treatment. Whole organ engineering based on decellularization/recellularization techniques has provided the possibility of creating engineered kidney constructs as an alternative to donor organ transplantation. While previous studies have

  14. 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.

  15. 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

  16. 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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  18. Apoptotic tubular cell death during acute renal allograft rejection

    NARCIS (Netherlands)

    Wever, P. C.; Aten, J.; Rentenaar, R. J.; Hack, C. E.; Koopman, G.; Weening, J. J.; ten Berge, I. J.

    1998-01-01

    Tubular cells are important targets during acute renal allograft rejection and induction of apoptosis might be a mechanism of tubular cell destruction. Susceptibility to induction of apoptosis is regulated by the homologous Bcl-2 and Bax proteins. Expression of Bcl-2 and Bax is regulated by p53,

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

    Science.gov (United States)

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

    2009-11-01

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

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

    Science.gov (United States)

    Maeshima, Akito; Nakasatomi, Masao; Nojima, Yoshihisa

    2014-01-01

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

  2. Computed tomographic evaluation of the renal vein and inferior vena cava in renal cell carcinoma

    International Nuclear Information System (INIS)

    Masuda, Fujio; Nakada, Gyojiro; Onishi, Tetsuo; Higashi, Yoichiro; Machida, Toyohei

    1980-01-01

    Renal cell carcinoma not rarely invades the renal vein and inferior vena cava with formation of tumor thrombus. On the other hand, congenital anomalies of these venous channels are occasionally encountered. At the time of surgery of renal cell carcinoma, therefore, preoperative evaluation of the renal vein and inferior vena cava is desirable. In 22 cases of renal cell carcinoma treated at the Jikei University Hospital during 16 months period from Jan. 1979 to apr. 1980, the ranal vein and inferior vena cava were examined by computed tomography (CT). Intravenous tumor thrombus was diagnosed in 4, double inferior vena cava in one and retroaortic left renal vein in one. All these CT diagnosis were confirmed to be correct by surgery. Three of tumor thrombus cases showed involvement of inferior vena cava. CT findings included dilated vein in 4 and filling defect after contrast enhancement in 2. In double inferior vena cava, CT at the level of the upper pole of kidney showed the left inferior vena cava traversing in front of the aorta and conjoining the left inferior vena cava, CT at the level of renal vein the left renal vein draining into the left inferior vena cava and CT at the lower level two round inferior vena cava with the aorta between them. It was a diagnostically useful finding that the left inferior vena cava was markedly stained in CT after contrast enhancement jestas the aorta and the right inferior vena cava. In retroaortic left renal vein, CT showed the left renal vein running behind the aorta and draining into the inferior vena cava. Preoperative information on congenital anomalies of the renal vein and inferior vena cava or tumor thrombus and its extension are very important particularly for radical surgery to be conducted safely without postoperative complications. Computed tomography is quite useful in evaluation of morbid state of the renal vein and inferior vena cava. (author)

  3. Immunotherapy for metastatic renal cell carcinoma.

    Science.gov (United States)

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

    2017-05-15

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

  4. 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.

  5. 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......%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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...

  11. Metastatic Clear Cell Renal Cell Carcinoma Presenting with a Gingival Metastasis

    OpenAIRE

    Ali, Rusha A.E.; Mohamed, Kamal E.H.

    2016-01-01

    Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation...

  12. Human renal adipose tissue induces the invasion and progression of renal cell carcinoma

    Science.gov (United States)

    Campo-Verde-Arbocco, Fiorella; López-Laur, José D.; Romeo, Leonardo R.; Giorlando, Noelia; Bruna, Flavia A.; Contador, David E.; López-Fontana, Gastón; Santiano, Flavia E.; Sasso, Corina V.; Zyla, Leila E.; López-Fontana, Constanza M.; Calvo, Juan C.; Carón, Rubén W.; Creydt, Virginia Pistone

    2017-01-01

    We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease. PMID:29212223

  13. BHD Tumor Cell Line and Renal Cell Carcinoma Line | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Scientists at the National Cancer Institute  have developed a novel renal cell carcinoma (RCC) cell line designated UOK257, which was derived from the surgical kidney tissue of a patient with hereditary Birt-Hogg-Dube''''(BHD) syndrome and companion cell line UOK257-2 in which FLCN expression has been restored by lentivirus infection. The NCI Urologic Oncology Branch seeks parties interested in licensing or collaborative research to co-develop, evaluate, or commercialize kidney cancer tumor cell lines.

  14. Cardiac Metastasis in Renal Cell Carcinoma

    African Journals Online (AJOL)

    abp

    2015-10-21

    Oct 21, 2015 ... following: pleural mesothelioma (48.4%), melanoma (27.8%), lung adenocarcinoma (21%), undifferentiated carcinomas (19.5%), lung squamous cell carcinoma (18.2%) and breast carcinoma (15.5%). High rates of heart metastatisation have also been observed in patients affected by ovarian carcinoma ...

  15. Tumor Enucleation for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Zachary L Smith

    2015-03-01

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

  16. Renal response assayed by survival of tubule epithelial cells

    International Nuclear Information System (INIS)

    Withers, H.R.; Mason, K.A.

    1985-01-01

    The epithelium of the renal tubules is essentially non-proliferative and hence is slow to be depleted after irradiation. Ultimately, however, depletion occurs. If cells survive within a tubule they regenerate the epithelial lining. After higher doses, e.g. greater than 12 Gy, some tubules are completely depopulated of epithelium giving rise to a histological picture of empty tubules interspersed with regenerated tubules. It is assumed that nephrons are all essentially the same size, that cell survival is a random probability and that, therefore, when a proportion of tubules are completely devoid of epithelium, those that aren't have regenerated from one or a few cells, the distribution of numbers of survivors per tubule following Poisson statistics. Based on these assumptions it is possible to determine a dose-survival relationship for renal tubule cells

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

    DEFF Research Database (Denmark)

    Wells, J Connor; Stukalin, Igor; Norton, Craig

    2017-01-01

    BACKGROUND: 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. OBJECTIVE...... 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. RESULTS AND LIMITATIONS: Everolimus was the most prevalent third...

  18. Intravenous Renal Cell Transplantation for Polycystic Kidney Disease

    Science.gov (United States)

    2014-06-01

    cells from a single donor, a critical point since many ESRD patients never get renal transplants due to shortage of organs for donation (13). The... Transplantation for Polycystic Kidney Disease PRINCIPAL INVESTIGATOR: Jesus H. Dominguez CONTRACTING ORGANIZATION : Indiana University School of...sections were examined under the fluorescent microscope to identify the location and number of transplanted cells in all the organs harvested. One half

  19. Downregulation of ABCD1 in human renal cell carcinoma.

    Science.gov (United States)

    Hour, Tzyh-Chyuan; Kuo, Yi-Zih; Liu, Guang-Yan; Kang, Wang-Yi; Huang, Chao-Yuan; Tsai, Yu-Chieh; Wu, Wen-Jeng; Huang, Shu-Pin; Pu, Yeong-Shiau

    2009-01-01

    Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Delayed diagnosis may result in progression and metastasis. Markers for early detection of RCC are lacking. The ATP-binding cassette transporter D1 (ABCD1) is located in the human peroxisome membrane. Its mutation causes X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disorder affecting lipid storage. The role of ABCD1 in human renal tumorigenesis was unclear. In this study, three pairs of RCC tissues were examined by cDNA microarray and data suggested that ABCD1 mRNA is downregulated. Downregulation of ABCD1 expression was confirmed by real-time PCR. ABCD1 expression was also downregulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. ABCD1 mRNA and protein expression levels assessed by immunohistochemistry in the RCC tissues were similar between genders, tumor grades, and tumor stages. Immunohistochemical assays also showed that ABCD1 expression was significantly higher in normal than in cancerous tissues (pABCD1 downregulation may be involved in human renal tumorigenesis.

  20. Individualized medicine for renal cell carcinoma: establishment of primary cell line culture from surgical specimens.

    Science.gov (United States)

    Kim, Fernando J; Campagna, Adriano; Khandrika, Lakshmipathi; Koul, Sweaty; Byun, Seok-Soo; vanBokhoven, Adrie; Moore, Ernest E; Koul, Hari

    2008-10-01

    The lack of effective "in vivo" and "in vitro" models to predict success of pharmacological therapy for patients with renal cell carcinoma, as well as, the variety of cancer cell types demands the development of better experimental models to understand the pathophysiology of the disease and evaluate drug sensitivity in vitro. To develop primary renal cancer cell culture irrespective of tumor grade and tumor type, harvested from the patient's pathological specimen immediately after the laparoscopic radical nephrectomy to study potential "in vivo" pharmacological sensitivity. A total of 24 patients (17 males and 7 females). Mean age of 63.1+/-3.1 y.o. The mean size of the renal masses was 7.56+/-3.1 cm. Normal and pathological renal tissue was collected immediately after the specimen was extracted and submitted to enzymatic digestion for 16-24 hours. Clear cell carcinoma cells were selected through multiple passages in DMEM medium supplemented with glucose and antibiotics. Establishment of cell line culture from all the patients' specimens irrespective of tumor grade and tumor type was achieved successfully. In addition to the tumor cell line culture, normal parenchyma tissue yielded primary cell lines to allow testing the response of tumor types to various pharmacological therapeutic agents and toxicity of such treatments to healthy tissue. From the initial collection of the specimens obtained after the removal of the kidney to the development of cell lines took occurred in average 32+6 hrs. The cells in culture showed characteristics of epithelial cells; like expression on cytokeratin and were maintained in culture for more than 20 passages. The development of renal cancer cell cultures in vitro is labor intense but may yield a more realistic model to tailor pharmacological therapies and predict therapeutic success prior to "in vivo" application-a step in the direction of individualized medicine for RCC.

  1. Renal cell carcinoma in the first two decades of life

    International Nuclear Information System (INIS)

    Chan, H.S.L.

    1983-01-01

    Renal cell carcinoma occurs rarely in the first two decades of life. This paper reviews the clinical and radiographgic features of 17 such patients (10F:7M, mean age=12 years) seen in a 24 year period. The almost equal sex incidence contrasts with the male preponderance in adults. All patients presented with symptoms and signs referable to the primary lesion. In comparison to Wilms' tumor, renal cell carcinoma in childhood and adolescence usually presents with a smaller abdominal mass which is frequently not palpable or visible on plain abdominal radiographs. Ultrasound and CT showed non-specific solid intrarenal masses. This rare tumor of childhood should be included in the differential diagnosis of intrarenal mass lesions, particularly in older children with hematuria and renal calification on plain radiographs. One child in this series had tuberous sclerosis. The prognosis depends on the stage of disease at presentation. (orig.)

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

    African Journals Online (AJOL)

    İ. Ateş

    2015-10-09

    Oct 9, 2015 ... A Stauffer's syndrome variant associated with renal cell carcinoma and thrombocytopenia. ˙I. Ates∗. , M. Kaplan, N. Yılmaz. Ankara Numune Education and Research Hospital, Internal Medicine Clinic, Ankara, Turkey. Received 20 April 2015; received in revised form 22 May 2015; accepted 25 May 2015.

  3. Ethnic variation of the histological subtypes of renal cell carcinoma ...

    African Journals Online (AJOL)

    Introduction: The purpose of this study is to determine how the histological subtypes of renal cell carcinoma (RCC) vary among the heterogeneous Singaporean population and how this affects the survival rate. Patients and methods: The data analyzed in this retrospective study of the histological subtypes of RCC cases ...

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

    Directory of Open Access Journals (Sweden)

    Anna Scavuzzo

    2017-07-01

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

  5. 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...

  6. 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...

  7. Renal cell carcinoma in pregnancy: Still a management challenge

    African Journals Online (AJOL)

    I.C. Akpayak

    Abstract. Background: Renal cell carcinoma during pregnancy is uncommon. We present a rare case, highlighting the dilemma faced by the patient and the challenge of deciding the appropriate management option. Patient: A 28-year-old patient presented at 14 weeks of gestation with a 2-month history of left loin pain.

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

    African Journals Online (AJOL)

    Renal cell carcinoma is the most common cancer involving the kidneys. It is reported to occur in 3% of all malignancies in adults and accounts for 90 - 95% of all cancers involving the kidneys. The peak age of diagnosis is between 50 and 70 years; in recent years the median age has been given as 64. There is also a slight ...

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

    Directory of Open Access Journals (Sweden)

    Alvaro C Ucero

    2010-04-01

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

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

    Science.gov (United States)

    A, Sankin

    2016-01-01

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

  11. Alcoholic beverages and risk of renal cell cancer

    NARCIS (Netherlands)

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

    2007-01-01

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

  12. Adult renal cell carcinoma in Lagos: Experience and challenges at ...

    African Journals Online (AJOL)

    Abstract. Introduction: Renal cell carcinoma (RCC), regarded as the most lethal of all urological tumors, is relatively uncommon. Recent reports from developed countries indicate a rising incidence, most likely from the increasing availability of imaging services leading to an increase in incidental diagnosis of early stage.

  13. 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.

  14. Renal cell carcinoma in pregnancy: Still a management challenge

    African Journals Online (AJOL)

    I.C. Akpayak

    www.ees.elsevier.com/afju · www.sciencedirect.com. Short Communication. Renal cell carcinoma in pregnancy: Still a management challenge. I.C. Akpayak. ∗. , S.I. Shuiabu, C.G. Ofoha, N.K. Dakum, V.M. Ramyil. Urology Division, Surgery Department, Jos University Teaching Hospital, Jos, Nigeria. Received 14 June 2014 ...

  15. 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 ...

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

    Science.gov (United States)

    ... Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment (PDQ®)–Patient Version General Information About Transitional Cell Cancer of the Renal Pelvis and Ureter Go to Health Professional Version Key Points Transitional ...

  17. 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.

  18. Thyroid Metastasis in Pyramidal Lobe from Renal Cell Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hyung Seok; Kim, Dong Wook; Kim, Sang Su [Dept. of Radiology, Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of); Jung, Soo Jin [Dept. of Pathology, Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2011-06-15

    Thyroid metastasis is rare. The most common primary malignancy of thyroid metastasis worldwide is known to be renal cell carcinoma, but the most common primary malignancy in South Korea is breast cancer. Many studies have reported that primary renal cell carcinoma is almost unilateral and thyroid metastasis from renal cell carcinoma is a nearly ipsilateral, single lesion. We report a case of pyramidal lobe metastasis from renal cell carcinoma.

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

    OpenAIRE

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

    2016-01-01

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

  20. 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)

  1. 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.

  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. Concomitant tumor and autoantigen vaccination supports renal cell carcinoma rejection.

    Science.gov (United States)

    Herbert, Nicolás; Haferkamp, Axel; Schmitz-Winnenthal, Hubertus F; Zöller, Margot

    2010-07-15

    Efficient tumor vaccination frequently requires adjuvant. Concomitant induction of an autoimmune response is discussed as a means to strengthen a weak tumor Ag-specific response. We asked whether the efficacy of dendritic cell (DC) vaccination with the renal cell carcinoma Ags MAGE-A9 (MAGE9) and G250 could be strengthened by covaccination with the renal cell carcinoma autoantigen GOLGA4. BALB/c mice were vaccinated with DC loaded with MHC class I-binding peptides of MAGE9 or G250 or tumor lysate, which sufficed for rejection of low-dose RENCA-MAGE9 and RENCA-G250 tumor grafts, but only retarded tumor growth at 200 times the tumor dose at which 100% of animals will develop a tumor. Instead, 75-100% of mice prevaccinated concomitantly with Salmonella typhimurium transformed with GOLGA4 cDNA in a eukaryotic expression vector rejected 200 times the tumor dose at which 100% of animals will develop tumor. In a therapeutic setting, the survival rate increased from 20-40% by covaccination with S. typhimurium-GOLGA4. Autoantigen covaccination significantly strengthened tumor Ag-specific CD4(+) and CD8(+) T cell expansion, particularly in peptide-loaded DC-vaccinated mice. Covaccination was accompanied by an increase in inflammatory cytokines, boosted IL-12 and IFN-gamma expression, and promoted a high tumor Ag-specific CTL response. Concomitant autoantigen vaccination also supported CCR6, CXCR3, and CXCR4 upregulation and T cell recruitment into the tumor. It did not affect regulatory T cells, but slightly increased myeloid-derived suppressor cells. Thus, tumor cell eradication was efficiently strengthened by concomitant induction of an immune response against a tumor Ag and an autoantigen expressed by the tumor cell. Activation of autoantigen-specific Th cells strongly supports tumor-specific Th cells and thereby CTL activation.

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

    Science.gov (United States)

    Peces, R; Alvarez-Navascués, R

    2001-02-01

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

  5. Functional Kidney Bioengineering with Pluripotent Stem-Cell-Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds.

    Science.gov (United States)

    Du, Chan; Narayanan, Karthikeyan; Leong, Meng Fatt; Ibrahim, Mohammed Shahrudin; Chua, Ying Ping; Khoo, Vanessa Mei Hui; Wan, Andrew C A

    2016-08-01

    Recent advances in developmental biology and stem cell technology have led to the engineering of functional organs in a dish. However, the limited size of these organoids and absence of a large circulatory system poses limits to its clinical translation. To overcome these issues, decellularized whole kidney scaffolds with native microstructure and extracellular matrix (ECM) are employed for kidney bioengineering, using human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells. To demonstrate ECM-guided cellular assembly, the present work is focused on generating the functional unit of the kidney, the glomerulus. In the repopulated organ, the presence of endothelial cells broadly upregulates the expression level of genes related to renal development. When the cellularized native scaffolds are implanted in SCID mice, glomeruli assembly can be achieved by co-culture of the renal progenitors and endothelial cells. These individual glomerular units are shown to be functional in the context of the whole organ using a simulated bio-reactor set-up with urea and creatinine excretion and albumin reabsorption. Our results indicate that the repopulation of decellularized native kidney using clinically relevant, expandable patient-specific renal progenitors and endothelial cells may be a viable approach for the generation of a functional whole kidney. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Trigeminal perineural spread of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

  7. Renal involvement of mantle cell lymphona leading to end stage renal disease.

    Science.gov (United States)

    Lee, Hyeon Jeong; Seo, Jong Woo; Cho, Hyun Seop; Kang, Yeojin; Bae, Eun Jin; Lee, Dong Won; Jeon, Dae-Hong; Lee, Jong Sil; Chang, Se-Ho; Park, Dong Jun

    2012-01-01

    Mantle cell lymphoma (MCL), owing to its insensitivity to chemotherapy, has a poor prognosis, with a median survival of 3 years to 4 years. MCL frequently infiltrates other organs. However, reports involving kidney in living patients are rare. Here, we report a case of MCL with renal involvement leading to end stage renal disease that required renal replacement therapy. A 69-year-old man diagnosed with MCL 3 years earlier was admitted to our emergency room due to uremic symptoms. After eight cycles of chemotherapy, he had displayed complete remission, but experienced a recurrence 1.5 years later; after refusing chemotherapy, the patient was lost on follow-up in the final 10 months. On presentation at the emergency room, the patient's serum blood urea nitrogen was 109.5 mg/dL, and creatinine was 11.1 mg/dL. All serological markers for secondary glomerulonephritis were negative. Renal biopsy revealed 50% sclerosis of the glomerulus and small dense lymphocyte infiltration of the tubulo-interstitium. Similar cells were found on the gastric mucosa. Despite our recommendation for chemotherapy, he refused all treatments except for hemodialysis, which was maintained for 12 months until his death. This patient represents the first case report of the renal involvement of MCL leading to end stage renal disease.

  8. CD4 + T cells promote renal cell carcinoma proliferation via modulating YBX1.

    Science.gov (United States)

    Wang, Yong; Wang, Yiting; Xu, Liang; Lu, Xianqi; Fu, Donghe; Su, Jing; Geng, Hua; Qin, Guoxuan; Chen, Ruibing; Quan, Changyi; Niu, Yuanjie; Yue, Dan

    2018-02-01

    Renal cell carcinoma (RCC) is a common urologic tumor and the third leading cause of death among urological tumors. Recent studies demonstrate that RCC tumors are more heavily infiltrated by lymphocytes than other cancers. However, the exact roles played by CD4 + T cells in RCC proliferation remain unknown. In this study, we cocultured RCC cells with CD4 + T cells. Stable knockdown of YBX1 in RCC cells was constructed. The effects of CD4 + T cells, TGFβ1 and YBX1 on RCC cells were investigated using cell viability assays. In situ RCC nude mouse model was used to observe the tumor growth. The potential mechanisms of CD4 + T cells and YBX1 in RCC cells proliferation were explored by qRT-PCR and western blot. Expression of CD4, Foxp3 and TGFβ1 in RCC were quantified by immunohistochemical staining. The results indicated that CD4, Foxp3 and TGFβ1 were significantly up-regulated in RCC tissues. Human clinical sample and in vitro cell lines studies showed that RCC cells had better capacity than its surrounding normal kidney epithelial cells to recruit the CD4 + T cells. In vivo mouse model studies were consistent with the results by in vitro cell lines studies showing infiltrating T cells enhanced RCC cell proliferation. qRT-PCR and western blot exhibited that CD4 + T cells could enhance RCC cell proliferation via activating YBX1/HIF2α signaling pathway. Furthermore, CD4 + T cells functioned through inducing TGFβ1 expression. In a word, infiltrating CD4 + T cells promoted TGFβ1 expression in both RCC and T cells and regulated RCC cells proliferation via modulating TGFβ1/YBX1/ HIF2α signals. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Axitinib in sequential therapy in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Agata Kuchar

    2015-05-01

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

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

    Science.gov (United States)

    Sittig, Simone P; Køllgaard, Tania; Grønbæk, Kirsten; Idorn, Manja; Hennenlotter, Jörg; Stenzl, Arnulf; Gouttefangeas, Cécile; Thor Straten, Per

    2013-09-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were in the range of 1-17 (median = 5), and in several patients, the number of clonotypes expanded within tumor lesions resembled that observed among autologous peripheral blood mononuclear cells. Moreover, several of these clonotypes were identical in TILs and PBMCs. Flow cytometry data demonstrated that the general differentiation status of CD8 + TILs differed from that of circulating CD8 + T cells. Furthermore, PD-1 and LAG-3 were expressed by a significantly higher percentage of CD8 + RCC-infiltrating lymphocytes as compared with PBMCs obtained from RCC patients or healthy individuals. Thus, CD8 + TILs display a differentiated phenotype and express activation markers as well as surface molecules associated with the inhibition of T-cell functions. However, TILs are characterized by a low amount of expanded T-cell clonotypes.

  11. Renal Cell Carcinoma Mimicking Adrenal Tumor

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Moslemi

    2010-01-01

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

  12. Autologous dendritic cells combined with cytokine-induced killer cells in the treatment of metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Jin-chao ZHANG

    2016-10-01

    Full Text Available Objective  To evaluate the clinical efficacy, the immune function and follow-up observation of autologous dendritic cells (DCs combined with cytokine-induced killer (CIK cells in the treatment of metastatic renal cell carcinoma. Methods  Peripheral blood mononuclear cells (PBMCs were collected from 27 patients with metastatic renal cell carcinoma, and cultured in vitro to produce DCs and CIK cells. After sterility test, phenotypic characterization by flow cytometry and cell count, the produced DCs and CIK cells were then returned to the patient. DCs were given subcutaneously on day 7, 9, 11 and 13 respectively, after PBMCs collection, and CIK cells were given intravenously on day 11 and 13 respectively. This treatment regimen was repeated at a 3 months interval until the disease progresses. Clinical outcomes and immune function were recorded during the treatment period. Results  After DCs-CIK cells treatment, clinical efficacy showed an objective response rate (ORR of 37%, a disease control rate (DCR of 85% and 2 years overall survival rate of 81.5%. There were no significant changes of T cell subsets including CD3 +CD4+CD8–, CD3+CD4–CD8+, CD3+CD19–, CD3–CD19+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD3+HLA-DR–, CD3+HLA-DR+, CD3+CD28+CD8+ and Th2 cells except CD3+CD4+CD25+ T cells (Treg cells and Th1 in peripheral blood between pre-and post-treatment. No serious adverse events were observed. Conclusion  DCs-CIK cells immunotherapy provides a safe and effective treatment approach for patients with metastatic renal cell carcinoma, and may improve the immunosuppression status and enhance the anti-tumor immunity without obvious adverse reaction. DOI: 10.11855/j.issn.0577-7402.2016.10.07

  13. Pathological Bases and Clinical Impact of Intratumor Heterogeneity in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    López, José I; Angulo, Javier C

    2018-01-27

    Intratumor heterogeneity is an inherent event in tumor development that is receiving much attention in the last years since it is responsible for most failures of current targeted therapies. The purpose of this review is to offer clinicians an updated insight of the multiple manifestations of a complex event that impacts significantly patient's life. Clear cell renal cell carcinoma is the most common renal tumor and a paradigmatic example of a heterogeneous neoplasm. Next-generation sequencing has demonstrated that intratumor heterogeneity encompasses genetic, epigenetic, and microenvironmental variability. Currently accepted protocols of tumor sampling seem insufficient in unveiling intratumor heterogeneity with reliability and need to be updated. This variability challenges the precise morphological diagnosis, its molecular characterization, and the selection of optimal personalized therapies in clear cell renal cell carcinoma, a neoplasm traditionally considered chemo- and radio-resistant. We review the state of the art of the different approaches to intratumor heterogeneity in clear cell renal cell carcinomas, from the simple morphology to the most sophisticated massive sequencing tools.

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

    DEFF Research Database (Denmark)

    Brøchner, Anne C; Dagnaes-Hansen, Frederik; Toft, Palle

    2010-01-01

    , the mortality rate still remains above 50%. The causes of death are primarily extra-renal and include infection, shock, septicemia, and respiratory failure. We wanted to evaluate the cell-mediated inflammatory response of renal ischemia-reperfusion (I/R) and non-renal I/R, in blood and in distant organs. In our...

  15. 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.

  16. Metastatic Clear Cell Renal Cell Carcinoma Presenting with a Gingival Metastasis.

    Science.gov (United States)

    Ali, Rusha A E; Mohamed, Kamal E H

    2016-04-26

    Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation in a clinical trial, should be discussed with the patient despite the poor overall prognosis.

  17. Metastatic clear cell renal cell carcinoma presenting with a gingival metastasis

    Directory of Open Access Journals (Sweden)

    Rusha A.E. Ali

    2016-06-01

    Full Text Available Metastatic deposits to the oral cavity are exceptionally rare. The commonest tumor types metastasizing to the oral cavity include lung and breast carcinoma. Renal cell carcinoma is believed to be the third most common infra clavicular tumor to metastasize to the head and neck. We report a case where an oral cavity deposit was the initial presentation for an occult clear cell renal carcinoma. Additional therapeutic options, including immunotherapy, tyrosine kinase inhibitors, and participation in a clinical trial, should be discussed with the patient despite the poor overall prognosis.

  18. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Fengju Chen

    2016-03-01

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

  19. 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.)

  20. Recurrent renal cell cancer: 10 years or more after nephrectomy

    OpenAIRE

    Abara, Emmanuel; Chivulescu, Iolanda; Clerk, Nilam; Cano, Pablo; Goth, Alexis

    2010-01-01

    Localized renal cell carcinoma (RCC) responds well to surgery. Patients often question how long they have to be on surveillance after their surgery. Several follow-up patterns have been described in the literature. Until 2009, no published established Canadian guidelines existed to assist Canadian health-care practitioners in the surveillance of these patients. We present 3 cases of RCC that recurred 10 years or longer after the initial nephrectomy. These cases emphasize the need for careful ...

  1. Renal cell carcinoma with erythrocytosis and elevated erythropoietic stimulatory activity.

    Science.gov (United States)

    Burk, J R; Lertora, J J; Martinez, I R; Fisher, J W

    1977-08-01

    A case study is presented of a 55-year-old man who had clear cell renal carcinoma with pulmonary metastases and erythrocytosis. The increase in red blood cell mass was associated with an elevation in erythropoietic stimulatory activity in serum, pleural fluid, and tumor-cyst fluid as determined by the exhypoxic polycythemic mouse assay. It is postulated that the increased erythropoietic stimulatory activity represents autonomous tumor secretion of erythropoietin or an erythropoietin-like material. Electron microscopic studies confirmed the proximal tubular origin of this tumor.

  2. 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)

  3. 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)

  4. [Chromophobe renal cell carcinoma, an exceptional entity in childhood: a case report].

    Science.gov (United States)

    Fernández Pineda, I; Cabello Laureano, R; Maraví Petri, A; Carranza Carranza, A; Congregado Córdoba, J; De Agustín Asensio, J C

    2008-06-01

    Chromophobe renal cell carcinoma (CRCC) is a rare variant of renal carcinomas arising from the intercalated cells of the distal renal tubule and representing 5% among all renal tumors. Its biological behaviour is variable, less aggresive than clear cell renal carcinoma. Histochemical, ultrastructural and molecular genetic characteristics are different from other renal carcinomas. Age at presentation is about the 6th decade of life. We report an exceptional 10 year-old boy case with a CRCC. Diagnostic and therapeutic aspects for the management of this tumor are reviewed.

  5. 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

  6. Ultrastructural morphometry of nucleoli: potential usefulness for objective grading of clear cell renal cell carcinoma.

    Science.gov (United States)

    Lloreta-Trull, J; Bielsa-Galí, O; Domínguez-Solà, D; Arumí-Uría, M; Pavesi, M; Gelabert, A; Serrano-Figueras, S

    2001-01-01

    The authors attempted to determine the potential prognostic value of several ultrastructural morphometric parameters, including nuclear, nucleolar, and cytoplasmic features, that could be used in the objective and reproducible histological grading of clear cell renal cell carcinoma. Several nuclear and cytoplasmic parameters were assessed by ultrastructural morphometry in 26 consecutive cases of clear cell renal cell carcinoma. The nuclear and nucleolar sizes, the number of nucleoli per nuclear section and the number of marginated nucleoli, Fuhrman's nuclear grade, and Robson's stage were recorded. In addition, the proportion of cytoplasmic components was semiquantitatively estimated and compared to light microscopic appearance. Follow-up ranged from 5 to 15 years (mean = 10 years). Statistical evaluations were performed by means of the Pearson or Spearman correlation coefficient tests, and differences in survival were estimated, using the Mantel-Cox proportional risk method. Differences in survival among patients with a mean nuclear area over and under 160 microm2, and among those with a mean nucleolar area over and under 10 microm2, were statistically significant. (Cutoff points were selected at the median value for both parameters; Mantel-Cox test: chi2 = 7.102, p morphometric features, nucleolar area is the most useful in the reproducible and accurate grading of clear cell renal cell carcinoma.

