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Sample records for cell carcinoma rcc

  1. Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers.

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    Argani, Pedram; Hicks, Jessica; De Marzo, Angelo M; Albadine, Roula; Illei, Peter B; Ladanyi, Marc; Reuter, Victor E; Netto, George J

    2010-09-01

    Xp11 translocation renal cell carcinoma (RCC) harbor various TFE3 gene fusions, and are known to underexpress epithelial immunohistochemical (IHC) markers such as cytokeratin and EMA relative to usual adult type RCC; however, their profile in reference to other IHC markers that are differentially expressed in other subtypes of RCC has not been systematically assessed. Few therapeutic targets have been identified in these aggressive cancers. We created 2 tissue microarrays (TMA) containing five 1.4-mm cores from each of 21 Xp11 translocation RCC (all confirmed by TFE3 IHC, 6 further confirmed by genetics), 7 clear cell RCC (CCRCC), and 6 papillary RCC (PRCC). These TMA were labeled for a panel of IHC markers. In contrast to earlier published data, Xp11 translocation RCC frequently expressed renal transcription factors PAX8 (16/21 cases) and PAX2 (14/21 cases), whereas only 1 of 21 cases focally expressed MiTF and only 5 of 21 overexpressed p21. Although experimental data suggest otherwise, Xp11 translocation RCC did not express WT-1 (0/21 cases). Although 24% of Xp11 translocation RCC expressed HIF-1alpha (like CCRCC), unlike CCRCC CA IX expression was characteristically only focal (mean 6% cell labeling) in Xp11 translocation RCC. Other markers preferentially expressed in CCRCC or PRCC, such as HIG-2, claudin 7, and EpCAM, yielded inconsistent results in Xp11 translocation RCC. Xp11 translocation RCC infrequently expressed Ksp-cadherin (3/21 cases) and c-kit (0/21 cases), markers frequently expressed in chromophobe RCC. Using an H-score that is the product of intensity and percentage labeling, Xp11 translocation RCC expressed higher levels of phosphorylated S6, a measure of mTOR pathway activation (mean H score=88), than did CCRCC (mean H score=54) or PRCC (mean H score=44). In conclusion, in contrast to prior reports, Xp11 translocation RCC usually express PAX2 and PAX8 but do not usually express MiTF. Although they may express HIF-1alpha, they only focally

  2. Symptom burden among patients with Renal Cell Carcinoma (RCC: content for a symptom index

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    Mahadevia Parthiv J

    2007-06-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC has multiple symptoms stemming from disease and treatments. There are few validated scales for evaluating RCC symptoms. Methods A national cross-sectional study of adult RCC patients was conducted from October to December 2003 to define patient-reported RCC symptomology. Participants were asked open-ended questions regarding their signs and symptoms and completed an 86-item pilot questionnaire of physical and psychological symptoms. Patients were asked to rate the relevancy and clarity of each pilot question using a 5-point Likert scale. Subsequent open-ended caregiver interviews and a provider panel relevance ranking contributed additional information. Results The average age of the participants (n = 31 was 55 years; 55% of patients were male, 74% had attended college, and 97% were Caucasian. The five most frequent symptoms among localized-stage patients (n = 14 were irritability (79%, pain (71%, fatigue (71%, worry (71%, and sleep disturbance (64%. Among metastatic patients (n = 17, the five most frequent symptoms were fatigue (82%, weakness (65%, worry (65%, shortness of breath (53%, and irritability (53%. More than 50% of localized and metastatic-stage patients reported pain, weakness, fatigue, sleep disturbance, urinary frequency, worry, and mood disorders as being moderately to highly relevant. Conclusion A brief, self-administered RCC Symptom Index was created that captures the relevant signs and symptoms of both localized and metastatic patients. Pending additional content validation, the Index can be used to assess the signs and symptoms of RCC and the clinical benefit resulting from RCC treatment.

  3. Clinical and Pathological Complete Remission in a Patient With Metastatic Renal Cell Carcinoma (mRCC Treated With Sunitinib: Is mRCC Curable With Targeted Therapy?