  7. 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.

  8. Coexistence of Ovarian Cancer and Renal Cell Carcinoma

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    Kuo-How Huang

    2007-01-01

    Full Text Available Coexistence of ovarian cancer and renal cell carcinoma (RCC is extremely rare. Only one case was diagnosed in a total of 584 patients with RCC from 1982 to 2002 at our hospital. A 58-year-old woman presented with an enlarged girdle length for 3 months. Computed tomography scan showed a right cystic adnexal mass measuring 10 × 10 cm, and another tumor measuring 3 × 2 cm at the right kidney. She underwent debulking surgery and radical nephrectomy. Pathologic examination revealed right ovarian clear-cell carcinoma with peritoneal, omental, and fallopian tube metastasis, and conventional clear-cell renal carcinoma. RCC was strongly positive in epithelial membrane antigen (EMA staining and negative in estrogen receptors (ER, progesterone receptors (PR, 34bE12 (high molecular weight cytokeratin, and vimentin staining. Ovarian clear-cell carcinoma showed weakly positive results in EMA staining and negative results in ER, PR, 34bE12, and vimentin staining. Although chemotherapy was given, the patient died of disseminated ovarian cancer metastasis 20 months after operation. In conclusion, coexistence of RCC and ovarian cancer is rare and the pathogenesis remains to be clarified. [J Formos Med Assoc 2007;106(3 Suppl:S15-S19

  9. Novel treatment strategies in clear-cell metastatic renal cell carcinoma.

    NARCIS (Netherlands)

    Spronsen, D.J. van; Weijer, K.J.M. de; Mulders, P.F.A.; Mulder, P.H.M. de

    2005-01-01

    Metastatic renal-cell carcinoma (mRCC) is highly resistant to cytotoxic agents or hormones and is currently mainly treated with cytokine-based therapy. Transient responses and moderate survival advantages have been achieved in a subset of patients with these aspecific biological response modifiers.

  10. 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

  11. Recent developments in small molecule therapies for renal cell carcinoma.

    Science.gov (United States)

    Song, Minsoo

    2017-12-15

    Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and is known to be the 10th most common type of cancer in the world. Most of the currently available RCC drugs are tyrosine kinase inhibitors (TKIs). However, combination therapies of TKIs and immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors are the focus of most of the final stage clinical trials. Meanwhile, other small molecule therapies for RCC that target indoleamine-2,3-dioxygenase (IDO1), glutaminase, C-X-C chemokine receptor 4 (CXCR4), and transglutaminase 2 (TG2) are emerging as the next generation of therapeutics. In this review, these three major streams for the development of small molecule drugs for RCC are described. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

    OpenAIRE

    Shujue Li; Wenqi Wu; Wenzheng Wu; Xiaolu Duan; Zhenzhen Kong; Guohua Zeng

    2016-01-01

    Background/Aims: The interactions between calcium oxalate monohydrate (COM) crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. Methods: Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-48...

  13. 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

  14. Role of surgery in advanced/metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Suresh Bhat

    2010-01-01

    Full Text Available Metastatic renal cell cancer (RCC is a malignant disease without curative treatment. These patients are usually symptomatic and desperate for effective palliative treatment. Radiotherapy, chemotherapy, and hormonal therapy are not effective in these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (which includes cytokines or targeted molecules, and metastasectomy have been shown to be useful in prolonging the survival and improving the quality of life in a select group of patients with metastatic renal cancer. Patients with oligometastatic disease, good performance status, and delayed presentation of the secondaries have better results following this integrated approach. Although there is some controversy regarding the order in which nephrectomy and systemic therapy are to be instituted, well-controlled studies like the South West Oncology Group and European organization research and treatment of cancer have shown that upfront nephrectomy gives better survival compared to neoadjuvant systemic therapy followed by nephrectomy. This order is the standard presently. Of late, with better understanding of the genetic basis and the biology of the various subtypes of renal cell carcinoma, targeted molecular therapies have emerged as an equally effective alternative therapy to cytokines. Recent reports have proven that targeted therapy is more effective with comparable side effects. Metastasectomy in a subgroup of patients improves survival and quality of life specifically in those with lung secondaries and painful bone metastases.

  15. 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.

  16. Thyroid Metastases from Renal Cell Carcinoma: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Alessandro Sindoni

    2010-01-01

    Full Text Available The thyroid gland is a rare site of clinically detectable tumor metastasis and kidneys are frequently the site of the parent malignancy. In the present review on thyroid metastases from renal cell carcinoma, cases were searched on PubMed by entering the strings: “renal carcinoma [or“hypernephroma”] AND thyroid metastasis/metastases”. Thus, we retrieved a total of 111 cases that were published between 1964 and 2007, a total that became 113 by adding two patients observed by us. The female to male ratio was 1.35:1. The primary renal cancer was almost always unilateral (90% (with no significant side preference and only rarely bilateral (9% in men, 4% in women, whereas bilaterality of thyroid metastases was relatively more frequent (28%. Thyroid metastasis from renal cancer was commonly single with a unique node that appears solid and hypoechoic at ultrasonography, approximately 9 years after nephrectomy. Concordance of lateralization was insignificantly greater for the right kidney/right thyroid lobe pattern (54% than for the left kidney/left thyroid lobe pattern (40%, regardless of gender. Finally, survival was longer for women. Thyroid metastases, even if rare in the clinical practice, must be considered in the differential diagnosis of a thyroid nodule, particularly in patients who have a history of malignancies.

  17. Thyroid metastases from renal cell carcinoma: review of the literature.

    Science.gov (United States)

    Sindoni, Alessandro; Rizzo, Massimo; Tuccari, Giovanni; Ieni, Antonio; Barresi, Valeria; Calbo, Letterio; Cucinotta, Eugenio; Trimarchi, Francesco; Benvenga, Salvatore

    2010-04-01

    The thyroid gland is a rare site of clinically detectable tumor metastasis and kidneys are frequently the site of the parent malignancy. In the present review on thyroid metastases from renal cell carcinoma, cases were searched on PubMed by entering the strings: "renal carcinoma [or "hypernephroma"] AND thyroid metastasis/metastases". Thus, we retrieved a total of 111 cases that were published between 1964 and 2007, a total that became 113 by adding two patients observed by us. The female to male ratio was 1.35:1. The primary renal cancer was almost always unilateral (90%) (with no significant side preference) and only rarely bilateral (9% in men, 4% in women), whereas bilaterality of thyroid metastases was relatively more frequent (28%). Thyroid metastasis from renal cancer was commonly single with a unique node that appears solid and hypoechoic at ultrasonography, approximately 9 years after nephrectomy. Concordance of lateralization was insignificantly greater for the right kidney/right thyroid lobe pattern (54%) than for the left kidney/left thyroid lobe pattern (40%), regardless of gender. Finally, survival was longer for women. Thyroid metastases, even if rare in the clinical practice, must be considered in the differential diagnosis of a thyroid nodule, particularly in patients who have a history of malignancies.

  18. Generation of induced pluripotent stem cells from renal tubular cells of a patient with Alport syndrome

    Directory of Open Access Journals (Sweden)

    Chen WB

    2015-08-01

    Full Text Available Wenbiao Chen,1,* Jianrong Huang,2,* Xiangqi Yu,1 Xiaocong Lin,1 Yong Dai11The Clinical Medical Research Center, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, 2Department of Hemodialysis, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong, 3Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, People's Republic of China *These authors contributed equally to this workAbstract: Alport syndrome (AS is a hereditary disease that leads to kidney failure and is caused by mutations in the COL4A3, COL4A4, and COL4A5 genes that lead to the absence of collagen α3α4α5 (IV networks in the mature kidney glomerular basement membrane. Approximately 80% of AS is X-linked because of mutations in COL4A5, the gene encoding the alpha 5 chain of type IV collagen. To investigate the pathogenesis of AS at the genetic level, we generated induced pluripotent stem cells (iPSCs from renal tubular cells of a patient with AS. The successful iPSC generation laid the foundation to master the repair of the COL4A5 gene and to evaluate the differentiation of iPSC into Sertoli cells and the accompanying epigenetic changes at each stage. The generation of iPSCs from AS patients not only confirms that iPSCs could be generated from renal tubular cells, but also provides a novel type of genetic therapy for AS patients. In this study, we generated iPSCs from renal tubular cells via ectopic expression of four transcription factors (Oct4, Sox2, c-myc, and Klf4. According to the human embryonic stem cell (hESC charter, iPSC formation was confirmed by comparatively analyzing hESC markers via colony morphology, immunohistochemistry, qRT-PCR, flow cytometry, gene expression profiling of the three germ layers, and karyotyping. Our results demonstrated that iPSCs were similar to hESCs with regard to morphology, proliferation, hESC-specific surface marker expression, and differentiation into the cell types of the

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

    Science.gov (United States)

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

    2017-04-01

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

  20. 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

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

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    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.

  2. 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

  3. Analysis of renal cancer cell lines from two major resources enables genomics-guided cell line selection

    Science.gov (United States)

    Sinha, Rileen; Winer, Andrew G.; Chevinsky, Michael; Jakubowski, Christopher; Chen, Ying-Bei; Dong, Yiyu; Tickoo, Satish K.; Reuter, Victor E.; Russo, Paul; Coleman, Jonathan A.; Sander, Chris; Hsieh, James J.; Hakimi, A. Ari

    2017-05-01

    The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines.

  4. The value of molecular genetic analysis in the diagnosis and prognosis of renal cell tumours.

    Science.gov (United States)

    Kovacs, G

    1994-01-01

    Renal cell tumours have a heterogeneous morphology, which may also be changed during tumour progression. Through the use of molecular cytogenetic techniques, it has become possible to divide renal cell tumours into genetically well-defined entities. Papillary renal cell tumours are characterized by loss of the Y chromosome and trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20. Non-papillary renal cell carcinomas show a specific loss of chromosome 3p and trisomy of chromosome 5q sequences and frequent loss of chromosome 6q, 8p, 9 and 14q sequences. Chromophobe renal cell carcinomas are marked by a highly specific combination of loss of chromosomes 1, 2, 6, 10, 13, 17 and 21 and gross rearrangement of mitochondrial DNA. Subsets of renal oncocytomas show minimal karyotype alterations or translocation 11q13;? or loss of the Y chromosome and chromosome 1. There are some data suggesting that molecular genetic markers may be used not only for diagnosing of renal cell tumours but also for predicting the prognosis of tumour subtypes. Trisomy of chromosomes 7 and 17 and loss of the Y chromosome marks papillary renal cell adenomas, whereas additional trisomies such as those of chromosomes 3q, 8, 12, 16 and 20 are associated with papillary renal cell carcinomas. Although non-papillary renal cell tumours develop as a carcinoma, their clinical behaviour is in strong correlation with secondary karyotype changes such as loss of chromosomes 6q, 8p, 9 and 14q.

  5. [Late thyroid and pancreas metastases from a clear cell renal carcinoma. Report of two cases].

    Science.gov (United States)

    Urdiales-Viedma, Mariano; Luque, Rafael J; Elósegui-Martínez, Fernando; Martos-Padilla, Sebastián; López-Urdiales, Rafael

    2008-01-01

    To report two cases of late metastases of clear cell renal cell carcinoma. Two patients, a male and a female with history of nephrectomy 17 and 16 years before for renal cell carcinomas, presented new tumours in the thyroid and pancreas, which were excised. Pathology reported that both lesions were clear cell tumours and immunohistochemically they were consistent with metastases from clear renal cell carcinomas. 1) Previous history of any type of carcinoma should suggest the possibility of metastases when facing a thyroid or pancreatic nodule. 2) All-life follow-up should be made, nephrectomy (resection) for a renal cell carcinoma. 3) In the presence of a clear cell tumour of the thyroid or pan-creatic glands, the differential diagnosis must always include metastatic renal cell carcinoma. 4) The treatment of choice is surgical resection.

  6. 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.

  7. A familial case of renal cell carcinoma and a t(2;3) chromosome translocation

    NARCIS (Netherlands)

    Koolen, MI; van der Meyden, PM; Bodmer, D; Eleveld, M; van der Looij, E; Brunner, H; Smits, A; Smeets, D; van Kessel, AG

    Cytogenetic analysis was performed on peripheral blood lymphocytes of members of a family with inherited renal cell cancer. Four family members in three generations developed multiple/bilateral renal cell carcinomas of the clear cell type. In one additional case a bladder carcinoma was diagnosed. In

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

    Directory of Open Access Journals (Sweden)

    K J Kelly

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

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

    Science.gov (United States)

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

    2015-01-01

    Metastatic tumors account for 1.4-2.5% of thyroid malignancies. About 25-30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles "suggestive" of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of "de novo" thyroid nodules in oncologic patients must be always considered and studied. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

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

    2013-12-15

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

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

    International Nuclear Information System (INIS)

    Ak, I.; Can, C.

    2005-01-01

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

  12. 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.

  13. Reevaluation of renal cell carcinoma and perirenal fat invasion only.

    Science.gov (United States)

    Jeon, Hwang Gyun; Jeong, In Gab; Kwak, Cheol; Kim, Hyeon Hoe; Lee, Sang Eun; Lee, Eunsik

    2009-11-01

    Controversy continues over whether perirenal fat invasion in pT3a renal cell carcinoma is a prognostic factor. We investigated the prognosis of renal cell carcinoma with perirenal fat invasion compared to the prognosis of other pathological stages by tumor size. We reviewed the medical records of 946 patients who underwent curative surgery for pT1-pT3bN0M0 renal cell carcinoma between 1988 and 2006. Patients with pT3a stage disease and perirenal fat invasion only were divided into 2 subgroups by a 7 cm tumor size cutoff. The prognostic impact of perirenal fat invasion on disease-free and cancer specific survival was investigated. Patients with perirenal fat invasion and lesions greater than 7 cm had lower 5-year disease-free (49.5% vs 77.2%, p = 0.004) and cancer specific (58.5% vs 95.6%, p = 0.003) survival than those with lesions 7 cm or less. Patients with perirenal fat invasion and lesions 7 cm or less had similar 5-year disease-free and cancer specific survival compared to those with pT1 tumors (p = 0.109 and 0.602, respectively). For tumors 7 cm or less multivariate analysis showed that perirenal fat invasion was not a significant predictor of disease-free (p = 0.119) or cancer specific (p = 0.208) survival. In contrast, perirenal fat invasion was an independent prognostic factor for disease-free (p = 0.002) and cancer specific (p = 0.027) survival in patients with tumors greater than 7 cm. Findings suggest that the prognostic significance of perirenal fat invasion depends on primary tumor size. Perirenal fat invasion included in the pT3a stage regardless of tumor size should be reevaluated by tumor size for a more accurate patient prognosis.

  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. 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.

  16. Distinct Cytoplasmic Expression of KL-6 Mucin in Chromophobe Renal Cell Carcinoma: A Comparative Immunohistochemical Study with Other Renal Epithelial Cell Tumors

    International Nuclear Information System (INIS)

    Fukushima, Mana; Higuchi, Kayoko; Shimojo, Hisashi; Uehara, Takeshi; Ota, Hiroyoshi

    2012-01-01

    The presence of cytoplasmic sialyl glycoproteins is a conspicuous feature in chromophobe renal cell carcinoma (RCC). We compared the immunohistochemical expression of sialyl glycoproteins in chromophobe RCC with that in other types of renal tumors. Formalin-fixed, paraffin-embedded tissues of surgically resected renal tumors (chromophobe RCC, 14 cases [10 cases of classic type and 4 cases of eosinophilic variant]; oncocytoma, 7 cases; and clear cell RCC, 9 cases) and kidneys from immature infants (4 cases) were immunostained with antibodies against sialyl glycoproteins (anti-KL-6 and anti-sialyl MUC1 antibodies). Cytoplasmic expression of KL-6 and sialyl MUC1 was distinctive in the chromophobe RCC and renal oncocytoma cells, and in the intercalated cells in collecting duct epithelia. Apical-surface staining of these sialyl glycoproteins was predominantly observed in clear RCC, in the epithelia of the distal tubule and collecting duct, and in the neonatal renal proximal tubule, but not in those of the adult renal proximal tubule. The above-mentioned observations provide additional evidence for similar phenotypic profiles of chromophobe RCC and renal oncocytoma, and the intercalated cells in collecting ducts and the oncofetal expression of sialyl glycoproteins in clear cell RCC. KL-6 is a potential tumor marker for renal tumors

  17. CD163-positive cancer cells are potentially associated with high malignant potential in clear cell renal cell carcinoma.

    Science.gov (United States)

    Ma, Chaoya; Horlad, Hasita; Ohnishi, Koji; Nakagawa, Takenobu; Yamada, Sohsuke; Kitada, Shohei; Motoshima, Takanobu; Kamba, Tomomi; Nakayama, Toshiyuki; Fujimoto, Naohiro; Takeya, Motohiro; Komohara, Yoshihiro

    2018-03-01

    CD163 is preferentially expressed by monocyte/macrophages; however, recent studies using immunohistochemistry (IHC) have reported that some cancer cells also express CD163. In the present IHC study, we investigated CD163 staining of cancer cells and macrophages in clear cell renal cell carcinoma (ccRCC) tissues and determined the relationship between cancer cell CD163 expression and clinical prognosis in patients with ccRCC. IHC for CD163 was performed in ccRCC tissues from 103 patients. CD163-positive cancer cells were detected in 35% of the patients (36/103); however, the positive signals on cancer cells were significantly lower than those on macrophages. CD163-positive cancer cells were preferentially detected in patients with high T classification, and females, and were significantly associated with shortened progression-free survival and a lower overall survival ratio. Notably, a high intensity of CD163-positive macrophage infiltration was detected in the CD163-positive cancer cell-high tumor areas. Although CD163 mRNA was detected in cultured macrophages, no CD163 mRNA was detected in two cultured RCC cell lines. The detailed mechanism by which a positive signal is detected on cancer cells has not been clarified. Detection of the CD163 antigen on cancer cells might be a useful marker for evaluating the clinical course of patients with ccRCC.

  18. Recurrent renal cell cancer: 10 years or more after nephrectomy.

    Science.gov (United States)

    Abara, Emmanuel; Chivulescu, Iolanda; Clerk, Nilam; Cano, Pablo; Goth, Alexis

    2010-04-01

    Localized renal cell carcinoma (RCC) responds well to surgery. Patients often question how long they have to be on surveillance after their surgery. Several follow-up patterns have been described in the literature. Until 2009, no published established Canadian guidelines existed to assist Canadian health-care practitioners in the surveillance of these patients. We present 3 cases of RCC that recurred 10 years or longer after the initial nephrectomy. These cases emphasize the need for careful long-term follow-up, as recommended in the Canadian Urological Association guidelines. We also discuss the optimism of prolonged disease survival in the era of novel therapeutic agents that target angiogenesis.

  19. Targeting HIF2α Translation with Tempol in VHL-Deficient Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    Ghosh, Manik C.; Ghosh, Sanchari; Yang, Youfeng; Gupta, Gopal; DeGraff, William; Krishna, Murali C.; Mitchell, James B.; Rouault, Tracey A.; Linehan, W. Marston

    2012-01-01

    The tumor suppressor gene, Von Hippel-Lindau (VHL), is frequently mutated in the most common form of kidney cancer, clear cell renal cell carcinoma (CCRCC). In hypoxic conditions, or when there is a VHL mutation, the hypoxia inducible factors, HIF1α and HIF2α, are stabilized and transcribe a panel of genes associated with cancer such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). Recent studies in clear cell kidney cancer have suggested that HIF2α, but not HIF1α, is the critical oncoprotein in the VHL pathway. Therefore, targeting HIF2α could provide a potential therapeutic approach for patients with advanced CCRCC. Since iron regulatory protein 1 (IRP1) is known to inhibit the translation of HIF2α, we investigated whether Tempol, a stable nitroxide that activates IRP1 towards IRE-binding, might have a therapeutic effect on a panel of human CCRCC cells expressing both HIF1α and HIF2α. We first evaluated the protein expression of HIF1α and HIF2α in 15 different clear cell renal carcinoma cell lines established from patient tumors in our laboratory. Tempol decreased the expression of HIF2α, and its downstream targets in all the cell lines of the panel. This effect was attributed to a dramatic increase of IRE-binding activity of IRP1. Several cell lines were found to have an increased IRP1 basal activity at 20% O2 compared to 5% O2, which may lower HIF2α expression in some of the cell lines in a VHL-independent manner. Taken together our data identify Tempol as an agent with potential therapeutic activity targeting expression of HIF2α in VHL-deficient clear cell kidney cancer and illustrate the importance of studying biochemical processes at relevant physiological O2 levels. PMID:23178531

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2013-11-01

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

  2. 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.

  3. Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.

    Science.gov (United States)

    Morizane, Ryuji; Monkawa, Toshiaki; Fujii, Shizuka; Yamaguchi, Shintaro; Homma, Koichiro; Matsuzaki, Yumi; Okano, Hideyuki; Itoh, Hiroshi

    2014-01-01

    Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP)-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.

  4. Increased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Nordsmark, Marianne

    2009-01-01

    PURPOSE: The administration of interleukin-2 (IL-2) may increase the frequency of peripherally circulating FOXP3-positive regulatory immune cells, thus potentially compromising this treatment option for patients with metastatic renal cell carcinoma. The impact of IL-2-based therapy...... on the accumulation of FOXP3-positive immune cells in the tumor microenvironment in metastatic renal cell carcinoma is unknown. EXPERIMENTAL DESIGN: Baseline (n = 58) and on-treatment (n = 42) tumor core biopsies were prospectively obtained from patients with clear cell metastatic renal cell carcinoma before...... and during IL-2-based immunotherapy. Immunohistochemical expression of FOXP3 was estimated by stereological counting technique and correlated with other immune cell subsets and overall survival. RESULTS: A significant increase in absolute intratumoral FOXP3-positive immune cells was observed comparing...

  5. 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

  6. Current and Emerging Therapeutic Targets for Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Zarrabi, Kevin; Wu, Shenhong

    2018-04-02

    The treatment of advanced renal cell carcinoma has evolved dramatically over recent years. In this review, we will summarize current and emerging therapies based on molecular targets and provide insight into treatment strategy for metastatic renal cell carcinoma. We have witnessed a paradigm shift in the therapeutic landscape as treatment was formerly reliant on cytokine-based agents which have now been replaced with therapies targeting angiogenesis, mammalian target of rapamycin pathways, and immune responses. These dramatic changes are primarily due to our improved understanding of the underlying mutations and molecular mechanisms leading to tumorigenesis and progression. We now have targeted agents in the form of small-molecule tyrosine kinase inhibitors, monoclonal antibodies, and mTOR inhibitors. Moreover, immunotherapy-targeting checkpoints of T-lymphocyte activity has provided increased overall survival and a new class of agents with potential to radically change the treatment options. With these agents and their combination, durable responses are increasingly seen even though treatment resistance remains a huge challenge. New treatment strategies are rapidly developing and the therapeutic landscape is expected for further evolution.

  7. Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall'Oglio

    2005-02-01

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

  8. Factors impacting survival in children with renal cell carcinoma.

    Science.gov (United States)

    Rialon, Kristy L; Gulack, Brian C; Englum, Brian R; Routh, Jonathan C; Rice, Henry E

    2015-06-01

    Renal cell carcinoma (RCC) is an uncommon tumor in the pediatric population. We examined a large national cancer database to determine outcomes for children with RCC and to identify variables affecting long-term survival. The National Cancer Data Base (NCDB) was queried for patients age 0 to 17 years diagnosed with RCC from 1998-2011. Patient demographics, tumor stage and characteristics, management, and outcomes were evaluated. A total of 304 children met inclusion criteria. Overall, 39% of children had stage I disease, 16% stage II, 33% stage III, and 12% stage IV. One-year and five-year survival for all children was 87% and 70%, respectively. Eighty-six percent of patients underwent surgical resection. In comparison to children who underwent complete nephrectomy, patients undergoing partial nephrectomy had smaller tumors and were of lower clinical stages. Survival following partial resection was 100% at one and five years. Age and gender had no significant impact on survival. Survival was negatively impacted by increasing tumor size (PChildren with renal cell carcinoma who undergo surgical resection have excellent one-year and five-year survival. Overall survival is significantly affected by pathologic stage, tumor size, and nodal status. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The role of glutathione transferases in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ćorić Vesna

    2016-01-01

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

  10. Prognostic significance of metallothionein expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Moraitis Epaminondas

    2005-01-01

    Full Text Available Abstract Background Metallothionein (MT protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. Patients and methods The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival. Results Positive MT staining was present in 21 cases (49%, being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. Conclusions The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic

  11. 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

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Agnieszka Buraczewska

    2017-01-01

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

  14. E. adenophorum Induces Cell Cycle and Apoptosis of Renal Cells through Mitochondrial Pathway and Caspase Activation in Saanen Goat.

    Directory of Open Access Journals (Sweden)

    Yajun He

    Full Text Available The cytotoxicity effects of E. adenophorum on cell cycle and apoptosis of renal cells in Saanen goat was evaluated by TUNEL, DAPI, AO/EB staining, DNA fragmentation assay, Caspase activity, Western-blot, qRT-PCR and flow cytometry analysis. 16 saanen goats randomly divided into four groups were fed on 0%, 40%, 60% and 80% E. adenophorum diets. The Results showed that E. adenophorum induced typical apoptotic features of renal cells. E. adenophorum significantly suppressed renal cells viability, caused cell cycle activity arrest and induced typical apoptotic features in a dose-dependent manner. However, the protein levels of Fas/FasL, Bid and caspase-8 did not appear significant changes in the process of E. adenophorum-induced apoptosis. Moreover, E. adenophorum administration slightly decreased Bcl-2 expression, promoted Bax translocation to mitochondria, triggered the release of Cyt c from mitochondria into cytosol and activated caspase-9, -3, and cleaved PARP. The mitochondrial p53 translocation was significantly activated, accompanied by a significant increase in the loss of ΔΨm, Cyt c release and caspase-9 activation. Above all, these data suggest that E. adenophorum induces renal cells apoptosis via the activation of mitochondria-mediated apoptosis pathway in renal cells. These findings may provide new insights to understand the mechanisms involved in E. adenophorum-caused cytotoxicity of renal cells.

  15. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-15

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

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

    International Nuclear Information System (INIS)

    Kim, Jeong Jae; Kim, Bong Soo; Huh, Jung Sik; Park, Kyung Gi; Choi, Guk Myung; Kim, Seung Hyoung; Maeng, Young Hee

    2015-01-01

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

  18. Fusion of bone marrow-derived cells with renal tubules contributes to renal dysfunction in diabetic nephropathy.

    Science.gov (United States)

    Yamashita, Tomohisa; Fujimiya, Mineko; Nagaishi, Kanna; Ataka, Koji; Tanaka, Marenao; Yoshida, Hideaki; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki; Miura, Tetsuji

    2012-04-01

    Although diabetic nephropathy (DN) is a major cause of end-stage renal disease, the mechanism of dysfunction has not yet been clarified. We previously reported that in diabetes proinsulin-producing bone marrow-derived cells (BMDCs) fuse with hepatocytes and neurons. Fusion cells are polyploidy and produce tumor necrosis factor (TNF)-α, ultimately causing diabetic complications. In this study, we assessed whether the same mechanism is involved in DN. We performed bone marrow transplantation from male GFP-Tg mice to female C57BL/6J mice and produced diabetes by streptozotocin (STZ) or a high-fat diet. In diabetic kidneys, massive infiltration of BMDCs and tubulointerstitial injury were prominent. BMDCs and damaged tubular epithelial cells were positively stained with proinsulin and TNF-α. Cell fusion between BMDCs and renal tubules was confirmed by the presence of Y chromosome. Of tubular epithelial cells, 15.4% contain Y chromosomes in STZ-diabetic mice, 8.6% in HFD-diabetic mice, but only 1.5% in nondiabetic mice. Fusion cells primarily expressed TNF-α and caspase-3 in diabetic kidney. These in vivo findings were confirmed by in vitro coculture experiments between isolated renal tubular cells and BMDCs. It was concluded that cell fusion between BMDCs and renal tubular epithelial cells plays a crucial role in DN.

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

    Directory of Open Access Journals (Sweden)

    Isabella Dash

    2010-12-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  1. MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression.

    Science.gov (United States)

    Marona, Paulina; Górka, Judyta; Mazurek, Zofia; Wilk, Waclaw; Rys, Janusz; Majka, Marcin; Jura, Jolanta; Miekus, Katarzyna

    2017-09-15

    Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VE-cadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC. Cancer Res; 77(18); 4905-20. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. 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.

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

    Science.gov (United States)

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

    2012-09-01

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

  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. 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.

  6. Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal

    2014-01-01

    of published biomarkers to predict the survival of patients with clear cell kidney cancer in an independent patient cohort. Only one molecular test adds prognostic information to routine clinical assessments. This marker showed good and poor prognosis results within most individual cancers. Future biomarkers......BackgroundCandidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated. ObjectiveTo validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising...... markers to guide biomarker optimisation. Design, setting, and participantsCancer-specific survival (CSS) for each of 28 identified genetic or transcriptomic biomarkers was assessed in 350 ccRCC patients. ITH was interrogated in a multiregion biopsy data set of 10 ccRCCs. Outcome measurements...

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

    Directory of Open Access Journals (Sweden)

    Thomas C. Wehler

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  9. State-of-the-art surgical management of renal cell carcinoma.

    Science.gov (United States)

    Thiel, David D; Winfield, Howard N

    2007-09-01

    There is a recognizable increase in the incidence of renal cell carcinoma and a parallel rise in the surgical management of renal cell carcinoma has occurred. However, recent literature shows that not all small, suspected renal cell carcinoma needs to be treated surgically, especially in elderly patients or those with multiple medical comorbidities. The surgical options for renal cell carcinoma have expanded from traditional open nephrectomy to partial nephrectomy and, at present, more recent outcomes data are available for the laparoscopic versions of these surgeries. Short-term results of thermal ablative technology (radiofrequency and cryoablation) show real promise as minimally invasive therapies. This review examines the most up-to-date outcomes and future directions of the surgical management of renal cell carcinoma.

  10. 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.

  11. Isolation and characterization of progenitor-like cells from human renal proximal tubules.

    Science.gov (United States)

    Lindgren, David; Boström, Anna-Karin; Nilsson, Kristina; Hansson, Jennifer; Sjölund, Jonas; Möller, Christina; Jirström, Karin; Nilsson, Elise; Landberg, Göran; Axelson, Håkan; Johansson, Martin E

    2011-02-01

    The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. 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.

  13. 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

  14. 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.

  15. Perfluorooctanesulfonate Mediates Renal Tubular Cell Apoptosis through PPARgamma Inactivation.

    Directory of Open Access Journals (Sweden)

    Li-Li Wen

    Full Text Available Perfluorinated chemicals (PFCs are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs. In addition, PFOS increased transcription of inflammatory cytokines (i.e., TNFα, ICAM1, and MCP1 by NFκB activation. Conversely, PFOS reduced the mRNA levels of antioxidative enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase, as a result of reduced PPARγ transactivational activity by using reporter and chromatin immuoprecipitation (ChIP assays. PFOS reduced the protein interaction between PPARγ and PPARγ coactivator-1 alpha (PGC1α by PPARγ deacetylation through Sirt1 upregulation, of which the binding of PPARγ and PGC1α to a peroxisome proliferator response element (PPRE in the promoter regions of these antioxidative enzymes was alleviated in the ChIP assay. Furthermore, Sirt1 also deacetylated p53 and then increased the binding of p53 to Bax, resulting in increased cytosolic cytochrome C. The effect of PPARγ inactivation by PFOS was validated using the PPARγ antagonist GW9662, whereas the adverse effects of PFOS were prevented by PPARγ overexpression and activators, rosiglitozone and L-carnitine, in RTCs. The in vitro finding of protective effect of L-carnitine was substantiated in vivo using Balb/c mice model subjected to PFOS challenge. Altogether, we provide in vivo and in vitro evidence for the protective mechanism of L-carnitine in eliminating PFOS-mediated renal injury, at least partially, through PPARγ activation.

  16. Risk models for patients with localised renal cell carcinoma.

    Science.gov (United States)

    Velis, J M; Ancizu, F J; Hevia, M; Merino, I; García, A; Doménech, P; Algarra, R; Tienza, A; Pascual, J I; Robles, J E

    2017-11-01

    We conducted a retrospective analysis of our series to assess the factors that influenced disease-free survival (DFS) and cancer-specific survival (CSS) for patients with localised renal cell carcinoma (RCC). We also created our own risk groups. Between January 1990 and December 2012, 596 patients underwent surgery for localised RCC (clear cell, papillary or chromophobe). Using Cox regression models, we analysed the clinical-pathological variables that influenced DFS and CSS and designed risk groups for DFS and CSS with the variables. The median follow-up for the series was 5.96 years. By the end of the study, 112 patients (18.8%) had a recurrence of the disease, with DFS rates of 82%, 77% and 72% at 5, 10 and 15 years, respectively. The independent factors that influenced DFS in the multivariate study were the following: A Furhman grade of 3-4, haematuria, lymphocytic or vascular invasion, the presence of tumour necrosis and a disease stage pT3-pT4. Furthermore, by the end of the study, 57 patients (9.6%) died due to renal cancer, with CSS rates of 92%, 86% and 83% at 5, 10 and 15 years, respectively. The independent factors that influenced CSS in the multivariate study were the following: A Furhman grade of 3-4, perinephric fat invasion and the presence of tumour necrosis. Factors in addition to the disease stage pT3-pT4 in patients with localised RCC are important, such as the presence of haematuria and lymphocytic or vascular invasion for DFS. A Furhman grade of 3-4 and the presence of tumour necrosis are especially relevant for DFS and CSS. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    An Ren

    2015-01-01

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

  19. 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.

  20. Intra-renal slow cell-cycle cells contribute to the restoration of kidney tubules injured by ischemia/reperfusion.

    Science.gov (United States)

    Kim, Jinu; Kim, Jee In; Na, Yeon Kyung; Park, Kwon Moo

    2011-09-01

    Renal epithelial cells damaged by ischemia/reperfusion (I/R) can be restored by timely and appropriate treatment. Recent studies have reported that intra renal adult kidney stem cells contribute to the restoration of tubules damaged by I/R. Here, we determined the role of adult tubular cells in the restoration of damaged tubules. We labeled slow cell-cycle cells (SCCs) with 5-bromo-2'-deoxyuridine (BrdU) and investigated their location in the kidneys as well as their contribution to the restoration of tubular cells damaged by I/R injury in mice. Thirty minutes of bilateral ischemia resulted in severe disruption of tubular epithelial cells along with a decline in renal function. The post-ischemic disruption of tubular epithelial cells was most severe in the S3 segment of the outer stripe of the outer medulla. Damaged tubules demonstrated gradual recovery of renal function over time. BrdU-labeled SCCs were mainly observed in tubules located at the junction of cortex and outer medulla, as well as in the inner medulla. The tubular SCCs expressed functional tubule cell markers such as Na/K-ATPase, Na-K-Cl cotransporter-2, and aquaporin 1 and 2. BrdU-labeled SCCs survived I/R injury and proliferated. These results demonstrate that SCCs present in tubules contribute to the restoration of tubular epithelial cells injured by I/R.

  1. 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)

  2. [Contribution of stem cells to renal repair after ischemia/reperfusion].

    Science.gov (United States)

    Baud, Laurent; Haymann, Jean-Philippe; Bellocq, Agnès; Fouqueray, Bruno

    2005-04-01

    Repair of inflammatory and/or ischemic renal injury involves endothelial, mesangial and epithelial regeneration. These structures may be rebuilt by resident progenitor cells and bone marrow-derived stem cells. Resident progenitor cells in adult kidney have not yet been conclusively identified. They are likely to be slowly cycling cells located mainly in the outer medulla and renal papilla. In glomerulonephritis with mesangiolysis, mesangial regenera- tion involves progenitor cells migrating from the juxtaglomerular apparatus and also bone marrow-derived cells. In acute ischemic renal failure, epithelial regeneration of proximal tubules results from the migration, proliferation and differentiation of resident progenitor cells; bone marrow-derived cells may play an accessory role. Molecular mechanisms underlying these repair processes could be targets for new therapeutic approaches.

  3. 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

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current ICl swell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The ICl swell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates ICl swell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect ICl swell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on ICl

  4. [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.

  5. Radiotherapy for renal cell carcinoma: renaissance of an overlooked approach.

    Science.gov (United States)

    Siva, Shankar; Kothari, Gargi; Muacevic, Alexander; Louie, Alexander V; Slotman, Ben J; Teh, Bin S; Lo, Simon S

    2017-09-01

    Conventional radiotherapy previously had a limited role in the definitive treatment of renal cell carcinoma (RCC), owing to the disappointing outcomes of several trials and the perceived radioresistance of this type of cancer. In this context, radiotherapy has been relegated largely to the palliation of symptoms in patients with metastatic disease, with variable rates of response. Following the availability of newer technologies that enable safe delivery of high-dose radiotherapy, stereotactic ablative radiotherapy (SABR) has become increasingly used in patients with RCC. Preclinical evidence demonstrates that RCC cells are sensitive to ablative doses of radiotherapy (≥8-10 Gy). Trials in the setting of intracranial and extracranial oligometastases, as well as primary RCC, have demonstrated excellent tumour control using this approach. Additionally, an awareness of the capacity of high-dose radiation to stimulate antitumour immunity has resulted in novel combinations of SABR with immunotherapies. Here we describe the historical application of conventional radiotherapy, the current biological understanding of the effects of radiation, and the clinical evidence supporting the use of ablative radiotherapy in RCC. We also explore emerging opportunities to combine systemic targeted agents or immunotherapies with radiation. Radiotherapy, although once an overlooked approach, is moving towards the forefront of RCC treatment.

  6. 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.

  7. [A case of multilocular cystic renal cell carcinoma treated by partial nephrectomy associated with adrenal tumor].

    Science.gov (United States)

    Fukuoka, H; Ishibashi, Y; Fujinami, K; Tsuchiya, F; Sakanishi, S

    1994-12-01

    A case of multilocular cystic renal cell carcinoma was reported. The patient was 69-year-old male who had been examined for postoperative study of gastric cancer by abdominal CT. The abdominal CT incidentally revealed right adrenal tumor which was non-functional and multilocular cysts in the lower pole of the right kidney. Selective renal arteriography showed a hypovascular mass with fine neovascularity. These two findings of CT and arteriography were though to represent a probable malignant tumor but renal function of the patient decreased moderately. Surgical exploration was done and right renal masses were thought to be seen benign multilocular cysts without capsule. Simple excision of the wall of cysts and right adrenalectomy were performed. Pathological examinations showed multilocular cystic renal cell carcinoma and benign adrenal hyperplasia. Additionally partial nephrectomy was done. Surgical margin of the kidney was tumor free and postoperative course was uneventful. Prognosis of multiocular cystic renal cell carcinoma is good, therefore conservative surgery is recommended.

  8. Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Xinchao Wu

    2017-04-01

    Full Text Available Background/Aims: Renal cell carcinoma (RCC remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4 in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. Methods: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. Results: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. Conclusions: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.

  9. 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.

  10. Heteronemin, a Spongean Sesterterpene, Induces Cell Apoptosis and Autophagy in Human Renal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Szu-Ying Wu

    2015-01-01

    Full Text Available Heteronemin is a bioactive marine sesterterpene isolated from the sponge Hyrtios sp. Previous reports have shown that heteronemin possesses anticancer activity. Here, heteronemin displayed cytotoxic effects against three human cancer cell lines (A549, ACHN, and A498 and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 1.57 μM by MTT assay and a GI50 value of 0.77 μM by SRB assay. Heteronemin initiates apoptotic cell death by downregulating Bcl-2 and Bcl-xL and upregulating Bax, leading to the disruption of the mitochondrial membrane potential and the release of cytochrome c from the mitochondria. These effects were associated with the activation of caspase-3/caspase-8/caspase-9, followed by PARP cleavage. Furthermore, heteronemin inhibited the phosphorylation of AKT signaling pathway and ERK and activated p38 and JNK. The specific inhibition of the p38 pathway by SB203580 or p38 siRNA treatment reversed the heteronemin-induced cytotoxicity and apoptotic signaling. Heteronemin also induced autophagy in A498 cells, and treatment with chloroquine (autophagy inhibitor or SP600125 (JNK inhibitor inhibited autophagy and increased heteronemin-induced cytotoxicity and apoptotic signaling. Taken together, this study proposes a novel treatment paradigm in which the combination of heteronemin and autophagy inhibitors leads to enhanced RCC cell apoptosis.

  11. 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.

  12. 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...... before each line of therapy (favorable, F; intermediate, I; poor, P). Data were analyzed for 1516 patients, of whom 89% had clear cell histology. INTERVENTION: All included patients received targeted therapy for mRCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), time to treatment....... PATIENT SUMMARY: The pattern of treatment failure might help to predict what the next treatment should be for patients with metastatic renal cell carcinoma....

  13. 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.

  14. Sunitinib malate for the treatment of renal cell carcinoma.

    Science.gov (United States)

    Wood, Lori

    2012-06-01

    Over the past decade, a greater understanding into the molecular pathogenesis of renal cell carcinoma (RCC) has led to major advances in treatment options. Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor (TKI) that targets a number of receptors, including vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR). Sunitinib was one of the first targeted agents studied in metastatic RCC (mRCC) and is currently used worldwide in the management of mRCC. This drug evaluation addresses the preclinical and clinical development of sunitinib. It provides an in-depth discussion of the Phase II data that led to its approval in mRCC and the subsequent Phase III clinical trial comparing sunitinib to interferon-α. More recent data from the large international expanded access trial, in non-clear cell carcinoma patients, different dosing schedule studies and safety issues are also discussed. Finally, areas for the future use of sunitinib, including in the adjuvant setting, are reviewed. Since the FDA approved sunitinib for advanced RCC in January 2006, much more has been learned about its efficacy and tolerability. Over the past decade of its clinical use, it has become clear that expertise is required when prescribing sunitinib, in terms of maximizing dose, anticipating and managing side effects, and assessing responses. In the future, a better understanding of sunitinib's role compared with other VEGF TKIs and mTOR inhibitors, and in other roles such as the adjuvant setting or in non-clear cell pathology, will become evident.

  15. Tannic acid label indicates abnormal cell development coinciding with regeneration of renal tubules.

    Science.gov (United States)

    Minuth, Will W; Denk, Lucia

    2014-01-01

    Stem/progenitor cells are in the focus of research as a future therapeutic option to stimulate regeneration in diseased renal parenchyma. However, current data indicate that successful seeding of implanted stem/progenitor cells is prevented by harmful interstitial fluid and altered extracellular matrix. To find out possible parameters for cell adaptation, the present investigation was performed. Renal stem/progenitor cells were mounted in an artificial interstitium for perfusion culture. Exposure to chemically defined but CO2-independent culture media was tested during 13 days. Cell biological features were then analyzed by histochemistry, while structural details were investigated by transmission electron microscopy after conventional and improved fixation of specimens. Culture of renal stem/progenitor cells as well in Leibovitz's L-15 Medium as CO2 Independent Medium shows in fluorescence microscopy spatial development of numerous tubules. Specimens of both media fixed by conventional glutaraldehyde exhibit in electron microscopy a homogeneous cell population in developed tubules. In contrast, fixation by glutaraldehyde including tannic acid illuminates that dispersed dark marked cells of unknown function are present. The screening further demonstrates that the dark cell type does not comply with cells found in embryonic, maturing or matured renal parenchyma. The actual data show that development of abnormal cell features must be taken into account, when regeneration of renal tubules is simulated under in vitro conditions.

  16. [A case of renal cell carcinoma metastasizing to contralateral perirenal fat].

    Science.gov (United States)

    Uemura, Motohide; Nakagawa, Masahiro; Mukai, Masatoshi; Kanno, Nobufumi; Nishimura, Kensaku; Miyoshi, Susumu; Yoshida, Kyotaro; Kawano, Kiyoshi

    2003-08-01

    Extremely rarely renal cell carcinoma metastasizes to the contralateral perirenal fat. A 57-year-old male was admitted with macroscopic hematuria and lower left abdominal pain in December 1994. He was diagnosed with left renal cancer, and underwent left radical nephrectomy (RCC pT2, grade 1) in January 1995. Followup imaging studies showed a tumor arising from the right perirenal fat in 5 years. Tumor excision was performed in May 2000. Pathological findings revealed renal cell carcinoma growing in the fat, which had the same, pathology as the left renal cancer.

  17. Rare Case of Renal Cell Carcinoma with Mandibular Swelling as Primary Presentation

    Directory of Open Access Journals (Sweden)

    Aleena Jallu

    2013-01-01

    Full Text Available Introduction. Renal cell carcinoma accounts for approximately 3% of adult malignancies and 90–95% of neoplasms arising from the kidney. This disease is characterized by a lack of early warning signs, diverse clinical manifestations, and resistance to radiation and chemotherapy. Approximately one-third of patients with renal cell carcinoma have metastatic disease at initial presentation. Fifteen percent of patients with renal cell carcinoma are said to present with metastases in the head and neck region. Most of the metastases from RCC to the head and neck involve the thyroid gland. The head and neck are unusual sites for metastases, but skin, skeletal muscle, thyroid gland, nasal cavity and paranasal sinus metastases have been reported. Case Report. The following report describes a rare case where the patient presented with mandibular swelling of short duration as the primary complaint without any symptom or sign pertaining to urinary tract and was found to have renal cell carcinoma on further workup. Conclusion. Metastatic renal cell carcinoma is a diagnostic dilemma especially when there is no pointer historically towards renal cell carcinoma as was in our case. An unusual vascular osteolytic lesion in head and neck in a middle-aged person should be dealt with high index of suspicion with renal cell carcinoma at the back of the mind.

  18. Rare case of renal cell carcinoma with mandibular swelling as primary presentation.

    Science.gov (United States)

    Jallu, Aleena; Latoo, Manzoor; Pampori, Rafiq

    2013-01-01

    Introduction. Renal cell carcinoma accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. This disease is characterized by a lack of early warning signs, diverse clinical manifestations, and resistance to radiation and chemotherapy. Approximately one-third of patients with renal cell carcinoma have metastatic disease at initial presentation. Fifteen percent of patients with renal cell carcinoma are said to present with metastases in the head and neck region. Most of the metastases from RCC to the head and neck involve the thyroid gland. The head and neck are unusual sites for metastases, but skin, skeletal muscle, thyroid gland, nasal cavity and paranasal sinus metastases have been reported. Case Report. The following report describes a rare case where the patient presented with mandibular swelling of short duration as the primary complaint without any symptom or sign pertaining to urinary tract and was found to have renal cell carcinoma on further workup. Conclusion. Metastatic renal cell carcinoma is a diagnostic dilemma especially when there is no pointer historically towards renal cell carcinoma as was in our case. An unusual vascular osteolytic lesion in head and neck in a middle-aged person should be dealt with high index of suspicion with renal cell carcinoma at the back of the mind.

  19. 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.

  20. 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)

  1. A Predominant Oxidative Renal Metabolite of Empagliflozin in Male Mice Is Cytotoxic in Mouse Renal Tubular Cells but not Genotoxic.

    Science.gov (United States)

    Smith, James D; Huang, Zimei; Escobar, Patricia A; Foppiano, Pamela; Maw, Hlaing; Loging, William; Yu, Hongbin; Phillips, Jonathan A; Taub, Mitchell; Ku, Warren W

    In a previously reported CD-1 mouse 2-year carcinogenicity study with the sodium glucose cotransporter-2 inhibitor empagliflozin, an increased incidence of renal tubular adenomas and carcinomas was identified only in the male high-dose group. Follow-up investigative studies have shown that the renal tumors in male high-dose mice were preceded by a number of renal degenerative/regenerative findings. Prior cross-species in vitro metabolism studies using microsomes identified an oxidative metabolite (M466/2) predominantly formed in the male mouse kidney and which spontaneously degrades to a metabolite (M380/1) and reactive 4-OH crotonaldehyde (CTA). In order to further evaluate potential modes of action for empagliflozin-associated male mouse renal tumors, we report here a series of in vitro investigative toxicology studies conducted to evaluate the cytotoxic and genotoxic potential of empagliflozin and M466/2. To assess the cytotoxic potential of empagliflozin and M466/2, a primary mouse renal tubular epithelial (mRTE) cell model was used. In mRTE cells, M466/2-derived in vitro 4-OH CTA exposure was cytotoxic, while empagliflozin was not cytotoxic or mitogenic. Empagliflozin and M466/2 were not genotoxic, supporting an indirect mode of action for empagliflozin-associated male mouse renal tumorigenesis. In conclusion, these in vitro data show that M466/2-derived 4-OH CTA exposure is associated with cytotoxicity in renal tubule cells and may be involved in promoting compound-related in vivo renal metabolic stress and chronic low-level renal injury, in turn supporting a nongenotoxic mode of tumor pathogenesis specific to the male mouse.

  2. Risk factors for bone metastasis from renal cell cancer.

    Science.gov (United States)

    Chen, Xuan-Yin; Lan, Min; Zhou, Yang; Chen, Wen-Zhao; Hu, Dong; Liu, Jia-Ming; Huang, Shan-Hu; Liu, Zhi-Li; Zhang, Zhi-Hong

    2017-11-01

    The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. In this study, we investigate the correlation between diverse clinical factors and bone metastases secondary from renal cell cancer (RCC), and to identify potential risk factors for bone metastasis in newly diagnosed patients and those who have already received treatment. The clinical data of 372 patients with RCC were reviewed from January 2000 to August 2016. The correlations between age, gender, histopathologic types, alkaline phosphotase (ALP), CEA, AFP, CA-125, CA-153, CA-199, calcium, hemoglobin (HB) and bone metastases were analyzed. And the risk factors for bone metastases in RCC were identified by multivariate logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated by receiver operating characteristic (ROC) curve. The bone is the second to the lung as a distant metastasis target site in patients with RCC. Thirty eight individuals were identified with bone metastases. Of these patients, significantly higher levels of ALP, calcium, HB were found than those without bone metastasis (P 0.05, respectively). Multivariate logistic regression analysis indicated that ALP, calcium and HB were independent risk factors correlated with bone metastasis (P factors had comparable accuracy at predicting bone metastasis (AUC were 0.749, 0.633 and 0.665, respectively). The cutoff values of ALP, calcium and HB were 105.5 U/L, 2.615 mmol/L and 111.5 g/L, respectively. The sensitivities of them were 57.9%, 36.8% and 71.1% for predicting bone metastasis, with specificities of 83.5%, 95.2% and 65.3%, respectively. Based on our study, the concentrations of ALP, calcium and HB were potentially risk factors for bone metastasis in patients with RCC. For newly diagnosed patients, if the values of ALP>105.5 U/L, calcium>2.615 mmol/L and HB<111.5 g/L were detected, intensive monitoring and

  3. 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...... of the hypoxia regulatory network....

  4. Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo

    NARCIS (Netherlands)

    C.H.J. Lamers (Cor); S.C.L. Langeveld (Sabine); C.M. Groot-van Ruijven (Corrien); J.E.M.A. Debets (Reno); S. Sleijfer (Stefan); J.W. Gratama (Jan-Willem)

    2007-01-01

    textabstractAbstract BACKGROUND: We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)], and

  5. 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...

  6. 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.

  7. SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis.

    Science.gov (United States)

    Dong, Baijun; Gao, Yujing; Kang, Xunlei; Gao, Hongchang; Zhang, Jin; Guo, Hua; You, Mingjian J; Xue, Wei; Cheng, Jinke; Huang, Yiran

    2016-12-06

    Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC. Moreover, SENP1 knockdown in RCC4/VHL cells downregulated expression of key glycolytic enzymes under normoxic and hypoxic conditions and inhibited cell proliferation under hypoxic conditions, possibly due to ineffective deSUMOylation and stablization of Hif-1α related to the SENP-1 deficiency. Finally, SENP1 expression correlated positively with tumor pathological grade and was an indicator of poor overall survival and advanced tumor progression in ccRCC. Altered VHL gene function is found in 60-90% ccRCC cases of ccRCC, but therapies targeting VHL-related signaling pathways have been ineffective, spurring exploration of alternative pathological signaling events. Our results provide a possible mechanistic explanation for the role of SENP1 in the initiation and development of ccRCC with normal VHL activity, and identifies SENP1 as a potential treatment target for the disease.

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

    International Nuclear Information System (INIS)

    Morizane, Ryuji; Monkawa, Toshiaki; Itoh, Hiroshi

    2009-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Patterns of care for metastatic renal cell carcinoma in Australia.

    Science.gov (United States)

    Day, Daphne; Kanjanapan, Yada; Kwan, Edmond; Yip, Desmond; Lawrentschuk, Nathan; Andrews, Miles; Davis, Ian D; Azad, Arun A; Rosenthal, Mark; Wong, Shirley; Johnstone, Alice; Gibbs, Peter; Tran, Ben

    2015-10-01

    To examine the patterns of care and outcomes for metastatic renal cell carcinoma (mRCC) in Australia, where there are limited reimbursed treatment options. In particular, we aim to explore prescribing patterns for first-line systemic treatment, the practice of an initial watchful-waiting approach, and the use of systemic treatments in elderly patients. Patients with mRCC undergoing treatment between 2006 and 2012 were identified from four academic hospitals in Victoria and Australian Capital Territory. Demographic, clinicopathological, treatment, and survival data were recorded by chart review. Descriptive statistics were used to report findings. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test. The study was supported by a grant from Pfizer Australia. Our study identified 212 patients with mRCC for analysis. Patients were predominantly of clear cell histology (75%), Eastern Cooperative Oncology Group performance status 90 days before initiating treatment; these patients had a median OS of 56.3 months. Elderly patients (50 patients aged ≥70 years) were more likely to receive BSC alone than younger patients (46% vs 16%, P < 0.001). Of those who received systemic therapy, elderly patients were also more likely to have upfront dose reductions (30% vs 8%, P = 0.03). Our study of patients with mRCC treated in Australian centres showed that sunitinib was the most commonly prescribed systemic treatment between 2006 and 2012, associated with survival outcomes similar to pivotal studies. We also found that an initial watchful-waiting approach is commonly adopted without apparent detriment to survival. And finally, we found that age has an impact on the prescribing of systemic therapy. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  11. Novel concepts of antiangiogenic therapies in metastatic renal cell cancer.

    Science.gov (United States)

    Pichler, Renate; Heidegger, Isabel

    2017-01-01

    The era of antiangiogenic drugs targeting the vascular endothelial growth factor (VEGF) signaling pathway has become a mainstay in the treatment of metastatic renal cell carcinoma (mRCC), showing primary responses in 65-70% of patients. Nevertheless, most of those patients progress to angiogenesis inhibitors over time due to different modes of resistance (adaptive and intrinsic). Both in vitro and in vivo analyses provided evidence that PD-L1 upregulation in hypoxia conditions is dependent on hypoxia-inducible factor (HIF)-2alpha and is associated with an overexpression of VEGF. Thus, additional blockade of PD-L1 along with inhibition of angiogenesis pathways seems to represent a novel and innovative treatment concept in mRCC. In this short review, we provide an overview on ongoing phase III trials combining antiangiogenic therapies with checkpoint inhibitors in the first-line setting. Moreover, we critically analyze the impact of recently approved therapeutic antiangiogenic agents and checkpoint inhibitors after progression to first-generation tyrosine kinase inhibitors and their mode of action. In addition, response and resistance hypotheses and biomarkers to antiangiogenic therapy in clinical practice are critically discussed.

  12. 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 ...

  13. 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

  14. Functional significance of erythropoietin in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Morais Christudas

    2013-01-01

    Full Text Available Abstract 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. [Monitoring of metastatic renal cell carcinoma--standards and challenges].

    Science.gov (United States)

    Jäger, Elke

    2010-01-01

    The introduction of targeted therapies has led to a novel situation regarding monitoring of metastatic renal cell carcinoma (mRCC): patients treated with these new drugs have a significantly longer life expectancy than just a few years ago. In order to maximize the treatment benefit, new demands have come up on the assessment of tumor progression: timing and interpretation of imaging studies are crucial for optimal therapeutic management. Detailed knowledge of the new compounds' mode of action is important as it is different from that of classic cytotoxic drugs. The RECIST criteria constitute the standard for evaluation. Following recommendations made by the German Cancer Society's (DKG) interdisciplinary task force, targeted therapies should strive for a sufficient treatment duration in each line of therapy in order to achieve the best therapeutic outcome. Treatment is continued until clinical progression occurs. Assessing therapeutic efficacy with adequate imaging techniques 6-9 weeks after the beginning of therapy is recommended. Subsequent follow-up examinations should be repeated using identical imaging modalities every 2-3 months. For cyclically applied drugs such as Sunitinib, examinations should be carried out at identical time points within the treatment cycle. Copyright 2010 S. Karger AG, Basel.

  16. 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

  17. 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

  18. [Renal cell carcinoma in older and geriatric patients].

    Science.gov (United States)

    Wagener, N

    2017-08-01

    Renal cell carcinoma (RCC) is a disease of older humans. Due to increased detection of tumours by ultrasound and computed tomography, the number of incidentally diagnosed RCCs has increased. These tumours are usually smaller and of lower stage. Furthermore, there is an increase of older people in the population. Characteristics of tumour biology, prognosis, diagnostics and therapy of localized, advanced and metastatic RCC in old and geriatric patients are provided. Systematic literature review, analysis and discussion of original research articles and expert opinions. The surgical treatment of RCC in old and geriatric patients requires attention to increased morbidity and mortality. Active surveillance or ablations are alternatives to surgical treatment in localized RCC. Systemic therapy in metastatic tumours exhibit analogous efficacy with slightly worse toxicity. RCC in old and geriatric patients requires an adaptation of classic therapeutic strategies. Management should be adjusted individually to age and comorbidities. Efficacy, risk and toxicity of all therapeutic options should be considered. A multidisciplinary approach is important for diagnosis, assessment and therapy. Recommendations should be discussed with patients and their relatives according to the individual needs, and treatment decisions should be based on patient preferences wherever possible.

  19. 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.

  20. 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.

  1. Role of the ubiquitin proteasome system in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Corn Paul G

    2007-11-01

    Full Text Available Abstract Renal cell carcinoma (RCC accounts for approximately 2.6% of all cancers in the United States. While early stage disease is curable by surgery, the median survival of metastatic disease is only 13 months. In the last decade, there has been considerable progress in understanding the genetics of RCC. The VHL tumor suppressor gene is inactivated in the majority of RCC cases. The VHL protein (pVHL acts as an E3 ligase that targets HIF-1, the hypoxia inducible transcription factor, for degradation by the ubiquitin proteasome system (UPS. In RCC cases with mutant pVHL, HIF-1 is stabilized and aberrantly expressed in normoxia, leading to the activation of pro-survival genes such as vascular endothelial growth factor (VEGF. This review will focus on the defect in the UPS that underlies RCC and describe the development of novel therapies that target the UPS. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  2. 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.