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    Amishi Y. Shah

    2015-03-01

    Full Text Available We report a patient with metastatic clear-cell renal cell carcinoma (mRCC who presented with primary tumor in situ in the left kidney and metastases to bone, liver, lungs, and brain. After over 5 years of sunitinib therapy and subsequent cytoreductive left nephrectomy, the patient achieved radiographic complete response (CR and had pathologic CR in the nephrectomy specimen. Durable clinical and pathological CRs are possible with targeted agents, even with primary tumor in situ and widely disseminated metastases. Ongoing research will define the optimal duration of systemic therapy in exceptional responders and identify the molecular determinants of response and resistance.

  4. Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC

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    Freudenberg, L.S.; Goerges, R.; Stergar, H.; Bockisch, A. [Dept. of Nuclear Medicine, Univ. of Duisburg-Essen (Germany); Gauler, T.; Bauer, S. [Dept. of Internal Medicine (Cancer Research), Univ. of Duisburg-Essen (Germany); Antoch, G. [Dept. of Diagnostic and Interventional Radiology and Neuroradiology, Univ. of Duisburg-Essen (Germany); Schuette, J. [Dept. of Medical Oncology/Hematology, Marien-Hospital Duesseldorf (Germany)

    2008-07-01

    Aims: objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. Patients, methods: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48h post i.v. injection of 175-200 MBq {sup 111}In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in > 50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR {sup registered} -Depot 30mg i.m. every four weeks). Results: in 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In too patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients. Conclusions: we conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option. (orig.)

  5. Intracellular lipid in papillary renal cell carcinoma (pRCC): T2 weighted (T2W) MRI and pathologic correlation

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    Schieda, Nicola; Van der Pol, Christian B.; Moosavi, Bardia; McInnes, Matthew D.F. [The Ottawa Hospital, The University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada); Mai, Kien T.; Flood, Trevor A. [The Ottawa Hospital, The University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada)

    2015-07-15

    To evaluate if pRCCs demonstrate intracellular lipid (i-lipid) at chemical-shift (CS) MRI, and assess T2W-MRI and pathologic characteristics. Sixty-two patients with a pRCC diagnosis underwent MRI over 11 years (IRB-approved). Two radiologists independently assessed for presence of i-lipid on CS-MRI and homogeneity on T2W-MRI. Inter-observer agreement was assessed via an intraclass correlation and results were compared using the Chi-square test. Discordant cases were reviewed to establish consensus. T2W SI-ratios (SI.tumor/SI.kidney) and CS-SI index were compared using independent t-tests and Spearman correlation. Two pathologists re-evaluated the histopathology. Nine of the 62 pRCCs (14.5 %) demonstrated i-lipid; agreement was moderate (ICC = 0.63). Pathology review depicted clear cells in four tumours and foamy histiocytes in five tumours. 25.8-35.4 % (ICC = 0.65) of tumours were homogeneous on T2W-MRI. No pRCC with i-lipid was considered homogeneous (p = 0.01-0.04). Overall, T2W SI-ratio and CS-SI index were 0.89 (±0.29) and -3.63 % (-7.27 to 11.42). pRCC with i-lipid had significantly higher T2W SI-ratio (p = 0.003). There was a correlation between the CS-SI index and T2W SI-ratio, (r = 0.44, p < 0.001). Intracellular lipid is uncommonly detected in pRCCs due to clear cell changes and foamy histiocytes. These tumours are associated with heterogeneously-increased SI in T2W-MRI. (orig.)

  6. A systematic review of the efficacy and safety experience reported for sorafenib in advanced renal cell carcinoma (RCC in the post-approval setting.

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    Mayer N Fishman

    Full Text Available Sorafenib was FDA approved in 2005 for treatment of renal cell carcinoma (RCC based on the results of the pivotal phase 3 clinical trial, TARGET (Treatment Approaches in Renal Cancer Global Evaluation Trial. Since that time, numerous clinical studies have been undertaken that substantially broaden our knowledge of the use of sorafenib for this indication.We systematically reviewed PubMed, Web of Science, Embase, Cochrane Library, and www.clinicaltrials.gov for prospective clinical studies using single agent sorafenib in RCC and published since 2005. Primary endpoints of interest were progression-free survival (PFS and safety. PROSPERO International prospective register of systematic reviews #CRD42014010765.We identified 30 studies in which 2182 patients were treated with sorafenib, including 1575 patients who participated in randomized controlled phase 3 trials. In these trials, sorafenib was administered as first-, second- or third-line treatment. Heterogeneity among trial designs and reporting of data precluded statistical comparisons among trials or with TARGET. The PFS appeared shorter in second- vs. first-line treatment, consistent with the more advanced tumor status in the second-line setting. In some trials, incidences of grade 3/4 hypertension or hand-foot skin reaction (HFSR were more than double that seen in TARGET (4% and 6%, respectively. These variances may be attributable to increased recognition of HFSR, or potentially differences in dose adjustments, that could be consequences of increased familiarity with sorafenib usage. Several small studies enrolled exclusively Asian patients. These studies reported notably longer PFS than was observed in TARGET. However, no obvious corresponding differences in disease control rate and overall survival were seen.Collectively, more recent experiences using sorafenib in RCC are consistent with results reported for TARGET with no marked changes of response endpoints or new safety signals