  3. 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

  4. Smac-Mimetic–Induced Epithelial Cell Death Reduces the Growth of Renal Cysts

    Science.gov (United States)

    Fan, Lucy X.; Zhou, Xia; Sweeney, William E.; Wallace, Darren P.; Avner, Ellis D.; Grantham, Jared J.

    2013-01-01

    Past efforts to pharmacologically disrupt the development and growth of renal cystic lesions focused primarily on normalizing the activity of a specific signaling molecule, but the effects of stimulating apoptosis in the proliferating epithelial cells have not been well studied. Although benign, ADPKD renal cysts created by the sustained proliferation of epithelial cells resemble tumors, and malignant cell death can be achieved by cotreatment with TNF-α and a mimetic of second mitochondria-derived activator of caspase (Smac). Notably, TNF-α accumulates to high levels in ADPKD cyst fluid. Here, we report that an Smac-mimetic selectively induces TNF-α–dependent cystic renal epithelial cell death, leading to the removal of cystic epithelial cells from renal tissues and delaying cyst formation. In vitro, a Smac-mimetic (GT13072) induced the degradation of cIAP1 that is required but not sufficient for cell death. Cotreatment with TNF-α augmented the formation and activation of the RIPK1-dependent death complex and the degradation and cleavage of FLIP, an inhibitor of caspase-8, in renal cystic epithelial cells. This approach produced death specifically in Pkd1 mutant epithelial cells, with no effect on normal renal epithelial cells. Moreover, treatment with the Smac-mimetic slowed cyst and kidney enlargement and preserved renal function in two genetic strains of mice with Pkd1 mutations. Thus, our mechanistic data characterize an apoptotic pathway, activated by the selective synergy of an Smac-mimetic and TNF-α in renal cyst fluid, that attenuates cyst development, providing an innovative translational platform for the rational development of novel therapeutics for ADPKD. PMID:23990677

  5. Smac-mimetic-induced epithelial cell death reduces the growth of renal cysts.

    Science.gov (United States)

    Fan, Lucy X; Zhou, Xia; Sweeney, William E; Wallace, Darren P; Avner, Ellis D; Grantham, Jared J; Li, Xiaogang

    2013-12-01

    Past efforts to pharmacologically disrupt the development and growth of renal cystic lesions focused primarily on normalizing the activity of a specific signaling molecule, but the effects of stimulating apoptosis in the proliferating epithelial cells have not been well studied. Although benign, ADPKD renal cysts created by the sustained proliferation of epithelial cells resemble tumors, and malignant cell death can be achieved by cotreatment with TNF-α and a mimetic of second mitochondria-derived activator of caspase (Smac). Notably, TNF-α accumulates to high levels in ADPKD cyst fluid. Here, we report that an Smac-mimetic selectively induces TNF-α-dependent cystic renal epithelial cell death, leading to the removal of cystic epithelial cells from renal tissues and delaying cyst formation. In vitro, a Smac-mimetic (GT13072) induced the degradation of cIAP1 that is required but not sufficient for cell death. Cotreatment with TNF-α augmented the formation and activation of the RIPK1-dependent death complex and the degradation and cleavage of FLIP, an inhibitor of caspase-8, in renal cystic epithelial cells. This approach produced death specifically in Pkd1 mutant epithelial cells, with no effect on normal renal epithelial cells. Moreover, treatment with the Smac-mimetic slowed cyst and kidney enlargement and preserved renal function in two genetic strains of mice with Pkd1 mutations. Thus, our mechanistic data characterize an apoptotic pathway, activated by the selective synergy of an Smac-mimetic and TNF-α in renal cyst fluid, that attenuates cyst development, providing an innovative translational platform for the rational development of novel therapeutics for ADPKD.

  6. Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq.

    Science.gov (United States)

    Chen, Lihe; Lee, Jae Wook; Chou, Chung-Lin; Nair, Anil V; Battistone, Maria A; Păunescu, Teodor G; Merkulova, Maria; Breton, Sylvie; Verlander, Jill W; Wall, Susan M; Brown, Dennis; Burg, Maurice B; Knepper, Mark A

    2017-11-14

    Prior RNA sequencing (RNA-seq) studies have identified complete transcriptomes for most renal epithelial cell types. The exceptions are the cell types that make up the renal collecting duct, namely intercalated cells (ICs) and principal cells (PCs), which account for only a small fraction of the kidney mass, but play critical physiological roles in the regulation of blood pressure, extracellular fluid volume, and extracellular fluid composition. To enrich these cell types, we used FACS that employed well-established lectin cell surface markers for PCs and type B ICs, as well as a newly identified cell surface marker for type A ICs, c-Kit. Single-cell RNA-seq using the IC- and PC-enriched populations as input enabled identification of complete transcriptomes of A-ICs, B-ICs, and PCs. The data were used to create a freely accessible online gene-expression database for collecting duct cells. This database allowed identification of genes that are selectively expressed in each cell type, including cell-surface receptors, transcription factors, transporters, and secreted proteins. The analysis also identified a small fraction of hybrid cells expressing aquaporin-2 and anion exchanger 1 or pendrin transcripts. In many cases, mRNAs for receptors and their ligands were identified in different cells (e.g., Notch2 chiefly in PCs vs. Jag1 chiefly in ICs), suggesting signaling cross-talk among the three cell types. The identified patterns of gene expression among the three types of collecting duct cells provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.

  7. Lymphangitic Retroperitoneal Carcinomatosis Occurring From Metastatic Sarcomatoid Chromophobe Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Meghna Alimchandani

    2014-03-01

    Full Text Available A 45-year-old man with left renal mass underwent nephrectomy to reveal a 20-cm tumor diagnosed as sarcomatoid chromophobe renal cell carcinoma. Lymph node metastasis of chromophobe and sarcomatoid components, disseminated tumor in retroperitoneal fat, lymphatic vessels, and perirenal adipose tissue in lymphangitic carcinomatosis pattern were identified. Chromophobe epithelial cells were positive for epithelial membrane antigen, c-Kit, and cytokeratin 7; sarcomatoid cells were positive for CD10 and smooth muscle antigen with high proliferation index. Chromophobe epithelial cells had loss of heterozygosity in chromosomes 1p and 1q, whereas sarcomatoid cells had loss of heterozygosity in 3p, 1p, and 1q. In conclusion, sarcomatoid chromophobe renal cell carcinoma has aggressive biologic behavior and potential to metastasize in unusual patterns.

  8. New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy.

    Science.gov (United States)

    Zarrabi, Kevin; Fang, Chunhui; Wu, Shenhong

    2017-02-02

    Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

  9. New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy

    Directory of Open Access Journals (Sweden)

    Kevin Zarrabi

    2017-02-01

    Full Text Available Abstract Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.

  10. Rapid deterioration of preexisting renal insufficiency after autologous mesenchymal stem cell therapy

    Directory of Open Access Journals (Sweden)

    Jun-Seop Kim

    2017-06-01

    Full Text Available Administration of autologous mesenchymal stem cells (MSCs has been shown to improve renal function and histological findings in acute kidney injury (AKI models. However, its effects in chronic kidney disease (CKD are unclear, particularly in the clinical setting. Here, we report our experience with a CKD patient who was treated by intravenous infusion of autologous MSCs derived from adipose tissue in an unknown clinic outside of Korea. The renal function of the patient had been stable for several years before MSC administration. One week after the autologous MSC infusion, the preexisting renal insufficiency was rapidly aggravated without any other evidence of AKI. Hemodialysis was started 3 months after MSC administration. Renal biopsy findings at dialysis showed severe interstitial fibrosis and inflammatory cell infiltration, with a few cells expressing CD34 and CD117, 2 surface markers of stem cells. This case highlights the potential nephrotoxicity of autologous MSC therapy in CKD patients.

  11. 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.

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

    Science.gov (United States)

    Hereditary kidney cancer syndromes include von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Learn about the genetics, clinical manifestations, and management of these hereditary kidney cancer syndromes in this expert-reviewed summary.

  13. Stem Cell Factor Expression after Renal Ischemia Promotes Tubular Epithelial Survival

    NARCIS (Netherlands)

    Stokman, Geurt; Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J. D.; Weening, Jan J.; Leemans, Jaklien C.; Florquin, Sandrine

    2010-01-01

    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

  14. Clear Cell Renal Cell Carcinoma Metastatic to the Gynecologic Tract: A Clinicopathologic Analysis of 17 Cases.

    Science.gov (United States)

    Fadare, Oluwole; Desouki, Mohamed M; Gwin, Katja; Hanley, Krisztina Z; Jarboe, Elke A; Liang, Sharon X; Quick, Charles M; Rawish, Kojo R; Roma, Andres A; Zheng, Wenxin; Hecht, Jonathan L; Parkash, Vinita; Osunkoya, Adeboye O

    2017-11-14

    Clear cell renal cell carcinomas (CCRCC) rarely metastasizes to the gynecologic tract. In this study, we analyzed a multi-institutional data set to provide insights into the clinical, morphologic, and immunophenotypic features of this phenomenon. Seveteen metastatic CCRCC involving the gynecologic tract [ovary/fallopian tube (n=9), vulva (n=2), uterine corpus (n=3), cervix (n=2), uterine serosa (n=1)] were analyzed. Mean patient age was 62 yr (range: 45-79 yr). Most cases (15/17) presented as a recurrence 6 to 72 mo postnephrectomy, 1 case was concurrently diagnosed, and 1 case (a cervical metastasis) was diagnosed prenephrectomy. In 10 cases, metastases to other locations were identified within 6 wk of the gynecologic tract lesion. The adnexa were the most common site of metastases and the mean tumor size of adnexal metastases was 3.7 cm; in only 2 of 9 cases were metastases bilateral and only 1 had external surface nodules. The morphologic and immunohistochemical features of metastatic CCRCC were compared with those of 102 müllerian clear cell carcinomas (müllerian CCC: 49 endometrial, 53 ovarian). Although CCRCC and müllerian CCC displayed extensive morphologic overlap, a higher mitotic index and a higher frequency of an alveolar pattern were seen in CCRCC, whereas diffuse hobnail cells, hyaline globules, tubulocystic pattern, or any papillary pattern were more frequently seen in müllerian CCC. CA-IX, CD10, and renal cell carcinoma antigen were more frequently expressed in CCRCC than müllerian CCC, whereas Napsin-A, CK7, and p504S showed the reverse. PAX8 and HNF1β did not significantly distinguish between the 2 groups. In summary, gynecologic tract metastases most often occur as a relapse of a previously resected CCRCC, and these relapses may occur many years postnephrectomy. Gynecologic tract metastases are often accompanied by concurrent metastases to other organs. The gross pathology of metastatic CCRCC in the ovary may potentially overlap

  15. [Exogenous putrescine causes renal function impairment and cell apoptosis in rats].

    Science.gov (United States)

    Zhou, Yueping; Xiao, Nengkan; Rong, Xinzhou; Fan, Guicheng; Liu, Sirong

    2012-11-01

    To explore the effect of exogenous putrescine on renal function and cell apoptosis in rats. Ninety SD rats were randomized into control group (n=10), high-dose putrescine group (P1 group, n=40), and low-dose putrescine group (P2 group, n=40) with intraperitoneal injections of 2 ml of normal saline, 50 µg/g putrescine, and 25 µg/g putrescine, respectively. At 24, 48, 72 and 96 h after the injections, 10 rats from each group were sacrificed to examine serum Cr and BUN levels, histological changes in the kidneys, and renal cell apoptosis (TUNEL assay). The rats in the two putrescine- treated groups showed mild edema in some renal tissues without obvious necrosis. In P1 and P2 groups, serum Cr and BUN levels differed significantly at each time point of measurement (Pputrescine-treated groups showed gradually increased renal cell apoptosis with time, reaching the peak levels at 96 h and 48 h, respectively. The peak renal cell apoptosis rates in P1 [(24.78∓2.19)%] and P2 [(26.27∓2.13)%] group were significantly higher than the rate in the control group [(4.47∓0.33)%, Pputrescine can lead to renal function impairment and induce renal cell apoptosis in rats, and the severity of these changes appeared to be associated with the blood concentration of exogenous putrescine.

  16. High expression of HMGA2 predicts poor survival in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Na N

    2016-11-01

    Full Text Available Ning Na,1,* Tujie Si,2,* Zhengyu Huang,1,* Bin Miao,1 Liangqing Hong,1 Heng Li,1 Jiang Qiu,2 Jianguang Qiu3 1Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, 2Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, 3Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: High-mobility group AT-hook 2 (HMGA2 is involved in a wide spectrum of biological processes and is upregulated in several tumors, but its role in renal carcinoma remains unclear. The aim of this study was to examine the expression of HMGA2 and its relationship to the overall survival (OS of patients with non-metastatic clear cell renal cell carcinoma (ccRCC following surgery. The expression of HMGA2 was evaluated retrospectively by immunohistochemistry (IHC in 162 patients with ccRCC who underwent nephrectomy in 2003 and 2004. An IHC analysis revealed that HMGA2 was expressed in the nuclei of tumor cells in 146 (90.1% patients with ccRCC. The level of HMGA2 was positively correlated with tumor size, lymph node metastasis, and Fuhrman Grade. A Kaplan–Meier analysis with log-rank test found that patients with high HMGA2 expression had a poor outcome and that patients with low HMGA2 expression had better survival. Cox regression analysis showed that HMGA2 expression could serve as an independent prognostic factor for ccRCC patients. The efficacy of the following prognostic models was improved when HMGA2 expression was added: tumor node metastasis stage, UCLA Integrated Scoring System, Mayo Clinic stage, size, grade, and necrosis score. In summary, this study showed that HMGA2 expression is an independent prognostic factor for OS in patients with ccRCC. HMGA2 was found to be a valuable biomarker for ccRCC progression. Keywords: renal carcinoma, high-mobility group protein A

  17. Metastasis from renal cell carcinoma to thyroid presenting as rapidly growing neck mass

    OpenAIRE

    Mohammadi, Afshin; Toomatari, Seyed Babak Mosavi; Ghasemi-Rad, Mohammad

    2014-01-01

    INTRODUCTION: Renal cell carcinoma (RCC) is commonly known as the “internist's tumor” because of its unpredictable behavior. Metastasis to the thyroid gland is rarely found in clinical practice. PRESENTATION OF CASE: We report a rare case of non-thyroid malignancies NTM from renal cell carcinoma 1.5 years after radical nephrectomy in a 58-year-old man with a rapidly growing neck mass. DISCUSSION: Malignant melanoma, breast carcinoma, lung, and skin cancer are the most common sources of ...

  18. ''Hot spot'' on gallium-67-citrate scan in renal cell carcinoma. Clinicopathologic and biochemical correlation

    International Nuclear Information System (INIS)

    Kawamura, J.; Itoh, H.; Yoshida, O.; Fujita, T.; Torizuka, K.

    1984-01-01

    A frontal tomographic whole-body gallium-67-citrate scan was performed on 30 patients with renal cell carcinoma. Positive gallium uptake by the kidney in 20 patients (66.7%) correlated well with the clinicopathologically higher stage and grade of the tumor and with abnormal values in prognostic indexes in the blood. Thus, a negative gallium uptake may be indicative of an improved clinical course and longer survival in patients with renal cell carcinoma

  19. [A renal cell carcinoma metastasis to the contralateral perirenal fat : a case report].

    Science.gov (United States)

    Noguchi, Go; Makiyama, Kazuhide; Sano, Futoshi; Nakaigawa, Noboru; Yao, Masahiro; Kubota, Yoshinobu

    2011-07-01

    A 53-year-old woman was admitted with right lower abdominal pain in November 1993. Computed tomography (CT) revealed a right renal tumor, suspected to be a renal cancer. She underwent right radical nephrectomy in December 1993. The pathological diagnosis was clear cell carcinoma, pT2, grade 2. In May 2006, follow-up CT showed a tumor arising from the left perirenal fat. Laparoscopic tumor excision was performed in August 2006. The pathological diagnosis was metastatic clear cell carcinoma.

  20. Recognizing the Continuous Nature of Expression Heterogeneity and Clinical Outcomes in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Wei, Xiaona; Choudhury, Yukti; Lim, Weng Khong; Anema, John; Kahnoski, Richard J; Lane, Brian; Ludlow, John; Takahashi, Masayuki; Kanayama, Hiro-Omi; Belldegrun, Arie; Kim, Hyung L; Rogers, Craig; Nicol, David; Teh, Bin Tean; Tan, Min-Han

    2017-08-04

    Clear cell renal cell carcinoma (ccRCC) has been previously classified into putative discrete prognostic subtypes by gene expression profiling. To investigate the robustness of these proposed subtype classifications, we evaluated 12 public datasets, together with a new dataset of 265 ccRCC gene expression profiles. Consensus clustering showed unstable subtype and principal component analysis (PCA) showed a continuous spectrum both within and between datasets. Considering the lack of discrete delineation and continuous spectrum observed, we developed a continuous quantitative prognosis score (Continuous Linear Enhanced Assessment of RCC, or CLEAR score). Prognostic performance was evaluated in independent cohorts from The Cancer Genome Atlas (TCGA) (n = 414) and EMBL-EBI (n = 53), CLEAR score demonstrated both superior prognostic estimates and inverse correlation with anti-angiogenic tyrosine-kinase inhibition in comparison to previously proposed discrete subtyping classifications. Inverse correlation with high-dose interleukin-2 outcomes was also observed for the CLEAR score. Multiple somatic mutations (VHL, PBRM1, SETD2, KDM5C, TP53, BAP1, PTEN, MTOR) were associated with the CLEAR score. Application of the CLEAR score to independent expression profiling of intratumoral ccRCC regions demonstrated that average intertumoral heterogeneity exceeded intratumoral expression heterogeneity. Wider investigation of cancer biology using continuous approaches may yield insights into tumor heterogeneity; single cell analysis may provide a key foundation for this approach.

  1. 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...

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

    NARCIS (Netherlands)

    Sittig, S.P.; Kollgaard, T.; Gronbaek, K.; Idorn, M.; Hennenlotter, J.; Stenzl, A.; Gouttefangeas, C.; Straten, P. Thor

    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

  3. Ethnic variation of the histological subtypes of renal cell carcinoma ...

    African Journals Online (AJOL)

    E.V. Ezenwa

    Malays with the papillary cell subtype, and also in the Chinese population the highest mortality rate was found in cases with the papillary cell subtype (16.9%). Conclusion: The commonest histological subtype of RCC in each of the studied ethnic groups in Singapore is clear cell carcinoma. However, most of the cancer ...

  4. Biomolecular assessment of renal function in various types of surgical treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Popkov V.M.

    2017-03-01

    Full Text Available Objective: to assess the possibility of using the markers of acute kidney injury to predict the preoperative risk for the subsequent decline in glomerular filtration rate in different types of surgical treatment of renal cell carcinoma (RCC. Material and methods. 60 patients with histologically confirmed RCC T1-3M0N0 operated in the clinic of urology of Saratov State Medical University n.a. V. I. Razumovsky in the volume of nephrectomy or partial nephrectomy. Before surgery all patients underwent standard examination intended for patients with kidney tumors: ultrasound, MRI, excretory urography and dynamic renoscintigraphy, the perioperative values of serum creatinine and glomerular filtration rate were determined. Using the method of immuno-enzymatic analysis the concentrations of excreted with the urine NGAL and IL-18 in serum samples at the preoperative stage, after 5 days and after 1 month of postoperative follow-up were investigated. Differences in clinical data and clinical variables were compared by using Spearman rank correlations and t-test. Results. The determined parameters of acute kidney injury markers IL-18 and NGAL in the early postoperative period were increased in patients after open nephrectomy. Moreover, the correlation analysis according to the Spearman method revealed a strong significant correlation between the preoperative levels of IL-18 and GFR after surgery (r=1; p<0.05. Conclusion. Laparoscopic resection of RCC is the method of choice for surgical treatment of RCC. As a predictor of adverse prognosis, the level of IL-18 in serum may be used. Its increase correlates with a decline in renal function in the postoperative period, and according to some reports, IL-18 also is an independent predictor of adverse prognosis in patients with a localized RCC.

  5. 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 ...

  6. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma - A clinical, phase 1/2 trial

    DEFF Research Database (Denmark)

    Berntsen, A.; Trepiakas, R.; Wenandy, L.

    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...

  7. RON kinase inhibition reduces renal endothelial injury in sickle cell disease mice.

    Science.gov (United States)

    Khaibullina, Alfia; Adjei, Elena A; Afangbedji, Nowah; Ivanov, Andrey; Kumari, Namita; Almeida, Luis E F; Quezado, Zenaide M N; Nekhai, Sergei; Jerebtsova, Marina

    2018-03-08

    Sickle cell disease patients are at increased risk of developing a chronic kidney disease. Endothelial dysfunction and inflammation associated with hemolysis lead to vasculopathy and contribute to the development of renal disease. Here we used a Townes sickle cell disease mouse model to examine renal endothelial injury. Renal disease in Townes mice was associated with glomerular hypertrophy, capillary dilation and congestion, and significant endothelial injury. We also detected substantial renal macrophage infiltration, and accumulation of macrophage stimulating protein 1 in glomerular capillary. Treatment of human cultured macrophages with hemin or red blood cell lysates significantly increased expression of macrophage membrane-associated protease that might cleave and activate circulating macrophage stimulating protein 1 precursor. Macrophage stimulating protein 1 binds to and activates RON kinase, a cell surface receptor tyrosine kinase. In cultured human renal glomerular endothelial cells, macrophage stimulating protein 1 induced RON downstream signaling, resulting in increased phosphorylation of ERK and AKT kinases, expression Von Willebrand factor, increased cell motility, and re-organization of F-actin. Specificity of macrophage stimulating protein 1 function was confirmed by treatment with RON kinase inhibitor BMS-777607 that significantly reduced downstream signaling. Moreover, treatment of sickle cell mice with BMS-777607 significantly reduced glomerular hypertrophy, capillary dilation and congestion, and endothelial injury. Taken together, our findings demonstrated that RON kinase is involved in the induction of renal endothelial injury in sickle cell mice. Inhibition of RON kinase activation may provide a novel approach for prevention of renal disease development in sickle cell disease. Copyright © 2018, Ferrata Storti Foundation.

  8. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

    Science.gov (United States)

    Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley; Gulati, Sakshi; Bates, Paul A; Stamp, Gordon; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Futreal, P Andrew; Stewart, Aengus; Swanton, Charles

    2015-01-01

    Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development. PMID:24487277

  9. 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.

  10. Mesenchymal Stromal Cells Epithelial Transition Induced by Renal Tubular Cells-Derived Extracellular Vesicles.

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    Giulia Chiabotto

    Full Text Available Mesenchymal-epithelial interactions play an important role in renal tubular morphogenesis and in maintaining the structure of the kidney. The aim of this study was to investigate whether extracellular vesicles (EVs produced by human renal proximal tubular epithelial cells (RPTECs may induce mesenchymal-epithelial transition of bone marrow-derived mesenchymal stromal cells (MSCs. To test this hypothesis, we characterized the phenotype and the RNA content of EVs and we evaluated the in vitro uptake and activity of EVs on MSCs. MicroRNA (miRNA analysis suggested the possible implication of the miR-200 family carried by EVs in the epithelial commitment of MSCs. Bone marrow-derived MSCs were incubated with EVs, or RPTEC-derived total conditioned medium, or conditioned medium depleted of EVs. As a positive control, MSCs were co-cultured in a transwell system with RPTECs. Epithelial commitment of MSCs was assessed by real time PCR and by immunofluorescence analysis of cellular expression of specific mesenchymal and epithelial markers. After one week of incubation with EVs and total conditioned medium, we observed mesenchymal-epithelial transition in MSCs. Stimulation with conditioned medium depleted of EVs did not induce any change in mesenchymal and epithelial gene expression. Since EVs were found to contain the miR-200 family, we transfected MSCs using synthetic miR-200 mimics. After one week of transfection, mesenchymal-epithelial transition was induced in MSCs. In conclusion, miR-200 carrying EVs released from RPTECs induce the epithelial commitment of MSCs that may contribute to their regenerative potential. Based on experiments of MSC transfection with miR-200 mimics, we suggested that the miR-200 family may be involved in mesenchymal-epithelial transition of MSCs.

  11. Expression of minichromosome maintenance genes in renal cell carcinoma

    Science.gov (United States)

    Neves, Henrique; Xing, Jinchun; Ye, Youxin; Lin, Ying; Zhuang, Guohong; Zhang, Shu-Dong; Huang, Jiyi; Kwok, Hang Fai

    2017-01-01

    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 disease-free survival. Importantly, we also demonstrated that overexpression of MCM genes is an independent predictor for survival in RCC patients. Our results suggest that MCM2–7 genes may be an important prognostic marker for patients with RCC. PMID:29180899

  12. Surgical treatment of renal-cell carcinoma in elderly people.

    Science.gov (United States)

    Rodríguez-Covarrubias, F; Rivera-Ramirez, J A; Gabilondo-Pliego, B; Castillejos-Molina, R A; Sotomayor, M; Feria-Bernal, G; Gabilondo-Navarro, F

    2016-01-01

    To describe the oncological characteristics and evolution of patients 65 years or older who underwent surgery for renal-cell carcinoma (RCC). We reviewed our prospectively maintained database of patients with RCC treated surgically. Those ≥ 65 years old were selected. We analyzed clinical and pathological characteristics as well as oncological and functional outcomes. Overall survival (OS) was estimated with the Kaplan-Meier method. Multivariate Cox-proportional hazards model was used to determine predictors of OS. A total of 156 elderly patients with mean age 72.0±5.5 years (range 65-92) and median follow-up of 33 months were included. Surgical approach was open radical nephrectomy in 114 (73.5%), laparoscopic radical nephrectomy in 13 (8.4%), open partial nephrectomy in 23 (14.2%) and laparoscopic partial nephrectomy in 6 (3.9%). Pathological stage was: Stage I, 71 (45.5%); Stage II, 27 (17.3%); Stage III, 48 (30.8%); and Stage IV, 10 (6.4%). Lastly, 51 (32.6%) patients died, 22 (43.1%) from cancer. The 5-year OS according to pathological stage was 77.6%, 71.9%, 45.1% and 11.7% for stage I, II, III and IV, respectively (P<.001). On multivariate analysis, pathological stage independently predicted OS (HR 1.96, 95% CI [1.36-2.84], P=.0003). The surgical management of RCC appears to be safe in properly selected patients 65 years or older. Pathological stage predicts survival in this population. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Gene expression profiling predicts survival in conventional renal cell carcinoma.

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    Hongjuan Zhao

    2006-01-01

    Full Text Available BACKGROUND: Conventional renal cell carcinoma (cRCC accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival. METHODS AND FINDINGS: Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001. In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001. CONCLUSIONS: cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.

  14. Gene Expression Profiling Predicts Survival in Conventional Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Conventional renal cell carcinoma (cRCC accounts for most of the deaths due to kidney cancer. Tumor stage, grade, and patient performance status are used currently to predict survival after surgery. Our goal was to identify gene expression features, using comprehensive gene expression profiling, that correlate with survival. METHODS AND FINDINGS: Gene expression profiles were determined in 177 primary cRCCs using DNA microarrays. Unsupervised hierarchical clustering analysis segregated cRCC into five gene expression subgroups. Expression subgroup was correlated with survival in long-term follow-up and was independent of grade, stage, and performance status. The tumors were then divided evenly into training and test sets that were balanced for grade, stage, performance status, and length of follow-up. A semisupervised learning algorithm (supervised principal components analysis was applied to identify transcripts whose expression was associated with survival in the training set, and the performance of this gene expression-based survival predictor was assessed using the test set. With this method, we identified 259 genes that accurately predicted disease-specific survival among patients in the independent validation group (p < 0.001. In multivariate analysis, the gene expression predictor was a strong predictor of survival independent of tumor stage, grade, and performance status (p < 0.001. CONCLUSIONS: cRCC displays molecular heterogeneity and can be separated into gene expression subgroups that correlate with survival after surgery. We have identified a set of 259 genes that predict survival after surgery independent of clinical prognostic factors.

  15. [A Case of Renal Cell Carcinoma in a Crossed Fused Ectopic Kidney Treated with Partial Nephrectomy].

    Science.gov (United States)

    Okada, Manabu; Maehana, Takeshi; Tanaka, Toshiaki; Kitamura, Hiroshi; Masumori, Naoya

    2017-01-01

    A 76-year-old man came to the department of gastrointestinal medicine with lower left abdominal discomfort and constipation. A crossed fused ectopic kidney with a renal tumor in the left upper pole of the kidney was detected by computed tomography. We performed left partial nephrectomy safely in spite of the complicated shape and complexity of the blood vessels. The pathological diagnosis was clear cell renal cell carcinoma, pT3a, with a negative surgical margin. After surgery, renal function was well preserved.

  16. Adrenal and renal corticomedullary junction iron deposition in red cell aplasia

    Energy Technology Data Exchange (ETDEWEB)

    Rakow-Penner, Rebecca; Vasanawala, Shreyas [Stanford University School of Medicine, Department of Radiology, Stanford, CA (United States); Glader, Bert [Stanford University School of Medicine, Department of Pediatric Hematology and Oncology, Stanford, CA (United States); Yu, Huanzhou [Global MR Applied Science Lab, GE Healthcare, Menlo Park, CA (United States)

    2010-12-15

    Iron deposition can occur in the kidneys as a result of hemolysis or extensive iron overload from transfusions. With T2* MRI, renal iron deposition can be visualized. In this report, renal corticomedullary junction iron deposition is noted using T2* MRI in a boy with red cell aplasia. The renal corticomedullary junction iron deposition is an indication of the severity of his iron overload. This is an unusual finding and brings clinical attention to the boy's renal function for further evaluation. (orig.)

  17. 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.

  18. Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation.

    Science.gov (United States)

    Grange, Cristina; Tapparo, Marta; Tritta, Stefania; Deregibus, Maria Chiara; Battaglia, Antonino; Gontero, Paolo; Frea, Bruno; Camussi, Giovanni

    2015-12-24

    Tumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105(+) CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105(-) TCs) and their EVs. Maturation of monocyte-derived DCs was studied in presence of CD105(+) CSCs and CD105(-) TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors. The results obtained demonstrate that both CD105(+) CSCs and CD105(-) TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105(+) CSCs was significantly greater than that of CD105(-) TCs. EVs derived from CD105(+) CSCs and in less extent, those derived from CD105(-) TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation. In conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G.