  7. Local control rates of metastatic renal cell carcinoma to the bone using stereotactic body radiation therapy: Is RCC truly radioresistant?′

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    Bourlon, Maria T.; Bedrick, Edward; Bhatia, Shilpa; Kessler, Elizabeth R.; Flaig, Thomas W.; Fisher, Christine M.; Kavanagh, Brian D; Lam, Elaine T.; Karam, Sana D.

    2015-01-01

    Purpose We report the radiographic and clinical response rate of stereotactic body radiation therapy (SBRT) compared with conventional fractionated external beam radiation therapy (CF-EBRT) for renal cell carcinoma (RCC) bone lesions treated at our institution. Methods and materials Forty-six consecutive patients were included in the study, with 95 total lesions treated (50 SBRT, 45 CF-EBRT). We included patients who had histologic confirmation of primary RCC and radiographic evidence of metastatic bone lesions. The most common SBRT regimen used was 27 Gy in 3 fractions. Results Median follow-up was 10 months (range, 1-64 months). Median time to symptom control between SBRT and CF-EBRT were 2 (range, 0-6 weeks) and 4 weeks (range, 0-7 weeks), respectively. Symptom control rates with SBRT and CF-EBRT were significantly different (P = .020) with control rates at 10, 12, and 24 months of 74.9% versus 44.1%, 74.9% versus 39.9%, and 74.9% versus 35.7%, respectively. The median time to radiographic failure and unadjusted pain progression was 7 months in both groups. When controlling for gross tumor volume, dose per fraction, smoking, and the use of systemic therapy, biologically effective dose ≥80 Gy was significant for clinical response (hazard ratio [HR], 0.204; 95% confidence interval [CI], 0.043-0.963; P = .046) and radiographic (HR, 0.075; 95% CI, 0.013-0.430; P = .004). When controlling for gross tumor volume and total dose, biologically effective dose ≥80 Gy was again predictive of clinical local control (HR, 0.140; 95% CI, 0.025-0.787; P = .026). Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 toxicity reported. Conclusions SBRT is both safe and effective for treating RCC bone metastases, with rapid improvement in symptoms after treatment and more durable clinical and radiographic response rate. Future prospective trials are needed to further define efficacy and toxicity of treatment, especially in the setting of targeted agents

  8. RCC1-dependent activation of Ran accelerates cell cycle and DNA repair, inhibiting DNA damage-induced cell senescence.

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    Cekan, Pavol; Hasegawa, Keisuke; Pan, Yu; Tubman, Emily; Odde, David; Chen, Jin-Qiu; Herrmann, Michelle A; Kumar, Sheetal; Kalab, Petr

    2016-04-15

    The coordination of cell cycle progression with the repair of DNA damage supports the genomic integrity of dividing cells. The function of many factors involved in DNA damage response (DDR) and the cell cycle depends on their Ran GTPase-regulated nuclear-cytoplasmic transport (NCT). The loading of Ran with GTP, which is mediated by RCC1, the guanine nucleotide exchange factor for Ran, is critical for NCT activity. However, the role of RCC1 or Ran⋅GTP in promoting cell proliferation or DDR is not clear. We show that RCC1 overexpression in normal cells increased cellular Ran⋅GTP levels and accelerated the cell cycle and DNA damage repair. As a result, normal cells overexpressing RCC1 evaded DNA damage-induced cell cycle arrest and senescence, mimicking colorectal carcinoma cells with high endogenous RCC1 levels. The RCC1-induced inhibition of senescence required Ran and exportin 1 and involved the activation of importin β-dependent nuclear import of 53BP1, a large NCT cargo. Our results indicate that changes in the activity of the Ran⋅GTP-regulated NCT modulate the rate of the cell cycle and the efficiency of DNA repair. Through the essential role of RCC1 in regulation of cellular Ran⋅GTP levels and NCT, RCC1 expression enables the proliferation of cells that sustain DNA damage. PMID:26864624

  9. The value of blood oxygenation level-dependent (BOLD MR imaging in differentiation of renal solid mass and grading of renal cell carcinoma (RCC: analysis based on the largest cross-sectional area versus the entire whole tumour.