  19. Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio [Jichi Medical School, Division of Environmental Medicine, Center for Community Medicine, Tochigi (Japan); Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST), Saitama (Japan)

    2006-10-15

    The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production. (orig.)

  20. [Laparoscopic resection of the transplanted kidney for renal cell carcinoma T1N0M0].

    Science.gov (United States)

    Vtorenko, V I; Trushkin, R N; Lubennikov, A E; Kolesnikov, N O

    2017-04-01

    Laparoscopic resection of the transplanted kidney has been very rarely reported in the literature. On the one hand, this is due to the extremely low incidence of tumors of renal transplants. On the other hand, these patients are usually managed by open surgery due to difficulties in laparoscopic resection because of the scar tissue in the kidney area. Other options, though rarely performed, are cryosurgery and radiofrequency ablation of the tumor. In this article we report our own experience with a patient who underwent laparoscopic resection of renal transplant for renal cell carcinoma T1aN0M0 19 years after kidney transplantation. The tumor sized 27 cm was found incidentally by routine ultrasound. The operative time was 115 minutes, the renal ischemia time - 28 min. No intra- and postoperative complications were observed. Histological examination revealed renal cell carcinoma, surgical margins were negative. The patient was discharged on the 7th day after the surgery, no graft dysfunction was observed.

  1. 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 m...

  2. Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma

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    Qing Zhang

    2017-01-01

    Full Text Available The chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. We developed an epidermal growth factor- (EGFR- specific third-generation CAR. NK-92 cells were modified with the CAR by lentivirus infection. The specific killing ability of the CAR-modified NK-92 cells (CAR-NK-92 against renal cell carcinoma (RCC cell lines was confirmed in vitro. The synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells were investigated in vitro and in vivo. Our results showed that the CAR-NK-92 cells lyse RCC cells in an EGFR-specific manner. Treatment with cabozantinib could increase EGFR and decrease PD-L1 membrane surface expression in RCC cells and enhance the killing ability of CAR-NK-92 cells against the RCC cells in vitro. Furthermore, the CAR-NK-92 cells show synergistic therapeutic efficacy with cabozantinib against human RCC xenograft models. Our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.

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

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    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.

  4. Reference genes for gene expression analysis by real-time reverse transcription polymerase chain reaction of renal cell carcinoma

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Pedersen, Shona; Kristensen, Søren Risom

    2011-01-01

    Differentiation between malignant renal cell carcinoma and benign oncocytoma is of great importance to choose the optimal treatment. Accurate preoperative diagnosis of renal tumor is therefore crucial; however, existing imaging techniques and histologic examinations are incapable of providing an ...

  5. GSTM1 genotype is an independent prognostic factor in clear cell renal cell carcinoma.

    Science.gov (United States)

    Coric, Vesna M; Simic, Tatjana P; Pekmezovic, Tatjana D; Basta-Jovanovic, Gordana M; Savic-Radojevic, Ana R; Radojevic-Skodric, Sanja M; Matic, Marija G; Suvakov, Sonja R; Dragicevic, Dejan P; Radic, Tanja M; Dzamic, Zoran M; Pljesa-Ercegovac, Marija S

    2017-06-01

    Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC). GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot. We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype (Prisk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1-genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

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    Min Jee Park

    2015-01-01

    Full Text Available Background: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2 in tumorigenesis or progression of renal cell carcinoma (RCC. The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs. Methods: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0, mild (1+, moderate (2+, and strong (3+. Results: TG2 staining intensity was negative in 8.5% of CCRCC (n=54, 1+ in 32.6% (n=208, 2+ in 50.5% (n=322, and 3+ in 8.5% (n=54. Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011, high T category (p=.049, metastasis (p=.043 and male sex (p<.001 but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively. On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054. Conclusions: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

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

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    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

  8. 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.

  9. Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient

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    Ibrahim Azar

    2017-01-01

    Full Text Available Sunitinib, a multitargeted tyrosine Kkinase inhibitor (TKI, is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS, and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN, in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF by either TKI (sunitinib and sorafenib or antibodies (bevacizumab suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

  10. Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

    Science.gov (United States)

    Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

    2017-01-01

    Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

  11. 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...

  12. 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.

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

    Science.gov (United States)

    Li, Shujue; Wu, Wenqi; Wu, Wenzheng; Duan, Xiaolu; Kong, Zhenzhen; Zeng, Guohua

    2016-01-01

    The interactions between calcium oxalate monohydrate (COM) crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry. Dedifferentiated MDCK cells induced by transforming growth factor β1 (TGF-β1) shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3β/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion. COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3β/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis. © 2016 The Author(s) Published by S. Karger AG, Basel.

  14. Solitary parotid metastasis 8 years after a nephrectomy for renal cell carcinoma

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    Faiz Hussain

    2016-09-01

    Full Text Available Renal cell carcinoma is a common cancer, known for its aggressive behavior and ability to metastasize nearly every organ system in the body. While the cancer commonly spreads to a select few organs and metastasis usually develops within 5 years of diagnosis, there have been numerous case reports of atypical sites of metastasis and cases of relapse up to decades after treatment. We present a case a 65-year-old male who presented with right preauricular swelling 8 years after the initial diagnosis and right nephrectomy for clear cell renal cell cancer. We take a look at previous case reports with similar presentations.

  15. MicroRNA-141 is downregulated in human renal cell carcinoma and regulates cell survival by targeting CDC25B

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    Yu XY

    2013-04-01

    Full Text Available Xiu-yue Yu, Zhe Zhang, Jiao Liu, Bo Zhan, Chui-ze Kong Department of Urology, the First Hospital of China Medical University, Shenyang, People’s Republic of China Background/objective: MicroRNAs (miRNAs are small noncoding RNAs (ribonucleic acids, approximately 22 nucleotides in length, that function as regulators of gene expression. Dysregulation of miRNAs has been associated with the initiation and progression of oncogenesis in humans. The cell division cycle (CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. Methods: Using miRNA target prediction software, we found that miR-141 could target the 3´ untranslated region (3´UTR sequence of CDC25B. To shed light on the role of miR-141 in renal cell carcinogenesis, the expression of miR-141 was examined by real-time polymerase chain reaction (RT-PCR in renal cell carcinoma and normal tissues. The impact of miR-141 re-expression on 769-P cells was analyzed using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and colony-forming assay. A luciferase reporter assay was applied to prove the functionality of the miR-141 binding site. Results: miR-141 is significantly downregulated in renal cell carcinoma. miR-141 re-expression suppressed cell growth in 769-P cells. Luciferase expression from a reporter vector containing the CDC25B-3'UTR was decreased when this construct was transfected with miR-141 in 769-P cells. The overexpression of miR-141 suppressed the endogenous CDC25B protein level in 769-P cells. Conclusion: For the first time, we demonstrated that CDC25B is a direct target of miR-141 in renal cell carcinoma. The transcriptional loss of miR-141 and the resultant increase in CDC25B expression facilitates increased genomic instability at an early stage of renal cell carcinoma development. Keywords: carcinogenesis, 769-P, target, Micro

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

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    Maria R. Ambrosio

    2015-01-01

    Full Text Available 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.

  17. Expression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients.

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    Peio Errarte

    Full Text Available The discovery of the intrarenal renin-angiotensin system (iRAS, which regulates angiogenesis, cell differentiation and proliferation, has opened new perspectives in the knowledge of kidney carcinogenesis. In this study we analyzed the immunohistochemical expression and fluorimetric activity of four key peptidases of iRAS in tumor tissue (n = 144 and serum samples (n = 128 from patients with renal neoplasms. Neutral endopeptidase (NEP/CD10, Angiotensin-converting enzyme-2 (ACE2, and aminopeptidase A (APA were expressed in tumor cells whilst Angiotensin-converting enzyme (ACE was expressed in the endothelial cells of intratumor blood vessels. The expression of ACE, ACE2 and NEP/CD10 was highest in clear cell renal cell carcinoma (CCRCC and papillary renal cell carcinoma (PRCC. The expression of these enzymes correlated with CCRCC aggressiveness. In addition, NEP/CD10 correlated with 15-year overall survival. On the other hand, APA expression was decreased in CCRCC with higher grade and stage. The loss of expression of APA independently correlated with a worse 15-year overall survival. Serum activity of ACE2, NEP/CD10 and APA was significantly higher in renal tumor patients than in healthy subjects. Serum ACE activity was lower in high grade and metastatic CCRCC patients, and NEP/CD10 activity was negatively correlated with UISS (UCLA Integrated Staging System and SSIGN (Mayo Clinic stage, size, grade and necrosis model scores and with overall survival of CCRCC patients. These results suggest a metabolic imbalance of iRAS in renal tumors. This finding should be taken into account in the search of new diagnostic, prognostic and therapeutic tools for this disease.

  18. 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

  19. 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

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

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    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.

  1. 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.

  2. Characterization of the Interaction of Staphylococcal Entertoxin B with CD1d Expressed in Human Renal Proximal Tubule Epithelial Cells

    Science.gov (United States)

    2015-02-04

    staphylococcal entertoxin B with CD1d expressed in human renal proxiaml tubule epithelial cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...conjugation between SEB and CD1d expressed on human renal proximal tubule epithelial cells (RPTEC) was further established by selective inhibition of...the non-human primate study reporting ~70% accumulation of SEB in the renal proximal tubule epithelial cells (RPTECs) within 90 mi- nutes of aerosol

  3. Food groups and renal cell carcinoma: results from a case-control study.

    Science.gov (United States)

    Grieb, Suzanne M Dolwick; Theis, Ryan P; Burr, Deborah; Benardot, Dan; Siddiqui, Tariq; Asal, Nabih R

    2009-04-01

    The role of diet in renal cell carcinoma risk has been inconclusive. This study uses an integrative approach to assess the role of food groups and food items in renal cell carcinoma risk. A case-control study was conducted from 2003-2006. Incident cases (n=335) were identified from hospital records and the Florida cancer registry, and population controls (n=337) frequency matched by age (+/-5 years), sex, and race were identified through random-digit dialing. Eating habits were assessed through the use of the 70-item Block food frequency questionnaire. Odds ratios (ORs), 95% confidence intervals (CIs), and tests for trends were calculated using logistic regression, controlled for age, sex, race, income, body mass index, and pack-years of smoking. Decreased renal cell carcinoma risk was observed among the total sample and for men for vegetable consumption (all subjects: OR 0.56, 95% CI 0.35, 0.88; men: OR 0.49, 95% CI 0.25, 0.96) but not for fruit consumption. Tomato consumption decreased renal cell carcinoma risk for the total population and for men (all subjects: OR 0.50, 95% CI 0.31, 0.81; men: OR 0.47, 95% CI 0.24, 0.95). Increased risk of renal cell carcinoma was observed among all subjects and among women with increased consumption of red meat (all subjects: OR 4.43, 95% CI 2.02, 9.75; women: OR 3.04, 95% CI 1.60, 5.79). White bread consumption increased renal cell carcinoma risk among women only (OR 3.05, 95% CI 1.50, 6.20), as did total dairy consumption (OR 2.36, 95% CI 1.21, 4.60). The protective role of vegetables and the increased risk of renal cell carcinoma with meat consumption are supported. The protective role of fruits is not. Novel findings include the increased risk of renal cell carcinoma with white bread and white potato consumption and the decreased risk of renal cell carcinoma with tomato consumption.

  4. Dendritic-cell-based immunotherapy evokes potent anti-tumor immune responses in CD105+ human renal cancer stem cells.

    Science.gov (United States)

    Zhang, Xiao-Fei; Weng, De-Sheng; Pan, Ke; Zhou, Zi-Qi; Pan, Qiu-Zhong; Zhao, Jing-Jing; Tang, Yan; Jiang, Shan-Shan; Chen, Chang-Long; Li, Yong-Qiang; Zhang, Hong-Xia; Chang, Alfred E; Wicha, Max S; Zeng, Yi-Xin; Li, Qiao; Xia, Jian-Chuan

    2017-11-01

    Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified "stem-like" characteristics of CD105+ cells in two human RCC cell lines: A498 and SK-RC-39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC-based immunotherapy for human RCC. © 2017 Wiley Periodicals, Inc.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

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

    Science.gov (United States)

    ... error that occurs as DNA copies itself during cell division. FH gene mutations may interfere with the enzyme's role in the citric acid cycle, resulting in a buildup of fumarate. Researchers believe ...

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

    African Journals Online (AJOL)

    calyceal system), angiography (may show hypovascular tumour) and cytology of the urine which may detect malignant cells. Nephrectomy for non-me- tastasized tumours, with removal of the retroperitoneal nodes, is usually the treatment of choice.

  12. Synchronous Oligometastatic Non-Small Cell Lung Cancer and Isolated Renal Cell Carcinoma: A Case Report and Literature Review.

    Science.gov (United States)

    Nguyen, Timothy K; Louie, Alexander V

    2015-10-27

    A 58-year-old gentleman presenting with a progressive headache, visual disturbance, decreased appetite, and weight loss was found to have a localized clear cell carcinoma of the kidney and synchronous Stage IV non-small cell lung cancer with a solitary brain metastasis. This case illustrates the challenges in distinguishing between primary and metastatic disease in a patient with both renal cell carcinoma and lung cancer. We highlight the uncertainties in the diagnosis and management of this unique clinical scenario and the potential implications on prognosis.

  13. Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically.

    Science.gov (United States)

    Vilaseca, Antoni; Nguyen, Daniel P; Vertosick, Emily A; Corradi, Renato B; Musquera, Mireia; Pérez, Meritxell; Fossati, Nicola; Sjoberg, Daniel D; Farré, Ramon; Almendros, Isaac; Montserrat, Josep M; Benfante, Nicole E; Hakimi, A Ari; Skanderup, Anders J; Russo, Paul; Alcaraz, Antonio; Touijer, Karim A

    2017-01-01

    To assess the association between obstructive sleep apnea (OSA) and Fuhrman grade in patients with clear cell renal cell carcinoma (ccRCC). As secondary endpoints, we studied its association with tumor size, metastasis-free survival (MFS) and cancer-specific survival (CSS). We reviewed the databases of two tertiary care centers, identifying 2579 patients who underwent partial or radical nephrectomy for ccRCC between 1991 and 2014. Descriptive statistics were used to compare pathologic variables between patients with and without OSA. Linear and logistic regression models were used to assess the association of OSA with Fuhrman grade and tumor size. A Cox proportional hazards model was used to determine OSA association with MFS and CSS. A pathway analysis was performed on a cohort with available gene expression data. In total, 172 patients (7 %) had self-reported OSA at diagnosis. More patients with OSA had high Fuhrman grade compared to those without OSA [51 vs. 38 %; 13 % risk difference; 95 % confidence interval (CI), 5-20 %; p = 0.003]. On multivariable analysis, the association remained significant (OR 1.41; 95 % CI 1.00-1.99; p = 0.048). OSA was not associated with tumor size (p > 0.5), MFS (p = 0.5) or CSS (p = 0.4). A trend toward vascular endothelial growth factor pathway enrichment was seen in OSA patients (p = 0.08). OSA is associated with high Fuhrman grade in patients undergoing surgery for ccRCC. Pending validation of this novel finding in further prospective studies, it could help shape future research to better understand etiological mechanisms associated.

  14. [Effects of SIPL1 screened by suppression subtractive hybridization (SSH) on biological function and drug resistance of renal cell carcinoma cells].

    Science.gov (United States)

    Li, Chun-yan; Yao, An-mei; Chang, Xiao-ning; Guo, Ya-huan; Xu, Rui

    2013-12-01

    To screen the differentially expressed genes in human renal clear-cell carcinoma (RCC) cells using suppression subtractive hybridization (SSH), and to explore their biological function and underlying mechanism in RCC cells. Total RNAs were extracted from human renal clear-cell carcinoma cell line RLC-310 and human normal renal cell line HK-2 cells, and SSH technology was used to construct a RCC cell library of differential expression genes and to screen the most differentially expressed genes. RNA interference vector was constructed to silence the expression of the differentially expressed gene SIPL1 in human renal cell lines RLC-310 and GRC-1. Proliferation index was estimated by cell counting, MTT and tumor xenograft assay. Cell cycle analysis was performed using fluorescence activated cell sorting. Drug resistance potential to adriamycin was assessed by MTT. A subtractive cDNA library of highly expressed genes in the RCC cells was constructed and 12 differentially expressed genes were screened from the subtractive library, in which SIPL1 was the most differently expressed gene in the RCC cell line. SIPL1 overexpression in the RCC cells and clinical samples was confirmed by RT-PCR and Western blot analyses. The shRNA expression plasmid targeting to SIPL1 gene was constructed and transfected into RLC-310 and GRC-1 cells, resulting in downregulation of SIPL1. SIPL1 knockdown inhibited the cell proliferation (P SSH technology. SIPL1 functions as an oncogene in RCC, and may become a novel molecular target for RCC diagnosis and therapy.

  15. Induction of trismus by sunitinib and pazopanib in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ridhima Iyer

    2017-01-01

    Full Text Available Tyrosine kinase inhibitors sunitinib and pazopanib are used as first-line agents in the treatment of metastatic renal cell carcinoma. Treatment-related toxicities have been described with both these drugs. This report describes a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is, to the best of our knowledge, the first such case to be reported.

  16. An atypical case of dermatomyositis associated with chromophobe renal cell carcinoma.

    Science.gov (United States)

    George, Michael David; Lahouti, Arash H; Christopher-Stine, Lisa

    2016-01-19

    Dermatomyositis and polymyositis are the major idiopathic inflammatory myopathies in adults. They are associated with an elevated risk of malignancy. However, renal tumours have rarely been described in dermatomyositis patients. We report the case of a 27-year-old Caucasian man with chromophobe renal cell cancer (ChRCC) and antinuclear matrix protein (NXP-2)-associated dermatomyositis. To the best of our knowledge, there are no previous reports of ChRCC presenting with dermatomyositis. 2016 BMJ Publishing Group Ltd.

  17. Tip cells act as dynamic cellular anchors in the morphogenesis of looped renal tubules in Drosophila.

    Science.gov (United States)

    Weavers, Helen; Skaer, Helen

    2013-11-11

    Tissue morphogenesis involves both the sculpting of tissue shape and the positioning of tissues relative to one another in the body. Using the renal tubules of Drosophila, we show that a specific distal tubule cell regulates both tissue architecture and position in the body cavity. Focusing on the anterior tubules, we demonstrate that tip cells make transient contacts with alary muscles at abdominal segment boundaries, moving progressively forward as convergent extension movements lengthen the tubule. Tip cell anchorage antagonizes forward-directed, TGF-β-guided tubule elongation, thereby ensuring the looped morphology characteristic of renal tubules from worms to humans. Distinctive tip cell exploratory behavior, adhesion, and basement membrane clearing underlie target recognition and dynamic interactions. Defects in these features obliterate tip cell anchorage, producing misshapen and misplaced tubules with impaired physiological function. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  18. 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

  19. Uremia causes premature ageing of the T cell compartment in end-stage renal disease patients

    Directory of Open Access Journals (Sweden)

    Meijers Ruud WJ

    2012-09-01

    Full Text Available Abstract Background End-stage renal disease (ESRD patients treated with renal replacement therapy (RRT have premature immunologically aged T cells which may underlie uremia-associated immune dysfunction. The aim of this study was to investigate whether uremia was able to induce premature ageing of the T cell compartment. For this purpose, we examined the degree of premature immunological T cell ageing by examining the T cell differentiation status, thymic output via T cell receptor excision circle (TREC content and proliferative history via relative telomere length in ESRD patients not on RRT. Results Compared to healthy controls, these patients already had a lower TREC content and an increased T cell differentiation accompanied by shorter telomeres. RRT was able to enhance CD8+ T cell differentiation and to reduce CD8+ T cell telomere length in young dialysis patients. An increased differentiation status of memory CD4+ T cells was also noted in young dialysis patients. Conclusion Based on these results we can conclude that uremia already causes premature immunological ageing of the T cell system and RRT further increases immunological ageing of the CD8+ T cell compartment in particular in young ESRD patients.

  20. 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.

  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. Metastatic renal cell carcinoma from a native kidney of a renal transplant patient diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy

    Directory of Open Access Journals (Sweden)

    Yaseen Alastal

    2015-04-01

    Full Text Available Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA biopsy sampling of enlarged lymph nodes is increasingly used to diagnose metastatic tumors, especially of the gastrointestinal tract and the lungs. Herein, we describe the diagnosis of metastatic renal cell carcinoma from a native kidney of a 54 year-old male patient, who had a 5-years history of renal transplant, by EUS-FNA of mediastinal and celiac lymph nodes. Histological and immunohistochemical findings confirmed the origin of metastatic tumor. EUS-FNA with proper cytological evaluation can be useful in the diagnosis of metastatic renal cell carcinoma in renal transplant patients. 

  3. Ex vivo hyperpolarized MR spectroscopy on isolated renal tubular cells: A novel technique for cell energy phenotyping.

    Science.gov (United States)

    Juul, Troels; Palm, Fredrik; Nielsen, Per Mose; Bertelsen, Lotte Bonde; Laustsen, Christoffer

    2017-08-01

    It has been demonstrated that hyperpolarized 13 C MR is a useful tool to study cultured cells. However, cells in culture can alter phenotype, which raises concerns regarding the in vivo significance of such findings. Here we investigate if metabolic phenotyping using hyperpolarized 13 C MR is suitable for cells isolated from kidney tissue, without prior cell culture. Isolation of tubular cells from freshly excised kidney tissue and treatment with either ouabain or antimycin A was investigated with hyperpolarized MR spectroscopy on a 9.4 Tesla preclinical imaging system. Isolation of tubular cells from less than 2 g of kidney tissue generally resulted in more than 10 million live tubular cells. This amount of cells was enough to yield robust signals from the conversion of 13 C-pyruvate to lactate, bicarbonate and alanine, demonstrating that metabolic flux by means of both anaerobic and aerobic pathways can be quantified using this technique. Ex vivo metabolic phenotyping using hyperpolarized 13 C MR in a preclinical system is a useful technique to study energy metabolism in freshly isolated renal tubular cells. This technique has the potential to advance our understanding of both normal cell physiology as well as pathological processes contributing to kidney disease. Magn Reson Med 78:457-461, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Masaki, E-mail: masakiwestriver@gmail.com [Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA (United States); University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 (United States); Yanagawa, Naomi [Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA (United States); University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 (United States); Kojima, Nobuhiko [Institute of Industrial Science (IIS), University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto [Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA (United States); University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 91343 (United States)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer We induced renal lineages from mESCs by following the in vivo developmental cues. Black-Right-Pointing-Pointer We induced nephrogenic intermediate mesoderm by stepwise addition of factors. Black-Right-Pointing-Pointer We induced two types of renal progenitor cells by reciprocal conditioned media. Black-Right-Pointing-Pointer We propose the potential role of CD24 for the enrichment of renal lineage cells. -- Abstract: The in vitro derivation of renal lineage progenitor cells is essential for renal cell therapy and regeneration. Despite extensive studies in the past, a protocol for renal lineage induction from embryonic stem cells remains unestablished. In this study, we aimed to induce renal lineages from mouse embryonic stem cells (mESC) by following in vivo developmental stages, i.e., the induction of mesoderm (Stage I), intermediate mesoderm (Stage II) and renal lineages (Stage III). For stage I induction, in accordance with known signaling pathways involved in mesoderm development in vivo, i.e., Nodal, bone morphogenic proteins (BMPs) and Wnt, we found that the sequential addition of three factors, i.e., Activin-A (A), a surrogate for Nodal signaling, during days 0-2, A plus BMP-4 (4) during days 2-4, and A4 plus lithium (L), a surrogate for Wnt signaling, during days 4-6, was most effective to induce the mesodermal marker, Brachyury. For stage II induction, the addition of retinoic acid (R) in the continuous presence of A4L during days 6-8 was most effective to induce nephrogenic intermediate mesodermal markers, such as Pax2 and Lim1. Under this condition, more than 30% of cells were stained positive for Pax2, and there was a concomitant decrease in the expression of non-mesodermal markers. For stage III induction, in resemblance to the reciprocal induction between ureteric bud (UB) and metanephric mesenchyme (MM) during kidney development, we found that the exposure to conditioned media derived from UB and MM cells was

  5. 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.)

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Report of a Rare Case of Papillary Thyroid Carcinoma Associated with Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sh. Borzouei

    2012-10-01

    Full Text Available Introduction: Papillary thyroid cancer (PTC is the most common well-differentiated cancer of the thyroid. Only in few cases of PTC entity of renal cell carcinoma has been observed in patients affected with PTC. Case Report: In this study we report a case of sporadic PTC and renal cell carcinoma in a 63 year-old woman. Conclusion: After surgery the patient was hospitalized for 1 month in ICU section. 3 months after being discharged from the hospital, she was still in a good condition and is under the follow-up treatment.(Sci J Hamadan Univ Med Sci 2012; 19 (3:75-77

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Granulated peripolar epithelial cells in the renal corpuscle of marine elasmobranch fish.

    Science.gov (United States)

    Lacy, E R; Reale, E

    1989-07-01

    Granulated epithelial cells at the vascular pole of the renal corpuscle, peripolar cells, have been found in the kidneys of five species of elasmobranchs, the little skate (Raja erinacea), the smooth dogfish shark (Mustelus canis), the Atlantic sharpnose shark (Rhizoprionodon terraenovae), the scalloped hammerhead shark (Sphyrna lewini), and the cow-nosed ray (Rhinoptera bonasus). In a sixth elasmobranch, the spiny dogfish shark (Squalus acanthias), the peripolar cells could not be identified among numerous other granulated epithelial cells. The peripolar cells are located at the transition between the parietal epithelium of Bowman's capsule and the visceral epithelium (podocytes) of the glomerulus, thus forming a cuff-like arrangement surrounding the hilar vessels of the renal corpuscle. These cells may have granules and/or vacuoles. Electron microscopy shows that the granules are membrane-bounded, and contain either a homogeneous material or a paracrystalline structure with a repeating period of about 18 nm. The vacuoles are electron lucent or may contain remnants of a granule. These epithelial cells lie close to the granulated cells of the glomerular afferent arteriole. They correspond to the granular peripolar cells of the mammalian, avian and amphibian kidney. The present study is the first reported occurrence of peripolar cells in a marine organism or in either bony or cartilagenous fish.

  12. SETD2 and PBRM1 inactivation in the development of clear cell renal cell carcinoma

    NARCIS (Netherlands)

    Li, Jun

    2016-01-01

    Kidney cancer of the clear cell type is often lethal and causes more than 100,000 deaths worldwide every year. Understanding the biology of this cancer type may help to develop better ways to diagnose and treat it. Damage in DNA (genes) is present in all cancer cells and clear cell kidney cancer is

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Protective effects of Zhibai Dihuang Wan on renal tubular cells affected with gentamicin-induced apoptosis.

    Science.gov (United States)

    Hsu, Yung-Ho; Chen, Tso-Hsiao; Wu, Mei-Yi; Lin, Yuh-Feng; Chen, Wen-Liang; Cheng, Tzu-Hurng; Chen, Cheng-Hsien

    2014-01-01

    Zhibai Dihuang Wan (ZDW) is an ancient traditional Chinese medicine composed of eight herbal ingredients and has been used to treat chronic kidney inflammation and diabetes for thousands of years. Nonetheless, the influence of ZDW on acute kidney injury is still unknown. We intended to identify the influence of ZDW on cell growth and gentamicin-induced apoptotic injury in renal tubular cells. We extracted ZDW with artificial intestinal fluid and treated rat renal tubular cells (NRK-52E) with various concentrations of the ZDW extraction. Cell proliferation and gentamicin-induced apoptosis of NRK-52E cells were evaluated using real-time proliferation monitoring and annexin V staining, respectively. Western blotting was used to evaluate the levels of Bcl-2 and caspase-3 expression. The effect of ZDW on gentamicin-induced kidney injury was also monitored in mice using the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) assay, and the measurement of serum creatinine and blood urea nitrogen. We found that 30 μg/ml of ZDW promoted cell proliferation of the rat renal tubular cells. ZDW also expressed a dose-dependent protective effect against gentamicin-induced apoptosis in the cells. Pretreatment with 3 μg/ml or 30 μg/ml of ZDW maximally increased Bcl-2 and decreased cleaved caspase-3 in the gentamicin-treated NRK-52E cells. Among the herbal ingredients of ZDW, only Phellodendron amurense Rupr., bark (Cortex Phellodendri), and Anemarrhena asphodeloides Bunge, rhizome inhibited both the gentamicin-induced Bcl-2 decrease and cleaved caspase-3 increase. Phellodendron amurense Rupr., bark and Anemarrhena asphodeloides Bunge, rhizome also inhibited gentamicin-induced apoptosis at particular concentrations; however, these two ingredients were less effective than ZDW. In the mouse model of gentamicin-induced nephropathy, the ZDW treatment significantly reduced apoptotic cells in the renal cortex and improved renal function. Our

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

    Energy Technology Data Exchange (ETDEWEB)

    Mellas, J.; Hammerman, M.R.

    1986-03-01

    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/sup +/-H/sup +/ 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 (/sup 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 ..gamma.. phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular (Na/sup +/) > intracellular (Na/sup +/), was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na/sup +/-H/sup +/ 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.

  19. DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

    Science.gov (United States)

    Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

    2014-07-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Sodium butyrate induces cell death by autophagy and reactivates a tumor suppressor gene DIRAS1 in renal cell carcinoma cell line UOK146.