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    Guang-Yu Wu

    Full Text Available To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade.Ninety-five patients with 139 renal masses (93 malignant and 46 benign who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest and from the whole tumour (R2*whole. Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis.The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8. The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79 was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68, as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2] and R2*largest (AUC=0.75[observer1] was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p 0.7 and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1].BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross

  10. Local Control Rates of Metastatic Renal Cell Carcinoma (RCC) to Thoracic, Abdominal, and Soft Tissue Lesions Using Stereotactic Body Radiotherapy (SBRT)

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    Altoos, Basel; Amini, Arya; Yacoub, Muthanna; Bourlon, Maria T.; Kessler, Elizabeth E.; Flaig, Thomas W.; Fisher, Christine M.; Kavanagh, Brian D.; Lam, Elaine T.; Karam, Sana D.

    2015-01-01

    Background and purpose We report the radiographic response rate of SBRT compared to conventional fractionated radiotherapy (CF-EBRT) for thoracic, abdominal, skin and soft tissue RCC lesions treated at our institution. Material and methods Fifty three lesions where included in the study (36 SBRT, 17 CF-EBRT), treated from 2004 to 2014 at our institution. We included patients that had thoracic, skin & soft tissue (SST), and abdominal metastases of histologically confirmed RCC. The most common ...

  11. Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2α/C-MYC axis under hypoxia.

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    Zhai, W; Sun, Y; Jiang, M; Wang, M; Gasiewicz, T A; Zheng, J; Chang, C

    2016-09-15

    It is well established that hypoxia contributes to tumor progression in a hypoxia inducible factor-2α (HIF-2α)-dependent manner in renal cell carcinoma (RCC), yet the role of long noncoding RNAs (LncRNAs) involved in hypoxia-mediated RCC progression remains unclear. Here we demonstrate that LncRNA-SARCC (Suppressing Androgen Receptor in Renal Cell Carcinoma) is differentially regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner both in RCC cell culture and clinical specimens. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells. Mechanism dissection reveals that LncRNA-SARCC can post-transcriptionally regulate androgen receptor (AR) by physically binding and destablizing AR protein to suppress AR/HIF-2α/C-MYC signals. In return, HIF-2α can transcriptionally regulate the LncRNA-SARCC expression via binding to hypoxia-responsive elements on the promoter of LncRNA-SARCC. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2α signaling may then lead to differentially modulated RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2α/C-MYC signals against RCC progression.

  12. First Delayed Resection Findings After Irreversible Electroporation (IRE) of Human Localised Renal Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Trial

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    IntroductionIt is postulated that focal IRE affords complete ablation of soft-tissue tumours while protecting the healthy peritumoral tissue. Therefore, IRE may be an interesting option for minimally invasive, kidney-tissue-sparing, non-thermal ablation of renal tumours.AimWith this current pilot study (“IRENE trial”), we present the first detailed histopathological data of IRE of human RCC followed by delayed tumour resection. The aim of this interim analysis of the first three patients was to investigate the ablation efficiency of percutaneous image-guided focal IRE in RCC, to assess whether a complete ablation of T1a RCC and tissue preservation with the NanoKnife system is possible and to decide whether the ablation parameters need to be altered.MethodsFollowing resection 4 weeks after percutaneous IRE, the success of ablation and detailed histopathological description were used to check the ablation parameters.ResultsThe IRE led to a high degree of damage to the renal tumours (1 central, 2 peripheral; size range 15–17 mm). The postulated homogeneous, isomorphic damage was only partly confirmed. We found a zonal structuring of the ablation zone, negative margins and, enclosed within the ablation zone, very small tumour residues of unclear malignancy.ConclusionAccording to these initial, preliminary study results of the first three renal cases, a new zonal distribution of IRE damage was described and the curative intended, renal saving focal ablation of localised RCC below <3 cm by percutaneous IRE by the NanoKnife system appears to be possible, but needs further, systematic evaluation for this treatment method and treatment protocol

  13. First Delayed Resection Findings After Irreversible Electroporation (IRE) of Human Localised Renal Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Trial

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    Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Ricke, Jens, E-mail: jens.Ricke@med.ovgu.de; Pech, Maciej, E-mail: macej.pech@med.ovgu.de; Fischbach, Frank, E-mail: frank.fischbach@med.ovgu.de; Jürgens, Julian, E-mail: julian.juergens@med.ovgu.de [University of Magdeburg, Department of Radiology (Germany); Siedentopf, Sandra, E-mail: sandra.siedentopf@med.ovgu.de; Roessner, Albert, E-mail: albert.roessner@med.ovgu.de [University of Magdeburg, Institute of Pathology (Germany); Porsch, Markus, E-mail: markus.porsch@med.ovgu.de; Baumunk, Daniel, E-mail: daniel.baumunk@med.ovgu.de; Schostak, Martin, E-mail: martin.schostak@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Köllermann, Jens, E-mail: jens.koellermann@sana.de [Sana Klinikum Offenbach Am Main, Institute of Pathology (Germany); Liehr, Uwe-Bernd, E-mail: uwe-bernd.liehr@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany)

    2016-02-15

    IntroductionIt is postulated that focal IRE affords complete ablation of soft-tissue tumours while protecting the healthy peritumoral tissue. Therefore, IRE may be an interesting option for minimally invasive, kidney-tissue-sparing, non-thermal ablation of renal tumours.AimWith this current pilot study (“IRENE trial”), we present the first detailed histopathological data of IRE of human RCC followed by delayed tumour resection. The aim of this interim analysis of the first three patients was to investigate the ablation efficiency of percutaneous image-guided focal IRE in RCC, to assess whether a complete ablation of T1a RCC and tissue preservation with the NanoKnife system is possible and to decide whether the ablation parameters need to be altered.MethodsFollowing resection 4 weeks after percutaneous IRE, the success of ablation and detailed histopathological description were used to check the ablation parameters.ResultsThe IRE led to a high degree of damage to the renal tumours (1 central, 2 peripheral; size range 15–17 mm). The postulated homogeneous, isomorphic damage was only partly confirmed. We found a zonal structuring of the ablation zone, negative margins and, enclosed within the ablation zone, very small tumour residues of unclear malignancy.ConclusionAccording to these initial, preliminary study results of the first three renal cases, a new zonal distribution of IRE damage was described and the curative intended, renal saving focal ablation of localised RCC below <3 cm by percutaneous IRE by the NanoKnife system appears to be possible, but needs further, systematic evaluation for this treatment method and treatment protocol.

  14. Dynamic contrast-enhanced CT (DCE-CT) as a potential biomarker in patients with metastatic renal cell carcinoma (mRCC)

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    Mains, Jill Rachel; Donskov, Frede; Pedersen, Erik Morre;

    slope method) was performed blinded to treatment group. DCE-CT scans were performed using a Philips iCT or Brilliance 64 at baseline, 5 and 10 weeks and 6, 9, 12, 15, 18, 21 and 24 months. Perfusion (P, ml/min/100 ml), peak enhancement (PE, HU), time to peak (TTP, sec) and blood volume (BV, ml/100 g......Purpose To explore the impact of DCE-CT as a biomarker in mRCC.  Methods and Materials 12 patients with mRCC participating in a phase II trial with immunotherapy and bevacizumab and with a follow-up time of at least 2 years were included in this preliminary analysis. DCE-CT interpretation (max......) were calculated using a Philips Extended Brilliance workstation version 4.5.2. DCE-CT parameters were correlated with the relative changes in the sums of diameters (RECIST 1.1), progression free survival (PFS) and overall survival (OS) using Wilcoxon, Man-Whitney, Kaplan Meier and Log Rank statistics...