    Science.gov (United States)

    Verma, Shiv Prakash; Agarwal, Ayushi; Das, Parimal

    2018-04-01

    Sodium butyrate (SB), a histone deacetylase inhibitor, is emerging as a potent anti-cancer drug for different types of cancers. In the present study, anti-cancer activity of SB in Xp11.2 (TFE3) translocated renal cell carcinoma cell line UOK146 was studied. Anti-proliferative effect of SB in renal cell carcinoma (RCC) cell line UOK146 was evaluated by MTT assay and morphological characteristics were observed by phase contrast microscopy which displayed the cell death after SB treatment. SB induces DNA fragmentation and change in nuclear morphology observed by increased sub-G1 region cell population and nuclear blebbings. Cell cycle arrest at G2/M phase was found after SB treatment. UOK146 cell line shows autophagy mode of cell death as displayed by acridine orange staining and flow cytometry analysis. LC3-II, a protein marker of autophagy, was also found to be upregulated after SB treatment. A tumor suppressor gene DIRAS1 was upregulated after SB treatment, displaying its anti-cancer potential at molecular level. These findings suggest that SB could serve as a novel regulator of tumor suppressors and lead to the discovery of novel therapeutics with better and enhanced anti-cancer activity.

  1. Regulation of renin secretion by renal juxtaglomerular cells

    DEFF Research Database (Denmark)

    Friis, Ulla G; Madsen, Kirsten; Stubbe, Jane

    2013-01-01

    inhibits renin secretion likely through attenuated formation and enhanced degradation of cAMP; by activation of chloride currents and interaction with calcineurin. Connexin 40 is necessary for localization of JG cells in the vascular wall and for pressure- and macula densa-dependent suppression of renin...

  2. 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

  3. Endothelial protein C receptor in renal tubular epithelial cells and ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... nuclear factor-kappa B (NF-KB). This will result in the inhibition of the expression of cell surface adhesion molecules and the reduction in the synthesis and release of inflammatory cytokine, inhibiting neutrophil activation and extravasation in damaged tissue parts. Endothelial protein C receptor (EPCR) was ...

  4. The expression of aquaporin 1 in renal cell carcinomal before and after interventional treatment and its significance

    International Nuclear Information System (INIS)

    Wu Jingtao; Guo Yan; Zhao Yongsheng; Yang Haishan; Wang Tianwei; Wang Baoming

    2006-01-01

    Objective: To evaluate the effect of interventional treatment on the expression level and distribution of aquaporin 1 (AQP1) in renal cell carcinoma and its significance. Methods: Fifteen cases of renal cell carcinoma tissues which received chemotherapy embolism before nephrectomy and 12 cases of renal cell carcinoma tissues which only had nephrectomy were studied as test group. Twelve cases of normal kidney tissues were studied as control groups. RT-PCR, western blot analysis and immunohistochemical method were performed to detect the expression of AQP1 on different tissues. Results: In normal kidney tissues, AQP1 expressed in the capillary endothelia cells of glomerulus, epithelial cell of proximal tubules. In renal cell carcinoma tissues, AQP1 expressed in tumor cells and epithelial cells of capillary vessel. Expression of AQP1 remarkably decreased in renal cell carcinoma tissues compared with normal kidney tissues (Pixel intensity rate of AQP1 and β-actin by RT-PCR methods were 0.935 and 0.855 respectively; AQP1 positive pixel intensity by western blot methods were 125.8 and 147.4 respectively; positive index of AQP1 pixel intensity by immunohistochemical method were 1.31 and 1.08, P<0.01). Expression of AQP1 remarkably decreased in renal cell carcinoma tissues which received chemotherapy embolism compared with renal cell carcinoma which only had nephrectomy (Pixel intensity rate of AQP1 and β-actin by RT-PCR methods was 0.810; AQP1 positive pixel intensity by western blot methods was 159.7; positive index of AQP1 pixel intensity by immunohistochemical method was 0.82, P<0.05). Conclusion: Interventional treatment can depress the expression of AQP1 in renal cell carcinoma and suppress the growth and metastasis of renal cell carcinoma. (authors)

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

    Science.gov (United States)

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

    2004-11-01

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

  6. The cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules.

    Science.gov (United States)

    Halberg, Kenneth A; Rainey, Stephanie M; Veland, Iben R; Neuert, Helen; Dornan, Anthony J; Klämbt, Christian; Davies, Shireen-Anne; Dow, Julian A T

    2016-04-13

    Multicellular organisms rely on cell adhesion molecules to coordinate cell-cell interactions, and to provide navigational cues during tissue formation. In Drosophila, Fasciclin 2 (Fas2) has been intensively studied due to its role in nervous system development and maintenance; yet, Fas2 is most abundantly expressed in the adult renal (Malpighian) tubule rather than in neuronal tissues. The role Fas2 serves in this epithelium is unknown. Here we show that Fas2 is essential to brush border maintenance in renal tubules of Drosophila. Fas2 is dynamically expressed during tubule morphogenesis, localizing to the brush border whenever the tissue is transport competent. Genetic manipulations of Fas2 expression levels impact on both microvilli length and organization, which in turn dramatically affect stimulated rates of fluid secretion by the tissue. Consequently, we demonstrate a radically different role for this well-known cell adhesion molecule, and propose that Fas2-mediated intermicrovillar homophilic adhesion complexes help stabilize the brush border.

  7. Outcome of papillary versus clear cell renal cell carcinoma varies significantly in non-metastatic disease.

    Directory of Open Access Journals (Sweden)

    Nina Wagener

    Full Text Available Renal cell carcinoma (RCC comprises a heterogenous group of tumors. Traditionally, papillary RCC (pRCC is associated with a favorable outcome compared to clear cell RCC (ccRCC, while other series report equivalent or worse prognosis. In this paper we comparatively evaluate outcome of pRCC versus ccRCC in two large multi-institutional databases (cohort study, including distribution of pRCC subtypes 1 and 2. Retrospective data of 1,943 surgically treated pRCC patients from 17 European/ North American centers between 1984-2015 were compared to 5,600 ccRCC patients from a database comprising 11 European/ North American centers (1984-2011. Median follow-up was 64.6 months. Differences between pRCC, subtypes, and ccRCC were compared with t-tests, Chi^2-tests, and exact Fisher tests. Cancer-specific mortality was analyzed with cumulative incidence curves and Cox cause-specific hazard models. The robustness of our results was examined with sensitivity analyses. We present that cancer-specific mortality rates and variables as stage, lymph node, and distant metastasis differ significantly between groups. Furthermore, we demonstrate that patients with non-metastatic pRCC had a significantly better cancer-specific mortality (HR 0.76, p = 0.007, when compared to ccRCC. Additionally, pRCC type 2 versus ccRCC exhibited no difference in cancer-specific mortality (HR 0.9, p = 0.722, whereas pRCC type 1 versus ccRCC displayed a risk of death reduced by 69% (p = 0.044. Taken together, outcome of pRCC versus ccRCC varies significantly in non-metastatic disease. Furthermore, pRCC type 2 exhibited no difference in cancer-specific mortality, whereas pRCC type 1 displayed a significantly reduced risk of death. Consequently, there is urgent need to respect histopathological entities and their subtypes, when assigning follow-up or targeted therapy to RCC patients.

  8. Relevance and therapeutic possibility of PTEN-long in renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog. Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt. Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance.

  9. Upregulation of nestin in proximal tubules may participate in cell migration during renal repair.

    Science.gov (United States)

    Wen, Donghai; Ni, Li; You, Li; Zhang, Liying; Gu, Yong; Hao, Chuan-Ming; Chen, Jing

    2012-12-01

    The characteristics of renal tubular progenitor/precursor cells and the role of renal tubule regeneration in the repair of remnant kidneys (RKs) after nephrectomy are not well known. In the present study of a murine model of subtotal nephrectomy, we used immunofluorescence (IF), immunoblot analysis, and in situ hybridization methods to demonstrate that nestin expression was transiently upregulated in tubule cells near the incision edges of RKs. The nestin-positive tubules were immature proximal tubules that colabeled with lotus tetragonolobus agglutinin but not with markers of mature tubules (aquaporin-1, Tamm-Horsfall protein, and aquaporin-2). In addition, many of the nestin-expressing tubule cells were actively proliferative cells, as indicated by colabeling with bromodeoxyuridine. Double-label IF and immunoblot analysis also showed that the upregulation of tubular nestin was associated with enhanced transforming growth factor-β1 (TGF-β1) expression in the incision edge of RKs but not α-smooth muscle actin, which is a marker of fibrosis. In cultured human kidney proximal tubule cells (HKC), immunoblot analysis indicated that TGF-β1 induced nestin expression and loss of E-cadherin expression, suggesting an association of nestin expression and cellular dedifferentiation. Knockdown of nestin expression by a short hairpin RNA-containing plasmid led to decreased migration of HKC cells that were induced by TGF-β1. Taken together, our results suggest that the tubule repair that occurs during the recovery process following nephrectomy may involve TGF-β1-induced nestin expression in immature renal proximal tubule cells and the promotion of renal cell migration.

  10. Bilateral renal cell carcinoma with leiomyomatous stroma: A rare entity diagnosed synchronously and treated surgically in a staged fashion.

    Science.gov (United States)

    Kiremit, Murat Can; Acar, Ömer; Sağlıcan, Yeşim; Esen, Tarık

    2017-12-01

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90-95% of kidney neoplasms. Renal cell carcinoma with leiomyomatous stroma (RCCLS) is an extremely rare histopathological entity based on available literature data. Herein, we report a 31-year-old male with incidentally detected synchronous bilateral renal masses who was eventually found to harbor RCCLS after being operated sequentially via nephron-sparing surgery.

  11. 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.

  12. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

    Science.gov (United States)

    Livingston, Man J.; Ding, Han-Fei; Huang, Shuang; Hill, Joseph A.; Yin, Xiao-Ming; Dong, Zheng

    2016-01-01

    ABSTRACT Renal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUO-associated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/α-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils. Tubular atrophy, apoptosis, nephron loss, and interstitial macrophage infiltration were all inhibited in these mice. Moreover, these mice showed a specific suppression of the expression of a profibrotic factor FGF2 (fibroblast growth factor 2). In vitro, TGFB1 (transforming growth factor β 1) induced autophagy, apoptosis, and FN1 accumulation in primary proximal tubular cells. Inhibition of autophagy suppressed FN1 accumulation and apoptosis, while enhancement of autophagy increased TGFB1-induced-cell death. These results suggest that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO. The profibrotic function of autophagy is related to the regulation on tubular cell death, interstitial inflammation, and the production of profibrotic factors. PMID:27123926

  13. Higher HLA class I expression in renal cell carcinoma than in autologous normal tissue.

    Science.gov (United States)

    Sáenz-López, P; Gouttefangeas, C; Hennenlotter, J; Concha, A; Maleno, I; Ruiz-Cabello, F; Cózar, J M; Tallada, M; Stenzl, A; Rammensee, H-G; Garrido, F; Cabrera, T

    2010-02-01

    A total of 93 frozen primary renal cell carcinoma (RCC) samples and 31 frozen samples of corresponding normal renal tissue were analyzed for human leukocyte antigen (HLA) class I and HLA-DR expression. Unexpectedly, HLA class I expression was much higher on RCC cells than on normal renal tubular cells. Immunohistochemistry analysis of frozen and paraffin-embedded tissue samples, applying an extended panel of specific anti-HLA monoclonal antibodies, showed elevated HLA class I antigen expression in 95.6% of the tumors vs only 12.9% of normal renal tissues. These findings were confirmed by molecular analysis of HLA heavy chain and beta2-microglobulin (beta2m) transcription levels using quantitative real-time polymerase chain reaction (PCR) on microdissected tissue samples (isolated tumor nests and autologous normal renal tubules) from four patients. These results might help to explain the relatively high success rate of immunotherapy in patients with RCC. The molecular mechanism underlying the increased HLA class I expression in RCC has yet to be elucidated.

  14. 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.

  15. Renal papillary necrosis in patients with sickle cell disease: How to recognize this 'forgotten' diagnosis.

    Science.gov (United States)

    Henderickx, Michaël M E L; Brits, Tim; De Baets, Karen; Seghers, Mattias; Maes, Philip; Trouet, Dominique; De Wachter, Stefan; De Win, Gunter

    2017-06-01

    Renal papillary necrosis is not commonly seen in daily practice, but can have severe consequences when it is not diagnosed in time. It is known to be associated with sickle cell hemoglobinopathies; however a wide range of etiologies are possible, and it is therefore not the first diagnosis clinicians consider in patients with sickle cell disease who present with hematuria. A literature search was performed to summarize the current knowledge about renal papillary necrosis associated with sickle cell disease. These findings are illustrated with a case of a 9-year old girl with sickle cell disease who was referred with painless gross hematuria. Typical radiologic signs for renal papillary necrosis are necrotic cavities that fill with contrast, small collections of contrast peripheral to the calyces in the papillary region (ball-on-tee sign), calcification of the papillary defect, filling defects, hydronephrosis, blunted papillary tip, clefts in the renal medulla filled with contrast, hyperattenuated medullary calcifications, non-enhanced lesions surrounded by rings of excreted contrast, and clubbed calyces. This study focuses on the pathophysiology of renal papillary necrosis associated with sickle cell disease, the possible symptoms, as well as the diagnostic steps, with a special interest in particular presentation on old (retrograde pyelography) and new (computed tomography) gold standard in radiologic imaging, and the management for this pathology. This study aims to remind clinicians of this "forgotten" diagnosis and what signs to look for in pediatric patients with sickle cell disease who present with hematuria. In pediatric cases radiation protection is important, therefore knowing what radiologic signs can be found on retrograde pyelography can lead to early identification of this pathology without having to proceed to computed tomography. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  16. Tissue and Metabolomic Biomarkers of Recurrent Renal Cell Carcinoma

    Science.gov (United States)

    2014-07-01

    glycosphingolipid metabolism is dysfunctional in lupus mice and patients with nephritis . J. Am. Soc. Nephrol., In press. 5. Jones, E.E., Dworski, S., Canals, D...course for the most common clear cell form (ccRCC). The primary treatment for patients with localized ccRCC is surgical excision, which can be highly...accurately predicting which patients will experience metastatic progression following surgery for localized ccRCC and 2) develop new treatments

  17. Vegetable and fruit consumption and risk of renal cell carcinoma: results from the Netherlands cohort study.

    NARCIS (Netherlands)

    Dijk, B.A. van; Schouten, L.J.; Kiemeney, L.A.L.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2005-01-01

    Vegetable and fruit consumption is generally inversely associated with various cancer types, including renal cell carcinoma (RCC). The Netherlands cohort study on diet and cancer (NLCS) consists of 120,852 men and women, aged 55-69 years, who filled out a self-administered questionnaire that

  18. Vegetable and fruit consumption and risk of renal cell carcinoma: Results from the Netherlands cohort study

    NARCIS (Netherlands)

    Dijk, B.A.C. van; Schouten, L.J.; Kiemeney, L.A.L.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2005-01-01

    Vegetable and fruit consumption is generally inversely associated with various cancer types, including renal cell carcinoma (RCC). The Netherlands cohort study on diet and cancer (NLCS) consists of 120,852 men and women, aged 55-69 years, who filled out a self-administered questionnaire that

  19. 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

  20. 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...

  1. 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 ...

  2. Chromophobe renal cell carcinoma in an 18-year-old female

    African Journals Online (AJOL)

    I. Saguem

    2016-08-01

    Aug 1, 2016 ... Abstract. Renal cell carcinoma (RCC) in young adults is uncommon. Whether they have different clinicopathologic characteristics and outcomes from those in older patients is still a conflicting matter. In this article we present an uncommon subtype of RCC which is chromophobe RCC (chRCC) in a female ...

  3. Renal function influences interleukin-8 background production by cultured human mesothelial cells

    NARCIS (Netherlands)

    Visser, C. E.; Brouwer-Steenbergen, J. J.; Postmus, P. E.; Meijer, S.; Struijk, D. G.; Krediet, R. T.; Beelen, R. H.

    1996-01-01

    Previous studies have demonstrated that mesothelial cells (MC) are important in the local host defense system of the peritoneal cavity. Most studies on the function of MC are performed on MC derived from material of patients with normal renal function (NRF). The aim of the present study was to

  4. 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...

  5. 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, ...

  6. The role of HUCB derived stem cells therapy in repair of renal ...

    African Journals Online (AJOL)

    Acute renal failure (ARF) is a common clinical problem with increasing incidence, serious consequences, unsatisfactory therapeutic options and enormous financial burden to society. The aim is to investigate the role of human umbilical cord blood (HUCB) derived mesenchymal (MSCs) and CD34+ hematopoietic stem cell ...

  7. 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...

  8. Metastatic Renal Cell Carcinoma to the Thyroid 23 Years After Nephrectomy

    Directory of Open Access Journals (Sweden)

    Carrie Valdez

    2014-07-01

    Full Text Available Thyroid carcinoma is an uncommon form of human cancer, with an outstanding overall cure rate. This excellent prognosis is based on the fact that well over 99% of thyroid cancers are primary tumors. Metastatic cancer to the thyroid remains very rare. We report a case of clear cell renal carcinoma metastatic to the thyroid gland 23 years after nephrectomy.

  9. Metastatic Renal Cell Carcinoma to the Thyroid 23 Years After Nephrectomy ?

    OpenAIRE

    Valdez, Carrie; Rezaei, M. Katayoon; Hendricks, Fredrick; Knoll, Stanley M.

    2014-01-01

    Thyroid carcinoma is an uncommon form of human cancer, with an outstanding overall cure rate. This excellent prognosis is based on the fact that well over 99% of thyroid cancers are primary tumors. Metastatic cancer to the thyroid remains very rare. We report a case of clear cell renal carcinoma metastatic to the thyroid gland 23 years after nephrectomy.

  10. 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

  11. EORTC-GU group expert opinion on metastatic renal cell cancer

    NARCIS (Netherlands)

    de Reijke, Theo M.; Bellmunt, Joaquim; van Poppel, Hein; Marreaud, Sandrine; Aapro, Matti

    2009-01-01

    There is no consensus on the detailed surveillance of renal cell cancer (RCC) patients after radical resection of the kidney. Where relapse is unlikely, one reasonable option would be to confine investigations to chest X-ray and abdominal ultrasound-carried out at 3-month intervals during the first

  12. Radioactive seed localization of renal cell carcinoma in a patient with Von Hippel-Lindau disease

    DEFF Research Database (Denmark)

    Hassing, Christina Marie Schiottz; Tvedskov, Tove Filtenborg; Kroman, Niels

    2017-01-01

    This report describes the case of a patient, who had successful radioactive seed localization (RSL) performed to improve the identification and excision of a renal cell carcinoma. RSL is a new method of preoperative localization, which can ease the surgical procedure, minimize tissue trauma...

  13. 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 patie...

  14. Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2

    DEFF Research Database (Denmark)

    Geertsen, P F; Hermann, G G; von der Maase, H

    1992-01-01

    PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2...

  15. Primary Thyroid-Like Follicular Renal Cell Carcinoma: An Emerging Entity

    Directory of Open Access Journals (Sweden)

    S. Malde

    2013-01-01

    Full Text Available Primary thyroid-like follicular carcinoma of the kidney is a rare but newly emerging histological variant of renal cell carcinoma RCC, with only nine cases reported in the literature to date. We present a further case of this unique condition, discuss the workup and typical histological findings, and review the literature regarding this rare histological variant.

  16. 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

  17. Metastatic renal cell carcinoma mimicking diverticulitis in a patient with chronic lymphocytic leukaemia.

    Science.gov (United States)

    Hwang, S M; Kuyava, J M; Grande, J P; Swetz, K M

    2015-01-07

    We present an unusual case of metastatic renal cell carcinoma (RCC) mimicking diverticulitis in a 76-year-old man with a 16-year history of chronic lymphocytic leukaemia (CLL) and a 2 cm left renal mass. The patient presented with severe abdominal pain and lower gastrointestinal bleeding with anticoagulation from recent pulmonary embolism. His clinical course was troubled by recurrent hospitalisations and complications that delayed investigations and potential treatments. Radiographic findings revealed stable CLL, mild sigmoid diverticulitis and a small renal mass. Small renal masses (less than 4 cm) are considered low risk for metastasising and are, thus, often observed or ablated, rather than resected. Furthermore, gastrointestinal metastases from RCC are rare. This case adds new perspective to the unpredictable nature of RCC and how synchronous malignancies may be masked in patients with long-standing CLL. 2015 BMJ Publishing Group Ltd.

  18. CT staging of renal cell carcinoma: Emphasis on perinephric tumor extension

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Young; Kim, Sun Mi; Choi, Mun Hwan; Bang, Duk Ja; Koh, Byung Hee; Cho, On Koo [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1993-07-15

    A total of 47 preoperative CT scans in patients with renal cell carcinoma were retrospectively reviewed and compared with surgical findings to assess the accuracy of CT for determining the perinephric tumor extension. CT criteria for perinephric extension were hazy ill-defined tumor margin, perirenal nodule and fascial thickening. Regardless of the tumor stage, the accuracy of CT in detecting perinephric extension was 76.6% (36/47), with a sensitivity of 88.9% (16/18) and specificity of 68.9% (20/29). The cause of understaging (n=2) was microscopic infiltration of the perinephric space. The causes of overstaging were tumor infiltration to the renal capsule (n=5), partial adhesion with the perinephric fat (n=3) and renal vein thrombosis (n=1). A smooth clear tumor margin is highly reliable sign for stage I but infiltrative findings onto renal capsule and perirenal fat could be considered stage I.

  19. Renal vein stenting abates sickle cell trait mediated chronic refractory hematuria exacerbated by the Nutcracker phenomenon

    Directory of Open Access Journals (Sweden)

    Naiem Nassiri

    2017-11-01

    Full Text Available Nutcracker syndrome (NCS is a rare vascular anomaly involving left renal vein (LRV outflow entrapment most commonly between the aorta and the superiormesenteric artery (SMA. This can lead to chronic LRV hypertension with resultant gonadal vein reflux, pelvic varicosity formation, hematuria, anemia, failure to thrive, and if severe enough, renal failure. Sickle cell trait (SCT is a well-known and relatively common cause of hematuria causing damage to the renal microvasculature with subsequent renal papillary necrosis. In the rare setting of both conditions, LRV compression exacerbates upstream LRV sickling and exponentially augments hematuria. As is presented here, alleviation of LRV compression via a minimally endovascular approach can cease life-threatening hematuria.

  20. Renal Operational Tolerance Is Associated With a Defect of Blood Tfh Cells That Exhibit Impaired B Cell Help.

    Science.gov (United States)

    Chenouard, A; Chesneau, M; Bui Nguyen, L; Le Bot, S; Cadoux, M; Dugast, E; Paul, C; Malard-Castagnet, S; Ville, S; Guérif, P; Soulillou, J-P; Degauque, N; Danger, R; Giral, M; Brouard, S

    2017-06-01

    Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper (Tfh) cells play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh cells from TOL displayed a modified gene expression profile, failed to produce interleukin-21, and were unable to induce IgG production by naive B cells. This Tfh defect is linked to a low incidence of postgraft de novo donor-specific antibody (dnDSA) immunization, suggesting that the lack of Tfh cells in TOL may induce a protolerogenic environment with reduced risk of developing dnDSA. Finally, we showed that elevated Tfh in STA precedes the occurrence of dnDSA during an alloresponse. These data provide new insights into the mechanisms of antibody response in operational tolerance. Disrupted homeostasis and impaired Tfh function in TOL could lead to a reduced risk of developing dnDSA and suggest a predictive role of blood Tfh cells on the occurrence of dnDSA in transplant recipients. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    Directory of Open Access Journals (Sweden)

    Francis A. Ennis

    2011-07-01

    Full Text Available 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 responses negatively correlated with disease severity, but in another report the number of regulatory T cells, which are thought to suppress T cell responses, negatively correlated with disease severity. In rat experiments, in which hantavirus causes persistent infection, depletion of regulatory T cells helped infected rats clear virus without inducing immunopathology. These seemingly contradictory findings may suggest delicate balance in T cell responses between protection and immunopathogenesis. Both too strong and too weak T cell responses may lead to severe disease. It is important to clarify the role of T cells in these diseases for better treatment (whether to suppress T cell functions and protection (vaccine design which may need to take into account viral factors and the influence of HLA on T cell responses.

  2. 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)

  3. Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Weber T

    2014-05-01

    Full Text Available Thomas Weber,1,2 Matthias Meinhardt,3 Stefan Zastrow,1 Andreas Wienke,4 Kati Erdmann,1 Jörg Hofmann,1 Susanne Fuessel,1 Manfred P Wirth11Department of Urology, Technische Universität Dresden, Dresden, Germany; 2Department of Oncology and Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale, Germany; 3Institute of Pathology, Technische Universität Dresden, Dresden, Germany; 4Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale, GermanyPurpose: To enhance prognostic information of protein biomarkers for clear cell renal cell carcinomas (ccRCCs, we analyzed them within prognostic groups of ccRCC harboring different tumor characteristics of this clinically and molecularly heterogeneous tumor entity.Methods: Tissue microarrays from 145 patients with primary ccRCC were immunohistochemically analyzed for VHL (von Hippel-Lindau tumor suppressor, Ki67 (marker of proliferation 1, p53 (tumor protein p53, p21 (cyclin-dependent kinase inhibitor 1A, survivin (baculoviral IAP repeat containing 5, and UEA-1 (ulex europaeus agglutinin I to assess microvessel-density.Results: When analyzing all patients, nuclear staining of Ki67 (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04–1.12 and nuclear survivin (nS; HR 1.04, 95% CI 1.01–1.08 were significantly associated with disease-specific survival (DSS. In the cohort of patients with advanced localized or metastasized ccRCC, high staining of Ki67, p53 and nS predicted shorter DSS (Ki67: HR 1.07, 95% CI 1.02–1.11; p53: HR 1.05, 95% CI 1.01–1.09; nS: HR 1.08, 95% CI 1.02–1.14. In organ-confined ccRCC, patients with high p21-staining had a longer DSS (HR 0.96, 95% CI 0.92–0.99. In a multivariate model with stepwise backward elimination, tumor size and p21-staining showed a significant association with DSS in patients with "organ-confined" ccRCCs. The p21-staining increased the concordance index of tumor size from

  4. 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.

  5. Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

    International Nuclear Information System (INIS)

    Twite, Nicolas; Andrei, Graciela; Kummert, Caroline; Donner, Catherine; Perez-Morga, David; De Vos, Rita; Snoeck, Robert; Marchant, Arnaud

    2014-01-01

    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. Distinct mesenchymal alterations in N-cadherin and E-cadherin positive primary renal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Christof Keller

    Full Text Available Renal tubular epithelial cells of proximal and distal origin differ markedly in their physiological functions. Therefore, we hypothesized that they also differ in their capacity to undergo epithelial to mesenchymal alterations.We used cultures of freshly isolated primary human tubular cells. To distinguish cells of different tubular origin we took advantage of the fact that human proximal epithelial cells uniquely express N-cadherin instead of E-cadherin as major cell-cell adhesion molecule. To provoke mesenchymal alteration we treated these cocultures with TGF-β for up to 6 days. Within this time period, the morphology of distal tubular cells was barely altered. In contrast to tubular cell lines, E-cadherin was not down-regulated by TGF-β, even though TGF-β signal transduction was initiated as demonstrated by nuclear localization of Smad2/3. Analysis of transcription factors and miRNAs possibly involved in E-cadherin regulation revealed high levels of miRNAs of the miR200-family, which may contribute to the stability of E-cadherin expression in human distal tubular epithelial cells. By contrast, proximal tubular epithelial cells altered their phenotype when treated with TGF-β. They became elongated and formed three-dimensional structures. Rho-kinases were identified as modulators of TGF-β-induced morphological alterations. Non-specific inhibition of Rho-kinases resulted in stabilization of the epithelial phenotype, while partial effects were observed upon downregulation of Rho-kinase isoforms ROCK1 and ROCK2. The distinct reactivity of proximal and distal cells was retained when the cells were cultured as polarized cells.Interference with Rho-kinase signaling provides a target to counteract TGF-β-mediated mesenchymal alterations of epithelial cells, particularly in proximal tubular epithelial cells. Furthermore, primary distal tubular cells differed from cell lines by their high phenotypic stability which included constant expression of E

  7. Renal cell carcinoma: Physician - related delayed in diagnosis

    International Nuclear Information System (INIS)

    Parvez, T.

    2000-01-01

    Physician-related delay in treatment is a very serious issue and clear protocols for management need to be identified. Given below is a case of a patient with solid renal mass. In spite of all relevant and repeated investigations he was not operated at proper time until his solid renal mass became locally advanced and metastatic. With the present treatment, patient has lived median survival time for this disease. The prognosis was very bad. If he had been operated at his first presentation he would have lived a normal life with even one kidney. (author)

  8. Prognostic factors and risk classifications for patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Shinohara, Nobuo; Abe, Takashige

    2015-10-01

    The introduction of molecular-targeted therapy has made dramatical changes to treatment for metastatic renal cell carcinoma. Currently, there are four vascular endothelial growth factor receptor-tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors in Japan. For the appropriate clinical use of these molecular-targeted drugs, the identification of prognostic and/or predictive factors in patients who received these drugs is required. Although molecular biological and genetic factors that determine the prognosis of patients with metastatic renal cell carcinoma have been reported, most of these factors are problematic in that the number of patients analyzed was small. In contrast, clinicopathological prognostic factors, including the practice of cytoreductive nephrectomy, pathological findings, metastatic sites and metastasectomy, and abnormal inflammatory response, have been identified by analyzing a relatively large number of patients. Several prognostic classification models that were developed by combining these clinicopathological factors are widely used in not only clinical trials, but also routine clinical practice. However, the quality of these prognostic models is considered to be insufficient regarding prognostic prediction of metastatic renal cell carcinoma patients and, thus, requires further improvements. Recently, basic and clinical studies have been extensively carried out for the identification of promising informative markers and for understanding molecular mechanisms of resistance to molecular-targeted drugs in metastatic renal cell carcinoma patients. The present review considers ongoing translational research efforts on clinicopathological, molecular biological, and genetic prognostic and/or predictive factors for metastatic renal cell carcinoma patients in the era of molecular-targeted therapy, and discusses the clinical implications of these findings. © 2015 The Japanese Urological Association.

  9. 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

  10. Stage T3a renal cell carcinoma: staging accuracy of CT for sinus fat, perinephric fat or renal vein invasion.

    Science.gov (United States)

    Sokhi, H K; Mok, W Y; Patel, U

    2015-01-01

    To study the accuracy of CT for staging T3a (TNM 2009) renal cell carcinoma (RCC). Unenhanced and nephrographic phase CT studies of 117 patients (male:female = 82:35; age range, 21-86 years) with T1-T3a RCC were independently reviewed by 2 readers. The presence of sinus or perinephric fat, or renal vein invasion and tumour characteristics were noted. Median (range) tumour size was 5.5 (0.9-19.0) cm; and 46 (39%), 16 (14%) and 55 (47%) tumours were pT1, pT2 and pT3a RCC, respectively. The sensitivity/specificity for sinus fat, perinephric fat and renal vein invasion were 71/79%, 83/76% and 59/93% (Reader 1) and 88/71%, 68/72% and 69/91% (Reader 2) with κ = 0.41, 0.43 and 0.61, respectively. Sinus fat invasion was seen in 47/55 (85%) cases with T3a RCC vs 16/55 (29%) and 33/55 (60%) for perinephric fat and renal vein invasion. Tumour necrosis, irregularity of tumour edge and direct tumour contact with perirenal fascia or sinus fat increased the odds of local invasion [odds ratio (OR), 2.5-3.7; p fat invasion was the most common invasive feature. Centrally situated renal tumours with an irregular tumour edge, inseparable from sinus structures or the perirenal fascia and CT features of tumour necrosis should alert the reader to the possibility of Stage T3a RCC (OR, 2.5-3.9).

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

    African Journals Online (AJOL)

    Amar A. Dowd

    cancers [2]. It is a collection of different types of neoplasms, each derived from the various parts of the nephron (epithelium or renal tubules) and possessing distinct genetic characteristics, histological features, and to some extent, clinical phenotypes [9]. .... There was no evidence of colonic or gastric carci- noma or ...

  12. microRNA-184 functions as tumor suppressor in renal cell carcinoma.

    Science.gov (United States)

    Su, Zhengming; Chen, Duqun; Li, Yifan; Zhang, Enpu; Yu, Zuhu; Chen, Ting; Jiang, Zhimao; Ni, Liangchao; Yang, Shangqi; Gui, Yaoting; Ye, Jiongxian; Lai, Yongqing

    2015-03-01

    microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of approximately 22 nucleotides in length that function as post-transcriptional gene regulators. Their aberrant expression may be involved in human diseases, including cancer. Although miRNA-184 (miR-184) has been reported in other tumors, its function in renal cell carcinoma (RCC) is still unknown. The aim of the present study was to investigate the role of miR-184 in RCC. The impacts of miR-184 on cell migration, proliferation and apoptosis were evaluated using migration scratch, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assay. Our studies revealed that miR-184 mimic significantly inhibits cell migration, suppresses cell proliferation and induces renal cancer cell apoptosis in vitro when compared with the negative control (P184 played a significant role as a tumor suppressor in RCC. Therefore, miR-184 may be a promising therapeutic target for renal cancer treatment in the future.

  13. Classification of Five Uremic Solutes according to Their Effects on Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Takeo Edamatsu

    2014-01-01

    Full Text Available Background/Aims. Uremic solutes, which are known to be retained in patients with chronic kidney disease, are considered to have deleterious effects on disease progression. Among these uremic solutes, indoxyl sulfate (IS has been extensively studied, while other solutes have been studied less to state. We conducted a comparative study to examine the similarities and differences between IS, p-cresyl sulfate (PCS, phenyl sulfate (PhS, hippuric acid (HA, and indoleacetic acid (IAA. Methods. We used LLC-PK1 cells to evaluate the effects of these solutes on viable cell number, cell cycle progression, and cell death. Results. All the solutes reduced viable cell number after 48-hour incubation. N-Acetyl-L-cysteine inhibited this effect induced by all solutes except HA. At the concentration that reduced the cell number to almost 50% of vehicle control, IAA induced apoptosis but not cell cycle delay, whereas other solutes induced delay in cell cycle progression with marginal impact on apoptosis. Phosphorylation of p53 and Chk1 and expression of ATF4 and CHOP genes were detected in IS-, PCS-, and PhS-treated cells, but not in IAA-treated cells. Conclusions. Taken together, the adverse effects of PCS and PhS on renal tubular cells are similar to those of IS, while those of HA and IAA differ.

  14. 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.

  15. Severe Dyspnea due to Pulmonary Metastasis of Renal Cell Carcinoma: Is Cytoreductive Surgery of Value

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Moslemi

    2010-09-01

    Full Text Available Here, we present a case in which cytoreductive surgery, like left radical nephrectomy, was effective in the treatment of pulmonary metastases and para-aortic metastases from renal cell carcinoma. A 28-year-old man underwent left radical nephrectomy with pulmonary metastasectomy for the diagnosis of metastatic left renal cell carcinoma. The histologic diagnosis was clear cell carcinoma G2, pT3N1M1. He subsequently underwent i.m. administration of IFN-α, 5 million units per day for 30 days. The nasal oxygen mask was weaned gradually, and the chest tube was removable due to cessation of the continuous production of pleural fluid. The patient was well until one year after operation.

  16. Autoantibodies and Resident Renal Cells in the Pathogenesis of Lupus Nephritis: Getting to Know the Unknown

    Directory of Open Access Journals (Sweden)

    Susan Yung

    2012-01-01

    Full Text Available Systemic lupus erythematosus is characterized by a breakdown of self-tolerance and production of autoantibodies. Kidney involvement (i.e., lupus nephritis is both common and severe and can result in permanent damage within the glomerular, vascular, and tubulo-interstitial compartments of the kidney, leading to acute or chronic renal failure. Accumulating evidence shows that anti-dsDNA antibodies play a critical role in the pathogenesis of lupus nephritis through their binding to cell surface proteins of resident kidney cells, thereby triggering the downstream activation of signaling pathways and the release of mediators of inflammation and fibrosis. This paper describes the mechanisms through which autoantibodies interact with resident renal cells and how this interaction plays a part in disease pathogenesis that ultimately leads to structural and functional alterations in lupus nephritis.

  17. 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.

  18. 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

  19. 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

  20. Nivolumab-associated Nephrotic Syndrome in a Patient With Renal Cell Carcinoma: A Case Report.

    Science.gov (United States)

    Daanen, Robin A; Maas, Rutger J H; Koornstra, Rutger H T; Steenbergen, Eric J; van Herpen, Carla M L; Willemsen, Annelieke E C A B

    Immune checkpoint inhibitors have taken an important place in the treatment of different types of malignancies. These drugs are known to have specific immune-mediated adverse events. We describe a case of severe nephrotic syndrome secondary to treatment with nivolumab in a patient with renal cell carcinoma. A 62-year-old man was treated with nivolumab for papillary renal cell carcinoma type 2 for 8 weeks when he was admitted to the hospital with a severe nephrotic syndrome and acute kidney injury. Renal biopsy showed focal segmental glomerulosclerosis. Treatment with high-dose corticosteroids had insufficient effect, but the addition of mycophenolate mofetil resulted in remission of the nephrotic syndrome and recovery of renal function. Proteinuria subsequently relapsed during corticosteroid tapering. The time course in this patient strongly suggests that the nephrotic syndrome occurred as an adverse drug reaction to nivolumab treatment. If during nivolumab treatment renal insufficiency, hypoalbuminemia, or proteinuria develops, further analysis for a possible nephrotic syndrome is warranted for early detection and treatment of this life-threatening complication.

  1. Isolation and characterization of renal erythropoietin-producing cells from genetically produced anemia mice.

    Directory of Open Access Journals (Sweden)

    Xiaoqing Pan

    Full Text Available Understanding the nature of renal erythropoietin-producing cells (REPs remains a central challenge for elucidating the mechanisms involved in hypoxia and/or anemia-induced erythropoietin (Epo production in adult mammals. Previous studies have shown that REPs are renal peritubular cells, but further details are lacking. Here, we describe an approach to isolate and characterize REPs. We bred mice bearing an Epo gene allele to which green fluorescent protein (GFP reporter cDNA was knocked-in (Epo(GFP with mice bearing an Epo gene allele lacking the 3' enhancer (Epo(Δ3'E. Mice harboring the mutant Epo(GFP/Δ3'E gene exhibited anemia (average Hematocrit 18% at 4 to 6 days after birth, and this perinatal anemia enabled us to identify and purify REPs based on GFP expression from the kidney. Light and confocal microscopy revealed that GFP immunostaining was confined to fibroblastic cells that reside in the peritubular interstitial space, confirming our previous observation in Epo-GFP transgenic reporter assays. Flow cytometry analyses revealed that the GFP fraction constitutes approximately 0.2% of the whole kidney cells and 63% of GFP-positive cells co-express CD73 (a marker for cortical fibroblasts and Epo-expressing cells in the kidney. Quantitative RT-PCR analyses confirmed that Epo expression was increased by approximately 100-fold in the purified population of REPs compared with that of the unsorted cells or CD73-positive fraction. Gene expression analyses showed enrichment of Hif2α and Hif3α mRNA in the purified population of REPs. The genetic approach described here provides a means to isolate a pure population of REPs, allowing the analysis of gene expression of a defined population of cells essential for Epo production in the kidney. This has provided evidence that positive regulation by HIF2α and negative regulation by HIF3α might be necessary for correct renal Epo induction.

  2. Renal cell tumour characteristics in patients with the Birt-Hogg-Dubé cancer susceptibility syndrome: a retrospective, multicentre study.

    Science.gov (United States)

    Benusiglio, Patrick R; Giraud, Sophie; Deveaux, Sophie; Méjean, Arnaud; Correas, Jean-Michel; Joly, Dominique; Timsit, Marc-Olivier; Ferlicot, Sophie; Verkarre, Virginie; Abadie, Caroline; Chauveau, Dominique; Leroux, Dominique; Avril, Marie-Françoise; Cordier, Jean-François; Richard, Stéphane

    2014-10-29

    The Birt-Hogg-Dubé syndrome is a rare cancer susceptibility syndrome characterised by renal tumours, lung cysts and pneumothoraces, and fibrofolliculomas. It is caused by dominantly inherited mutations in FLCN. Our objective was to report renal tumour characteristics in a large series of patients with the Birt-Hogg-Dubé syndrome. We studied French Birt-Hogg-Dubé patients with a history of renal tumour. We included 33 patients with 21 distinct germline FLCN mutations. Median age at diagnosis of first renal tumour was 46, and age varied from 20 to 83. Twenty cases had one renal tumour, the remainder had two or more tumours. Most cases (23/33, 70%) had oncocytoma or renal cell carcinoma of the chromophobe or hybrid chromophobe-oncocytoma type, three had clear cell carcinoma (9%), and the other seven had carcinoma of papillary, undifferentiated or undetermined histology. Four cases had metastatic disease, although none died of it. Age at renal tumour diagnosis was highly variable, highlighting the need for regular surveillance from young adulthood to old age. Most cases had tumour types classically associated with Birt-Hogg-Dubé, i.e. oncocytoma or renal cell carcinoma of the chromophobe or hybrid type. Nevertheless, 9% had clear cell renal cell carcinoma. Geneticists, urologists and oncologists should therefore be alert to the possibility of Birt-Hogg-Dubé in patients with renal cell carcinoma of clear cell histology, especially if there are associated manifestations. Finally, the behaviour of metastatic carcinoma seemed more indolent than in sporadic renal cancers.

  3. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment.

    Science.gov (United States)

    Zuo, Li; Tozawa, Keiichi; Okada, Atsushi; Yasui, Takahiro; Taguchi, Kazumi; Ito, Yasuhiko; Hirose, Yasuhiko; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Ando, Ryosuke; Itoh, Yasunori; Zou, Jiangang; Kohri, Kenjiro

    2014-06-01

    We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation. Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells. Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series.

    Science.gov (United States)

    Brinkerhoff, Brian T; Houghton, Donald C; Troxell, Megan L

    2016-06-01

    Renal injury in hematopoietic cell transplant recipients may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease, and can involve glomerular, tubulointerstitial, and vascular structures. We reviewed renal pathology from 67 patients at a single institution (2009-2014), including 14 patients with biopsy for clinical dysfunction, 6 patients with surgical kidney resection for other causes, and 47 autopsy patients. Kidney specimens frequently contained multiple histopathologic abnormalities. Thrombotic microangiopathy, membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis were the most common glomerular findings. Pathologies not previously reported in the hematopoietic cell transplant setting included collapsing glomerulopathy, antiglomerular basement membrane disease, fibrillary glomerulonephritis, and in the case of two surgical resections distinctive cellular segmental glomerular lesions that defied classification. Kidney specimens frequently demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, and arteriosclerosis. Other kidney findings at autopsy included leukemia and amyloid (both recurrent), diabetic nephropathy, bacterial infection, fungal invasion, and silver deposition along glomerular and tubular basement membranes. Also in the autopsy cohort, C4d immunohistochemistry demonstrated unexpected membranous nephropathy in two patients, yet C4d also colocalized with arteriolar hyaline. This retrospective hematopoietic cell transplant cohort illustrates multifaceted renal injury in patients with renal dysfunction, as well as in patients without clinically recognized kidney injury.

  5. 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.

  6. microRNA-183 plays as oncogenes by increasing cell proliferation, migration and invasion via targeting protein phosphatase 2A in renal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Mingning, E-mail: lcuzfy@163.com; Liu, Lei, E-mail: leiliulab@163.com; Chen, Lieqian, E-mail: lieqianchen@163.com; Tan, Guobin, E-mail: guobintan@163.com; Liang, Ziji, E-mail: zijilianglab@163.com; Wang, Kangning, E-mail: kangningwanglab@163.com; Liu, Jianjun, E-mail: jianjunliulab@163.com; Chen, Hege, E-mail: hegechen@163.com

    2014-09-12

    Highlights: • miR-183 was up-regulated in renal cancer tissues. • Inhibition of endogenous miR-183 suppressed renal cancer cell growth and metastasis. • miR-183 increased cell growth and metastasis. • miR-183 regulated renal cancer cell growth and metastasis via directly targeting tumor suppressor protein phosphatase 2A. - Abstract: The aim of this study was to investigate the function of miR-183 in renal cancer cells and the mechanisms miR-183 regulates this process. In this study, level of miR-183 in clinical renal cancer specimens was detected by quantitative real-time PCR. miR-183 was up- and down-regulated in two renal cancer cell lines ACHN and A498, respectively, and cell proliferation, Caspase 3/7 activity, colony formation, in vitro migration and invasion were measured; and then the mechanisms of miR-183 regulating was analyzed. We found that miR-183 was up-regulated in renal cancer tissues; inhibition of endogenous miR-183 suppressed in vitro cell proliferation, colony formation, migration, and invasion and stimulated Caspase 3/7 activity; up-regulated miR-183 increased cell growth and metastasis and suppressed Caspase 3/7 activity. We also found that miR-183 directly targeted tumor suppressor, specifically the 3′UTR of three subunits of protein phosphatase 2A (PP2A-Cα, PP2A-Cβ, and PP2A-B56-γ) transcripts, inhibiting their expression and regulated the downstream regulators p21, p27, MMP2/3/7 and TIMP1/2/3/4. These results revealed the oncogenes role of miR-183 in renal cancer cells via direct targeting protein phosphatase 2A.

  7. Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor lysate

    DEFF Research Database (Denmark)

    Soleimani, A; Berntsen, A; Svane, I M

    2009-01-01

    Patients with metastatic renal cell carcinoma (mRCC) have a limited life expectancy but still a subset of these patients develop immune and clinical responses after immunotherapy including dendritic cell (DC) vaccination. In a recently published phase I/II trials, fourteen HLA-A2 negative patients...... with progressive mRCC were vaccinated with autologous DC pulsed with allogeneic tumour lysate. Low-dose IL-2 administered subcutaneously was given concomitantly. In this study, we analysed lysate specific proliferation of PBMCs from these patients together with the TH1/TH2 balance of the responding T cells. Also......, serum concentrations of IL-10, IL-12, IL-15, IL-17 and IL-18 from these patients and additional thirteen HLA-A2 positive mRCC patients treated with autologous DC pulsed with survivin and telomerase peptides were analysed during vaccination to identify systemic immune responses and potential response...

  8. 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.

  9. Metastatic Renal Cell Carcinoma: The Importance of Immunohistochemistry in Differential Diagnosis

    Directory of Open Access Journals (Sweden)

    Sandra Custódio

    2012-01-01

    Full Text Available Introduction: Clear cell carcinoma accounts for 75% of all types of renal neoplasms. Approximately one third presents with metastatic disease at diagnosis. Immunohistochemical studies play a significant diagnostic role. Case Report: We report the case of a 48-year-old heavy smoker who presented with productive cough and progressive dyspnea. The study revealed a renal mass and lung alterations compatible with primary tumor of the lung. The patient underwent a right complete nephrectomy. The anatomopathological exam showed clear cell renal carcinoma (pT1bN0Mx. After transthoracic needle aspiration biopsy, the clinical diagnosis was stage IV adenocarcinoma of the lung. Initially, the patient received one cycle of chemotherapy (cisplatin/pemetrexed. Two weeks later, the immunohistochemistry tests revealed a secondary lesion with probable renal origin. Chemotherapy was stopped and the patient was started on sunitinib treatment. After two cycles the disease progressed. A second-line treatment with everolimus was proposed; however, the patient died 2 weeks later due to terminal respiratory insufficiency. Discussion: Clear cell renal cell carcinoma remains one of the great mimickers in pathology. Immunohistochemistry is a valuable tool in the differential diagnosis of lung carcinomas. With the help of thyroid transcription factor 1, it is possible to distinguish a primary lung tumor from a metastasis with a reasonable degree of certainty. The present case report illustrates the challenge of making a definitive and adequate diagnosis. The immunohistochemistry added information that changed the whole treatment strategy. For the best treatment approach, it is fundamental that clinicians await all possible test results, before establishing a treatment plan.

  10. 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.)

  11. Preserving the B-Cell Compartment Favors Operational Tolerance in Human Renal Transplantation

    Science.gov (United States)

    Silva, Hernandez M; Takenaka, Maisa C S; Moraes-Vieira, Pedro M M; Monteiro, Sandra M; Hernandez, Maristela O; Chaara, Wahiba; Six, Adrien; Agena, Fabiana; Sesterheim, Patrícia; Barbé-Tuana, Florencia Maria; Saitovitch, David; Lemos, Francine; Kalil, Jorge; Coelho, Verônica

    2012-01-01

    Transplanted individuals in operational tolerance (OT) maintain long-term stable graft function after completely stopping immunosuppression. Understanding the mechanisms involved in OT can provide valuable information about pathways to human transplantation tolerance. Here we report that operationally tolerant individuals display quantitative and functional preservation of the B-cell compartment in renal transplantation. OT exhibited normal numbers of circulating total B cells, naive, memory and regulatory B cells (Bregs) as well as preserved B-cell receptor repertoire, similar to healthy individuals. In addition, OT also displayed conserved capacity to activate the cluster of differentiation 40 (CD40)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in Bregs, in contrast, with chronic rejection. Rather than expansion or higher activation, we show that the preservation of the B-cell compartment favors OT. PMID:22252714

  12. Mast cells in renal inflammation and fibrosis: lessons learnt from animal studies.

    Science.gov (United States)

    Madjene, Lydia Celia; Pons, Maguelonne; Danelli, Luca; Claver, Julien; Ali, Liza; Madera-Salcedo, Iris K; Kassas, Asma; Pellefigues, Christophe; Marquet, Florian; Dadah, Albert; Attout, Tarik; El-Ghoneimi, Alaa; Gautier, Gregory; Benhamou, Marc; Charles, Nicolas; Daugas, Eric; Launay, Pierre; Blank, Ulrich

    2015-01-01

    Mast cells are hematopoietic cells involved in inflammation and immunity and have been recognized also as important effector cells in kidney inflammation. In humans, only a few mast cells reside in kidneys constitutively but in progressive renal diseases their numbers increase substantially representing an essential part of the interstitial infiltrate of inflammatory cells. Recent data obtained in experimental animal models have emphasized a complex role of these cells and the mediators they release as they have been shown both to promote, but also to protect from disease and fibrosis development. Sometimes conflicting results have been reported in similar models suggesting a very narrow window between these activities depending on the pathophysiological context. Interestingly in mice, mast cell or mast cell mediator specific actions became also apparent in the absence of significant mast cell kidney infiltration supporting systemic or regional actions via draining lymph nodes or kidney capsules. Many of their activities rely on the capacity of mast cells to release, in a timely controlled manner, a wide range of inflammatory mediators, which can promote anti-inflammatory actions and repair activities that contribute to healing, but in some circumstances or in case of inappropriate regulation may also promote kidney disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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

  14. Increase of Circulating CD4(+)CD25(high)Foxp3(+) Regulatory T Cells in Patients With Metastatic Renal Cell Carcinoma During Treatment With Dendritic Cell Vaccination and Low-Dose Interleukin-2

    DEFF Research Database (Denmark)

    Berntsen, Annika; Brimnes, M.K.; Straten, P.T.

    2010-01-01

    in patients with metastatic renal cell carcinoma on the frequency of CD4(+) CD25(high)Foxp3(+) Treg cells in peripheral blood. We found that the treatment increased the frequency of Treg cells more than 7-fold compared with pretreatment levels (P ... to an increase in the number of Treg cells whereas IL-21 does not stimulate the induction of Treg cells. These findings demonstrate that even low doses of IL-2 in combination with DC vaccination are able to expand CD4(+)CD25(+)Foxp3(+) Treg cells in vivo in metastatic renal cell carcinoma patients. Further...

  15. Primary mediastinal large B-cell lymphoma arising from thyroid in a renal recipient with Hashimoto’s thyroiditis

    OpenAIRE

    Wu, Fang; Qu, Lu; Li, Dai-Qiang; Hu, Chun-Hong

    2015-01-01

    Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, arising in the mediastinum from putative thymic B-cell origin with distinctive clinical and genetic features. Generally, primary mediastinal large B-cell lymphoma is believed as only deriving in the mediastinum. The current study presents a rare case of primary mediastinal large B-cell lymphoma which arising from thyroid in a renal recipient with Hashimoto’s thyroiditis. Moreover, we devoted a discussion ...

  16. Potential of stem/progenitor cell cultures within polyester fleeces to regenerate renal tubules.

    Science.gov (United States)

    Roessger, Anne; Denk, Lucia; Minuth, Will W

    2009-08-01

    The cell biological mechanism controlling the regeneration of renal tubules in renal failure after application of stem/progenitor cells is subject of actual research. Unsolved issues are the integration of stem/progenitor cells in a diseased organ environment, the differentiation into epithelial tissue and the formation of tubules in a spatial environment. Following this therapeutic strategy new biomaterials have to be found promoting spatial development of tubules. To obtain new information about the growth of tubules renal stem/progenitor cells from neonatal rabbit kidney were isolated and mounted in a tissue carrier between a selection of commercially available polyester fleeces. This procedure replaces coating by extracellular matrix proteins and creates an artificial interstitium supporting development of tubules. Perfusion culture was performed with chemically defined IMDM containing aldosterone as tubulogenic factor. Polyester fleeces were investigated by scanning electron microscopy. The spatial development of tubules was registered on whole-mount specimens and on cryosections labeled with SBA and antibodies indicating tubule differentiation. It is found that some polyester fleeces promote the spatial development of tubules between the fibers, whereat each of them produces its individual growth pattern.

  17. MicroRNAs and their target gene networks in renal cell carcinoma

    International Nuclear Information System (INIS)

    Redova, Martina; Svoboda, Marek; Slaby, Ondrej

    2011-01-01

    Research highlights: → MiRNAs are related to the processes of cell proliferation, apoptosis, angiogenesis, invasion, and metastasis in RCC. → MiRNAs expression profiles are associated with several RCC-specific genetic alterations. → It has been well documented that several miRNAs are downstream effector molecules of the HIF-induced hypoxia response. → MiR-200 family is linked to epithelial-mesenchymal transition which is one of the most significant pathogenetic mechanism in RCC. → Mechanistic studies in RCC have provided the rationale of using miRNAs as potential therapeutic targets. -- Abstract: MicroRNAs (miRNAs) are non-protein-coding short single stranded RNAs in the size range 19-25 nucleotides that are associated with gene regulation at the transcriptional and translational level. Recent studies have proved that miRNAs play important roles in a large number of biological processes, including cellular differentiation, proliferation, apoptosis, etc. Changes in their expression were found in a variety of human cancers, including renal cell carcinoma pathogenesis. Specific miRNA alterations were associated with key pathogenetic mechanisms of renal cell carcinoma like hypoxia or epithelial-mesenchymal transition. In this review, we summarize the current knowledge of miRNA functions in renal cell carcinoma with an emphasis on miRNAs potential to serve as a powerful biomarker of disease and a novel therapeutic target in oncology.

  18. Metastasis of renal cell carcinoma to the thyroid gland 19 years after nephrectomy: a case report.

    Science.gov (United States)

    Kihara, Minoru; Yokomise, Hiroyasu; Yamauchi, Akira

    2004-03-01

    Although metastases to the thyroid are never uncommon at autopsy in patients who died of malignancy, metastatic thyroid carcinomas are rarely detected in clinical practice in most cases and cases of secondary thyroid cancer which require thyroid surgery clinically are few. A clinical case of thyroid metastasis from renal cell carcinoma with thyroidectomy is described herein. An 87-year-old Japanese woman was referred to us for a slow-growing palpable neck tumor with dysphagia. She had undergone a nephrectomy for renal clear cell carcinoma 19 years earlier at another hospital. Preoperative imaging examinations suspected an adenomatous goiter and a fine needle aspiration (FNA) cytology was suggestive of an atypical follicular tumor. Hemithyroidectomy was performed as a follicular tumor of thyroid for restriction of subjective symptom. A pathological examination of the thyroid tumor revealed clear cell carcinoma, postoperatively. The negative result of immunohistochemical staining for thyroglobulin also suggested metastatic renal cell carcinoma to the thyroid. Clinically significant metastases to the thyroid gland are relatively infrequent. However, if patient who bears a thyroid tumor has a history of malignancy, the possibility of metastatic disease should be taken under consideration.

  19. 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.

  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. Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

    Directory of Open Access Journals (Sweden)

    Fong Kah

    2011-04-01

    Full Text Available Abstract Introduction Laparoscopic port-site metastasis is a rare but well recognized outcome following surgery in urological cancers, with its etiology not clearly understood. Additionally, vaginal metastasis in clear cell renal cell carcinoma is rare, and has not been previously reported in the setting of papillary renal cell carcinoma. Case presentation We present the case of a 71-year-old Chinese woman with metastatic type II papillary renal cell carcinoma with histologically verified vaginal involvement and a concurrent laparoscopic port-site metastasis. This was also associated with a unique constellation of widely disseminated metastatic sites, which include a local relapse, the peritoneum and the urethra. Conclusion Laparoscopic port-site metastases are associated with the presence of advanced cancer with multiple sites of metastasis. We hypothesize from the findings of our report and background data that this phenomenon is more likely to be related to tumor factors rather than operative factors. We also present what is, to the best of our knowledge, the first reported case in the literature of vaginal and urethral metastasis and the second reported case of laparoscopic port-site recurrence.

  3. 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)

  4. End-stage renal disease causes skewing in the TCR Vβ-repertoire primarily within CD8+ T Cell subsets

    NARCIS (Netherlands)

    L. Huang (Ling); M.G.H. Betjes (Michiel); M. Klepper (Mariska); A.W. Langerak (Anton); C.C. Baan (Carla); N.H.R. Litjens (Nicolle)

    2017-01-01

    textabstractA broad T cell receptor (TCR-) repertoire is required for an effective immune response. TCR-repertoire diversity declines with age. End-stage renal disease (ESRD) patients have a prematurely aged T cell system which is associated with defective T cell-mediated immunity. Recently, we

  5. Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena [Instituto De Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by {sup 60}Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found

  6. Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yongchao; Yin, Bingde; Zhang, Changcun; Zhou, Libin [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China); Fan, Jie, E-mail: jief67@sina.com [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer This study is the first to test the let-7a/c-myc loop in renal cell carcinoma cell lines. Black-Right-Pointing-Pointer Let-7a down-regulated c-myc in three renal cell carcinoma cell lines. Black-Right-Pointing-Pointer c-myc target genes were down-regulated because of the let-7a-mediated down-regulation of c-myc. Black-Right-Pointing-Pointer The let-7a/c-myc loop has a significant function in renal cell carcinoma cell lines. -- Abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

  7. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways.

    Science.gov (United States)

    Nagai, Junya; Takano, Mikihisa

    2014-08-15

    Aminoglycoside antibiotics such as gentamicin and amikacin are well recognized as a clinically important antibiotic class because of their reliable efficacy and low cost. However, the clinical use of aminoglycosides is limited by their nephrotoxicity and ototoxicity. Nephrotoxicity is induced mainly due to high accumulation of the antibiotics in renal proximal tubular cells. Therefore, a lot of studies on characterization of the renal transport system for aminoglycosides so far reported involved various in-vivo and in-vitro techniques. Early studies revealed that aminoglycosides are taken up through adsorptive endocytosis in renal epithelial cells. Subsequently, it was found that megalin, a multiligand endocytic receptor abundantly expressed on the apical side of renal proximal tubular cells, can bind aminoglycosides and that megalin-mediated endocytosis plays a crucial role in renal accumulation of aminoglycosides. Therefore, megalin has been suggested to be a promising molecular target for the prevention of aminoglycoside-induced nephrotoxicity. On the other hand, recently, some reports have indicated that aminoglycosides are transported via a pathway that does not require endocytosis, such as non-selective cation channel-mediated entry, in cultured renal tubular cells as well as cochlear outer hair cells. In this commentary article, we review the cellular transport of aminoglycosides in renal epithelial cells, focusing on endocytosis-dependent and -independent pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. 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

  9. Haploidentical hematopoietic SCT increases graft-versus-tumor effect against renal cell carcinoma.

    Science.gov (United States)

    Budak-Alpdogan, T; Sauter, C T; Bailey, C P; Biswas, C S; Panis, M M; Civriz, S; Flomenberg, N; Alpdogan, O

    2013-08-01

    Allogeneic hematopoietic SCT (HSCT) has been shown to be an effective treatment option for advanced renal cell cancer (RCC). However, tumor resistance/relapse remains as the main post transplant issue. Therefore, enhancing graft-versus-tumor (GVT) activity without increasing GVHD is critical for improving the outcome of HSCT. We explored the GVT effect of haploidentical-SCT (haplo-SCT) against RCC in murine models. Lethally irradiated CB6F1 (H2K(b/d)) recipients were transplanted with T-cell-depleted BM cells from B6CBAF1 (H2K(b/k)) mice. Haplo-SCT combined with a low-dose haploidentical (HI) T-cell infusion (1 × 10(5)) successfully provided GVT activity without incurring GVHD. This effect elicited murine RCC growth control and consequently displayed a comparative survival advantage of haplo-SCT recipients when compared with MHC-matched (B6D2F1CB6F1) and parent-F1 (B6CB6F1) transplant recipients. Recipients of haplo-SCT had an increase in donor-derived splenic T-cell numbers, T-cell proliferation and IFN-γ-secreting donor-derived T-cells, a critical aspect for anti-tumor activity. The splenocytes from B6CBAF1 mice had a higher cytotoxicity against RENCA cells than the splenocytes from B6 and B6D2F1 donors after tumor challenge. These findings suggest that haplo-SCT might be an innovative immunotherapeutic platform for solid tumors, particularly for renal cell carcinoma.

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

    Science.gov (United States)

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

    2017-11-01

    Aspartame is widely used artificial sweeteners as food additives. Several researchers have pointed that the controversial report on the use of aspartame over more than decades. Omega-3 fatty acids are essential and unsaturated fatty acids, and it plays a remarkable role in vision, intelligence, neural development, and metabolism of neurotransmitters. Therefore, the present study was aimed to investigate the effect of omega-3 fatty acids on aspartame treated renal cells. Experimental groups were divided into three such as sham control, aspartame treated, and aspartame with omega-3 fatty acids. Cell viability was determined by sulforhodamine-b assay and flow cytometric analysis. The experimental results showed that the aspartame induced altered cell viability were reduced following treatment of aspartame with omega-3 fatty acids. Altered cell morphology was recovered by omega-3 fatty acids. DNA damage appeared in the highest concentration of aspartame used in this study. DNA damage characteristics such as comet tail and tiny head sections did not appear in the omega-3 fatty acids treated cells. Several microvilli and vesicular structures were found in aspartame treated cells. Altered morphology such as rounding, microvilli, and formation of dome-like structures did not appear in the omega-3 fatty acids with aspartame treated cells. Caspase-3 mRNA and protein expression were increased in aspartame treated cells, and these levels were reduced following omega-3 fatty acids treatment. Taking all these data together, it is suggested that the omega-3 fatty acids may be a therapeutic agent to reduce the aspartame induced biochemical and morphological alterations in normal renal cells. © 2017 BioFactors, 43(6):847-857, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  11. 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

  12. Relationship of Cell Proliferating Marker Expressions with PGE(2) Receptors in Regenerating Rat Renal Tubules after Cisplatin Injection.

    Science.gov (United States)

    Yamamoto, Emi; Izawa, Takeshi; Juniantito, Vetnizah; Kuwamura, Mitsuru; Yamate, Jyoji

    2010-12-01

    Cisplatin, an anticancer drug, is well known to have nephrotoxicity as an adverse effect. We investigated the expressions of cell cycle markers and prostaglandin E(2) (PGE(2)) receptors (EP) in the affected renal tubules in rats injected with a single dose (6 mg/kg body weight) of cisplatin. On days 1-3 after dosing, the affected renal epithelial cells were almost desquamated, showing necrosis. On day 5 onwards, the renal tubules were rimmed by flattened or cuboidal epithelial cells with basophilic cytoplasm; BrdU-immunopositive cells began to significantly increase, indicating regeneration. Simultaneously, TUNEL-positive apoptotic cells were also seen. On days 1-5, cyclin D1-immunopositive cells were decreased with an increased expression in p21 mRNA, indicating G(1) arrest in the cell cycle. The affected renal epithelial cells began to react to EP4 receptor, but not to EP2 receptor. Some EP4 receptor-reacting epithelial cells gave a positive reaction to BrdU or cyclin D1. Collectively, the affected renal tubules underwent various alterations such as necrosis, apoptosis, regeneration and G(1) arrest; the aspects might be influenced by endogenous PGE(2) through EP4 receptor.

  13. The plant-derived natural compound Flavin 7 attenuates oxidative stress in cultured renal proximal tubule cells.

    Science.gov (United States)

    Ember, Agoston; Clark, Jeb S; Varjas, Timea; Kiss, Istvan; Ember, Istvan; Baliga, Radhakrishna; Arany, Istvan

    2009-01-01

    Cancer therapies and cancer progression can increase oxidative stress that might account for renal toxicity in cancer patients. Flavin 7 (F7) is a natural polyphenol-containing dietary supplement with potential antioxidant activity. Therefore, it might help to attenuate renal toxicity of chemotherapeutics. Cultured mouse renal proximal tubule cells were subjected to H(2)O(2)-mediated oxidative stress. Potential antioxidant effects of F7 were assessed by measuring the production of reactive oxygen species (ROS), mitochondrial depolarization and injury (lactate dehydrogenase release as well as trypan blue exclusion) in cells that were pretreated with F7 prior to treatment with H(2)O(2). F7 pretreatment significantly attenuated H(2)O(2)-induced ROS production, mitochondrial depolarization and consequent injury in renal proximal tubule cells. F7 supplementation might be beneficial for cancer patients in order to prevent renal toxicity of anticancer drug- or cancer progression-related oxidative stress.

  14. In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients

    International Nuclear Information System (INIS)

    Walle, A.J.; Wong, G.Y.; Suthanthiran, M.; Rubin, A.L.; Stenzel, K.H.

    1988-01-01

    High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3 H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo

  15. Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma.

    Science.gov (United States)

    Yamamoto, Kazuhiro; Yano, Ikuko

    2018-01-04

    The prognosis of patients with metastatic renal cell carcinoma has drastically improved due to the development of molecular-targeted drugs and their use in clinical practice. However, these drugs cause some diverse adverse reactions in patients and sometimes affect clinical outcomes of cancer therapy. Therefore, predictive markers are necessary to avoid severe adverse reactions, to establish novel and effective prevention methods, and to improve treatment outcomes. Some genetic factors involved in these adverse reactions have been reported; however, perspectives on each adverse response have not been integrated yet. In this review, genetic polymorphisms relating to molecular-targeted therapy-induced adverse reactions in patients with renal cell carcinoma are summarized in the points of pharmacokinetic and pharmacodynamic mechanisms. We also discuss about the relationship between systemic drug exposure and adverse drug reactions.

  16. 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.

  17. Metastasis from renal cell carcinoma to thyroid presenting as rapidly growing neck mass.

    Science.gov (United States)

    Mohammadi, Afshin; Toomatari, Seyed Babak Mosavi; Ghasemi-Rad, Mohammad

    2014-01-01

    Renal cell carcinoma (RCC) is commonly known as the "internist's tumor" because of its unpredictable behavior. Metastasis to the thyroid gland is rarely found in clinical practice. We report a rare case of non-thyroid malignancies NTM from renal cell carcinoma 1.5 years after radical nephrectomy in a 58-year-old man with a rapidly growing neck mass. Malignant melanoma, breast carcinoma, lung, and skin cancer are the most common sources of non-thyroid malignancies (NTM). Although metastases of NTMs to the thyroid gland are uncommon in clinical practice, it should be considered in patients with a history of prior malignancy and a new thyroid mass. Isolated thyroid metastasis should be considered in patients with a previous history of cancer and newly developing thyroid mass. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Solitary intrathyroidal metastasis of renal clear cell carcinoma in a toxic substernal multinodular goiter

    Directory of Open Access Journals (Sweden)

    Dionigi Gianlorenzo

    2008-10-01

    Full Text Available Abstract Introduction Thyroid gland is a rare site of clinically detectable tumor metastasis. Case report A 71-year-old woman was referred to our department for an evaluation of toxic multinodular substernal goiter. She had a history of renal clear cell carcinoma of the left kidney, which had been resected 2 years previously. US confirmed the multinodular goiter. Total thyroidectomy with neuromonitoring was performed on March 2008. A histological examination revealed a solitary metastasis of a clear cell renal cancer in a diffuse multinodular goiter. No distant metastases are detected. Conclusion Although uncommon, it is important for the endocrine surgeon and endocrine oncologist to be able to recognize and differentiate intrathyroid metastases from more primary common thyroid neoplasms. The diagnosis can be suspected if the patient has a thyroid tumor and a past history of extrathyroid cancer. These tumors, on the whole, tend to behave more aggressively and, in most cases, the use of multimodality therapy is recommended.

  19. Squamous cell carcinoma of skin after 20 years of renal transplantation

    Directory of Open Access Journals (Sweden)

    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.

  20. Renal Cell Carcinoma of Contralateral Kidney with Secondaries in Gallbladder Eight Years After Nephrectomy

    Directory of Open Access Journals (Sweden)

    Kechrid Mohamed

    2000-01-01

    Full Text Available A 55-year-old female underwent right nephrectomy for renal cell carcinoma (RCC. The histopathology showed clear cell carcinoma. There was no evidence of metastasis. After remaining asymptomatic for eight years, she developed pain in the right loin. Abdominal ultrasound, computerized tomography (CT Scan and magnetic resonance imaging (MRI were suggestive of a tumor mass in the right renal area, multiple tumor masses in the left kidney and a mass in the gallbladder. Cholecystectomy, left radical nephrectomy and right adrenal mass with excision of adjacent lymph nodes were performed. The histopathology from all sites was suggestive of RCC. She was maintained on hemodialysis. Two and half years later she died after surgical exploration for spinal cord decompression due to metastasis to the dorsal spine.

  1. Acute cor pulmonale due to pulmonary tumour thrombotic microangiopathy from renal cell carcinoma.

    Science.gov (United States)

    Story, Maria; Kwon, Sook Kyung; Robinson, Robert; Fortis, Spyridon

    2017-06-28

    We report the case of a previously healthy man who presented with subacute dyspnoea after a long drive. He developed hypoxic respiratory failure, thought secondary to a massive pulmonary embolism and was treated with tissue plasminogen activator but died in the hospital despite aggressive medical measures. Autopsy revealed pulmonary tumour thrombotic microangiopathy (PTTM) from papillary renal cell carcinoma. PTTM is a rare clinicopathological syndrome that clinically results in symptoms of dyspnoea and right heart failure. Pathologically, a localised paraneoplastic process evolves from tumour microemboli in the pulmonary arterioles, resulting in fibrocellular proliferation and narrowing of the vessels, causing subacute right heart failure. To our knowledge, this is the first case of PTTM due to papillary renal cell carcinoma. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Megan G Massa

    Full Text Available As multiple sclerosis research progresses, it is pertinent to continue to develop suitable paradigms to allow for ever more sophisticated investigations. Animal models of multiple sclerosis, despite their continuing contributions to the field, may not be the most prudent for every experiment. Indeed, such may be either insufficient to reflect the functional impact of human genetic variations or unsuitable for drug screenings. Thus, we have established a cell- and patient-specific paradigm to provide an in vitro model within which to perform future genetic investigations. Renal proximal tubule epithelial cells were isolated from multiple sclerosis patients' urine and transfected with pluripotency-inducing episomal factors. Subsequent induced pluripotent stem cells were formed into embryoid bodies selective for ectodermal lineage, resulting in neural tube-like rosettes and eventually neural progenitor cells. Differentiation of these precursors into primary neurons was achieved through a regimen of neurotrophic and other factors. These patient-specific primary neurons displayed typical morphology and functionality, also staining positive for mature neuronal markers. The development of such a non-invasive procedure devoid of permanent genetic manipulation during the course of differentiation, in the context of multiple sclerosis, provides an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery.

  3. Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo.

    Directory of Open Access Journals (Sweden)

    Lakshmipathi Khandrika

    Full Text Available Oxalate is a metabolic end product excreted by the kidney. Mild increases in urinary oxalate are most commonly associated with Nephrolithiasis. Chronically high levels of urinary oxalate, as seen in patients with primary hyperoxaluria, are driving factor for recurrent renal stones, and ultimately lead to renal failure, calcification of soft tissue and premature death. In previous studies others and we have demonstrated that high levels of oxalate promote injury of renal epithelial cells. However, methods to monitor oxalate induced renal injury are limited. In the present study we evaluated changes in expression of Kidney Injury Molecule-1 (KIM-1 in response to oxalate in human renal cells (HK2 cells in culture and in renal tissue and urine samples in hyperoxaluric animals which mimic in vitro and in vivo models of hyper-oxaluria. Results presented, herein demonstrate that oxalate exposure resulted in increased expression of KIM-1 m RNA as well as protein in HK2 cells. These effects were rapid and concentration dependent. Using in vivo models of hyperoxaluria we observed elevated expression of KIM-1 in renal tissues of hyperoxaluric rats as compared to normal controls. The increase in KIM-1 was both at protein and mRNA level, suggesting transcriptional activation of KIM-1 in response to oxalate exposure. Interestingly, in addition to increased KIM-1 expression, we observed increased levels of the ectodomain of KIM-1 in urine collected from hyperoxaluric rats. To the best of our knowledge our studies are the first direct demonstration of regulation of KIM-1 in response to oxalate exposure in renal epithelial cells in vitro and in vivo. Our results suggest that detection of KIM-1 over-expression and measurement of the ectodomain of KIM-1 in urine may hold promise as a marker to monitor oxalate nephrotoxicity in hyperoxaluria.

  4. Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    was inhibited by buffering of intracellular calcium with BAPTA, by the antioxidant N-acetylcysteine and by uncoupling of mitochondrial oxidative phosphorylation from respiration with CCCP. These results indicate that Cd generate a prompt initiation of ROS production from mitochondria due to an increase......Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells. Henning F. Bjerregaard, Roskilde University, Department of Science, Systems and Models , 4000 Roskilde, Denmark. HFB@ RUC.DK Reactive oxygen species (ROS) like, hydrogen...... dynamics in living cells in response to hormonal signal events in the A6 cell culture. A6 cells have a divalent cation-sensing receptor (the extracellular calcium receptor) that can be stimulated with cadmium (Cd) and thereby induce a fast and transient liberation of calcium from intracellular stores, due...

  5. Coexistence Between Hodgkin’s Lymphoma and Renal Cell Cancer: Case Report

    Directory of Open Access Journals (Sweden)

    Mustafa Karabıçak

    2014-11-01

    Full Text Available Renal cell cancer (RCC is the most common kidney tumor and accounts for 3% of all adult cancers. Hodgkin’s lymphoma (HL is also constitutes less than 1% of all malignancies with the male predominance. The risk of secondary cancer increases during the treatment period of HL in 15 years of followup. We presented a case indicating co-occurence between HL and RCC and literature review about this rare coincidence.

  6. Signaling pathways and late-onset gene induction associated with renal mesangial cell hypertrophy

    OpenAIRE

    Goruppi, Sandro; Bonventre, Joseph V.; Kyriakis, John M.

    2002-01-01

    In chronic diseases such as diabetes mellitus, continuous stress stimuli trigger a persistent, self-reinforcing reprogramming of cellular function and gene expression that culminates in the pathological state. Late-onset, stable changes in gene expression hold the key to understanding the molecular basis of chronic diseases. Renal failure is a common, but poorly understood complication of diabetes. Diabetic nephropathy begins with mesangial cell hypertrophy and hyperplasia, combined with exce...

  7. 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.

  8. 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.

  9. Metastatic Renal Cell Cancer to Thyroid Diagnosed by Endoscopic Ultrasound Guided Fine Needle Aspiration Technique

    OpenAIRE

    Abdel-Aziz, Yousef; Hammad, Tariq; Nawras, Mohamad; Abdulwahid, Hayder; Nawras, Ali

    2017-01-01

    Medical literature about the role of endoscopic ultrasound (EUS) in identifying thyroid lesions is limited. We present a case of secondary thyroid cancer from renal cell carcinoma (RCC) metastasis, diagnosed by thyroid EUS-fine needle aspiration (FNA) approach that was done for staging of esophageal adenocarcinoma, in a patient with 11-year history of complete right nephrectomy for RCC. An 81-year-old female patient underwent EUS for the evaluation of a newly discovered distal esophageal canc...

  10. Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy.

    Science.gov (United States)

    Czajka, Anna; Malik, Afshan N

    2016-12-01

    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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. A rare case of synchronous renal cell carcinoma of the bladder presenting with gross hematuria

    Directory of Open Access Journals (Sweden)

    Stephan Kruck

    2013-05-01

    Full Text Available A 57-year old man was referred to the Urology Department due to gross hematuria; abdominal ultrasound revealed an unspecific solid tumor of the left bladder wall. Ultrasound, transurethral resection of the bladder mass with subsequent histological analysis, thoracic and abdominal computed tomography-scan and brain magnetic resonance imaging were performed. He was diagnosed with a bladder metastasis of clear cell renal cell carcinoma (RCC with concomitant bone, pulmonary, and cerebral metastatic disease of a primary RCC of the right kidney. Management: Transurethral resection of the bladder mass, cerebral and bone radiotherapy, removal of the primary tumor, targeted systemic therapy with mTOR followed by tyrosine kinase inhibition.

  12. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

    International Nuclear Information System (INIS)

    Taub, Mary

    2016-01-01

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10 −5  M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  13. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

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    Taub, Mary, E-mail: biochtau@buffalo.edu

    2016-03-11

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  14. Renal transitional cell carcinoma with bilateral ocular metastasis in a cat

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    Irit Grader

    2016-07-01

    Full Text Available Case summary A 4-year-old, spayed female, domestic shorthair cat was presented for evaluation due to a 4 day history of inappetence and lethargy. Physical examination revealed mild dehydration and blindness of the left eye. Abnormal imaging findings included a well-margined soft tissue mass with irregular central cavity located in the dorsal aspect of the caudal lung lobe. Cytological examination of the mass revealed chronic inflammation with hemorrhage. Tests for parasitic and fungal diseases were negative. Ophthalmic examination 17 days after the cat was initially presented revealed severe diffuse pathology of both retinas. Left renomegaly was noted 22 days after the initial presentation, and cytological examination of samples obtained from the right vitreous, left kidney and the pulmonary mass yielded atypical epithelial cells exhibiting malignant changes. Post-mortem examination following euthanasia revealed renal transitional cell carcinoma with metastasis to both eyes, lungs and skeletal muscle. Immunohistochemical evaluation of the neoplastic cells in the eye revealed moderate cytoplasmic reactivity for CK7. CK20 immunohistochemistry was negative. Relevance and novel information To the best of our knowledge, this is the first report of renal transitional cell carcinoma with ocular metastasis in a cat. In addition, this report describes immunohistochemistry results of transitional cell carcinoma in a cat using CK7 and CK20.

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

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    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.

  16. VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.

    Science.gov (United States)

    Bindra, Ranjit S; Vasselli, James R; Stearman, Robert; Linehan, W Marston; Klausner, Richard D

    2002-06-01

    Renal cell carcinoma is associated with mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. Cell lines derived from these tumors cannot exit the cell cycle when deprived of growth factors, and the ability to exit the cell cycle can be restored by the reintroduction of wild-type protein VHL (pVHL). Here, we report that cyclin D1 is overexpressed and remains inappropriately high in during contact inhibition in pVHL-deficient cell lines. In addition, hypoxia increased the expression of cyclin D1 specifically in pVHL-negative cell lines into which pVHL expression was restored. Hypoxic-induction of cyclin D1 was not observed in other pVHL-positive cell lines. This suggests a model whereby in some kidney cell types, pVHL may regulate a proliferative response to hypoxia, whereas the loss of pVHL leads to constitutively elevated cyclin D1 and abnormal proliferation under normal growth conditions.

  17. Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas.

    Science.gov (United States)

    Dengjel, Jörn; Nastke, Maria-Dorothea; Gouttefangeas, Cécile; Gitsioudis, Gitsios; Schoor, Oliver; Altenberend, Florian; Müller, Margret; Krämer, Björn; Missiou, Anna; Sauter, Martina; Hennenlotter, Jörg; Wernet, Dorothee; Stenzl, Arnulf; Rammensee, Hans-Georg; Klingel, Karin; Stevanović, Stefan

    2006-07-15

    To elicit a long-lasting antitumor immune response, CD8+ and CD4+ T cells should be activated. We attempted to isolate HLA-DR-presented peptides directly from dissected solid tumors, in particular from renal cell carcinoma, to identify MHC class II ligands from tumor-associated antigens (TAA) for their use in peptide-based immunotherapy. Tumor specimens were analyzed by immunohistochemical staining for their HLA class II expression. HLA class II peptides were subsequently isolated and identified by mass spectrometry. Gene expression analysis was done to detect genes overexpressed in tumor tissue. Peptides from identified TAAs were used to induce peptide-specific CD4+ T-cell responses in healthy donors and in tumor patients. In the absence of inflammation, expression of MHC class II molecules is mainly restricted to cells of the immune system. To our surprise, we were able to isolate and characterize hundreds of class II peptides directly from primary dissected solid tumors, especially from renal cell carcinomas, and from colorectal carcinomas and transitional cell carcinomas. Infiltrating leukocytes expressed MHC class II molecules and tumor cells, very likely under the influence of IFNgamma. Our list of identified peptides contains ligands from several TAAs, including insulin-like growth factor binding protein 3 and matrix metalloproteinase 7. The latter bound promiscuously to HLA-DR molecules and were able to elicit CD4+ T-cell responses. Thus, our direct approach will rapidly expand the limited number of T-helper epitopes from TAAs for their use in clinical vaccination protocols.

  18. Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells

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    Omar García-Sánchez

    2014-01-01

    Full Text Available Background/Aims: Chronic kidney disease (CKD is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario. Methods: Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ, and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation. Results: We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2 cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability. Conclusion: Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.

  19. Meridional lenticular astigmatism associated with bilateral concurrent uveal metastases in renal cell carcinoma

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    Priluck JC

    2012-11-01

    Full Text Available Joshua C Priluck, Sandeep Grover, KV ChalamDepartment of Ophthalmology, University of Florida College of Medicine, Jacksonville, FL, USAPurpose: To demonstrate a case illustrating meridional lenticular astigmatism as a result of renal cell carcinoma uveal metastases.Methods: Case report with images.Results: Clinical findings and diagnostic testing of a patient with acquired meridional lenticular astigmatism are described. The refraction revealed best-corrected visual acuity of 20/20–1 OD (−2.50 + 0.25 × 090 and 20/50 OS (−8.25 + 3.25 × 075. Bilateral concurrent renal cell carcinoma metastases to the choroid and ciliary body are demonstrated by utilizing ultrasonography, ultrawidefield fluorescein angiography, and unique spectral-domain optical coherence tomography.Conclusions: Metastatic disease should be included in the differential of acquired astigmatism. Spectral-domain optical coherence tomography, ultrawidefield fluorescein angiography, and ultrasonography have roles in delineating choroidal metastases.Keywords: astigmatism, metastasis, optical coherence tomography, renal cell carcinoma

  20. 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.

  1. Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy

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    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

  2. 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.

  3. NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma.

    Science.gov (United States)

    Giesen, Eva; Jilaveanu, Lucia B; Parisi, Fabio; Kluger, Yuval; Camp, Robert L; Kluger, Harriet M

    2014-07-30

    Novel immune therapies targeting tumor specific antigens are being developed. Our purpose was to determine expression of the cancer testes antigen NY-ESO-1 in renal cell carcinoma (RCC), as NY-ESO-1 targeting approaches, particularly adoptive cell therapy, have not been evaluated in this disease. We employed tissue microarrays containing >300 unique RCC cases and adjacent benign renal tissue to determine NY-ESO-1 expression using a quantitative immunofluorescence method. In addition, we studied NY-ESO-1 expression in 35 matched primary and metastatic RCC specimens to assess concordance between different tumor sites. NY-ESO-1 was highly expressed in a subset of RCCs. Expression in primary RCC specimens was significantly higher than adjacent normal renal tissue (PESO-1 expression seen in clear cell RCC suggests that NY-ESO-1 targeting approaches should be studied in this disease. Expression is higher in metastatic sites, and discordance between primary and metastatic sites in some patients suggests that patient selection for these therapies should be based on expression in metastatic rather than nephrectomy specimens.

  4. 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

  5. Renal Cell Carcinoma of 4 cm or Less: An Appraisal of Its Clinical Presentation and Contemporary Surgical Management

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    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.

  6. Recruited renin-containing renal microvascular cells demonstrate the calcium paradox regulatory phenotype

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    MacGriff S

    2014-01-01

    Full Text Available Spencer MacGriff,1 Richard E Woo,1 M Cecilia Ortiz-Capisano,1 Douglas K Atchison,1,2 William H Beierwaltes1,2 1Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, 2Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA Abstract: Renin is the critical regulatory enzyme for production of angiotensin (Ang-II, a potent vasoconstrictor involved in regulating blood pressure and in the pathogenesis of hypertension. Chronic sodium deprivation enhances renin secretion from the kidney, due to recruitment of additional cells from the afferent renal microvasculature to become renin-producing rather than just increasing release from existing juxtaglomerular (JG cells. JG cells secrete renin inversely proportional to extra- and intracellular calcium, a unique phenomenon characteristic of the JG regulatory phenotype known as the “calcium paradox.” It is not known if renin secreted from recruited renin-containing cells is regulated similarly to native JG cells, and therefore acquires this JG cell phenotype. We hypothesized that non-JG cells in renal microvessels recruited to produce renin in response to chronic dietary sodium restriction would demonstrate the calcium paradox, characteristic of the JG cell phenotype. Histology showed recruitment of upstream arteriolar renin in response to sodium restriction compared to normal-diet rats. Renin fluorescence intensity increased 53% in cortices of sodium-restricted rats (P<0.001. We measured renin release from rat afferent microvessels, isolated using iron oxide nanopowder and incubated in either normal or low-calcium media. Basal renin release from normal sodium-diet rat microvessels in normal calcium media was 298.1±44.6 ng AngI/mL/hour/mg protein, and in low-calcium media increased 39% to 415.9±71.4 ng AngI/mL/hour/mg protein (P<0.025. Renin released from sodium-restricted rat microvessels increased 50% compared to samples from

  7. DC-SIGN reacts with TLR-4 and regulates inflammatory cytokine expression via NF-κB activation in renal tubular epithelial cells during acute renal injury.

    Science.gov (United States)

    Feng, D; Wang, Y; Liu, Y; Wu, L; Li, X; Chen, Y; Chen, Y; Chen, Y; Xu, C; Yang, K; Zhou, T

    2018-01-01

    In the pathological process of acute kidney injury (AKI), innate immune receptors are essential in inflammatory response modulation; however, the precise molecular mechanisms are still unclear. Our study sought to demonstrate the inflammatory response mechanisms in renal tubular epithelial cells via Toll-like receptor-4 (TLR-4) and dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin 1 (DC-SIGN) signalling. We found that DC-SIGN exhibited strong expression in renal tubular epithelial cells of human acute renal injury tissues. DC-SIGN protein expression was increased significantly when renal tubular epithelial cells were exposed to lipopolysaccharide (LPS) for a short period. Furthermore, DC-SIGN was involved in the activation of p65 by TLR-4, which excluded p38 and c-Jun N-terminal kinases (JNK). Interleukin (IL)-6 and tumour necrosis factor (TNF)-α expression was decreased after DC-SIGN knock-down, and LPS induced endogenous interactions and plasma membrane co-expression between TLR-4 and DC-SIGN. These results show that DC-SIGN and TLR-4 interactions regulate inflammatory responses in renal tubular epithelial cells and participate in AKI pathogenesis. © 2017 British Society for Immunology.

  8. 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.

  9. 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

    . Immune recognition of autologous TCLs or fresh tumor digests was observed in CD8+ TILs from 82% of patients (18/22). Cytotoxicity assays confirmed the tumoricidal capacity of RCC-TILs. The overall expansion capacity of RCC-TILs was similar to MM-TILs. However, the magnitude, polyfunctionality......-/oligofunctional pattern. The ability to select and expand polyfunctional T cells may improve cell therapy for RCC. Cancer Immunol Res; 1-14. ©2018 AACR....

  10. Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells.

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    Shiyo Muratsu-Ikeda

    Full Text Available BACKGROUND: Oxidative stress and endoplasmic reticulum (ER stress play a crucial role in tubular damage in both acute kidney injury (AKI and chronic kidney disease (CKD. While the pathophysiological contribution of microRNAs (miRNA to renal damage has also been highlighted, the effect of miRNA on renal damage under oxidative and ER stresses conditions remains elusive. METHODS: We assessed changes in miRNA expression in the cultured renal tubular cell line HK-2 under hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was evaluated by cell survival rate, intracellular reactive oxygen species (ROS level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA-overexpressed HK-2 under these stress conditions. The target gene of miRNA was identified by 3'-UTR-luciferase assay. RESULTS: We identified 8 and 10 miRNAs whose expression was significantly altered by oxidative and ER stresses, respectively. Among these, expression of miR-205 was markedly decreased in both stress conditions. Functional analysis revealed that decreased miR-205 led to an increase in cell susceptibility to oxidative and ER stresses, and that this increase was associated with the induction of intracellular ROS and suppression of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell growth or morphology, cell viability under oxidative or ER stress conditions was partially restored. Further, miR-205 bound to the 3'-UTR of the prolyl hydroxylase 1 (PHD1/EGLN2 gene and suppr