  15. Nuclear EGFR characterize still controlled proliferation retained in better differentiated clear cell RCC.

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    Ahel, J; Dordevic, G; Markic, D; Mozetic, V; Spanjol, J; Grahovac, B; Stifter, S

    2015-08-01

    Renal cell carcinoma (RCC) is the most common solid kidney tumor representing 2-3% of all cancers, with the highest frequency occurring in Western countries. There was a worldwide and European annual increase in incidence of approximately 2% although incidence has been stabilized in last few years. One third of the patients already have metastases in the time of the diagnosis with poor prognosis because RCC are radio and chemoresistant. The prognostic value of EGFR over-expression in RCC is a controversial issue that could be explained by different histological types of study tumors and non-standardized criteria for evaluation of expression. Recent evidences points to a new mode of EGFR signaling pathway in which activated EGFR undergoes nuclear translocalization and then, as transcription factor, mediates gene expression and other cellular events required for highly proliferating activities. According to our observations, the membranous expression of EGFR associates with high nuclear grade and poor differentiated tumors. On the other hand, nuclear EGFR expression was high in low nuclear graded and well differentiated tumors with good prognosis. We hypothesize that this mode of EGFR signaling characterizes still controlled proliferation retained in well differentiated RCC with Furhman nuclear grade I or II.

  16. Study of the role of SETD2 mutations in clear cell renal cell carninoma (ccRCC)

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    Almeida, Catarina Faria de

    2013-01-01

    Trabalho de projecto de mestrado em Bioestatística, apresentado à Universidade de Lisboa, através da Faculdade de Ciências, 2013 Clear cell Renal Cell Carcinoma, ccRCC, is the most common form of Renal Cancer, accounting for 90% of these cancers cases. It is well established that the majority of these cancers happen when both alleles of VHL (Von Hippel Lindau) tumour suppressor gene are mutated. It has also been observed that patients with this form of cancer present mutations on the SETD2...

  17. Translocation Renal Cell Carcinomas in Adults: A Single Institution Experience

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    Zhong, Minghao; De Angelo, Patricia; Osborne, Lisa; Mondolfi, Paniz; Geller, Matthew; Yang, Youfeng; Linehan, W. Marston; Merino, Maria J.; Cordon-Cardo, Carlos; Cai, Dongming

    2012-01-01

    Translocation renal cell carcinoma is a newly recognized subtype of renal cell carcinoma (RCC) with chromosomal translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21). Xp11 translocation RCC was originally described as a pediatric neoplasm representing 20–40% of pediatric RCCs with a much lower frequency in the adult population. TFEB translocation RCC is very rare, with approximately 10 cases reported in the literature. Here, we describe the clinicopathological features of ad...

  18. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma

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    SHINMURA, KAZUYA; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-01-01

    Abstract Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequ...

  19. Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

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    Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L

    2015-01-01

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes ob...

  20. Morphologic, Molecular, and Taxonomic Evolution of Renal Cell Carcinoma: A Conceptual Perspective With Emphasis on Updates to the 2016 World Health Organization Classification.

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    Udager, Aaron M; Mehra, Rohit

    2016-10-01

    Molecular and morphologic interrogation has driven a much-needed reexamination of renal cell carcinoma (RCC). Indeed, the recently released 2016 World Health Organization classification now recognizes 12 distinct RCC subtypes, as well as several other emerging/provisional RCC entities. From a clinical perspective, accurate RCC classification may have important implications for patients and their families, including prognostic risk stratification, targeted therapeutics selection, and identification for genetic testing. In this review, we provide a conceptual framework for approaching RCC diagnosis and classification by categorizing RCCs as tumors with clear cytoplasm, papillary architecture, and eosinophilic (oncocytic) cytoplasm. The currently recognized 2016 World Health Organization classification for RCC subtypes is briefly discussed, including new diagnostic entities (clear cell papillary RCC, hereditary leiomyomatosis and RCC-associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, and acquired cystic disease-associated RCC) and areas of evolving RCC classification, such as transcription elongation factor B subunit 1 (TCEB1)-mutated RCC/RCC with angioleiomyoma-like stroma/RCC with leiomyomatous stroma, RCC associated with anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangement, thyroidlike follicular RCC, and RCC in neuroblastoma survivors. For each RCC subtype, relevant clinical, molecular, gross, and microscopic findings are reviewed, and ancillary studies helpful for its differential diagnosis are presented, providing a practical approach to modern RCC classification. PMID:27684973

  1. Xp11 translocation renal cell carcinoma morphologically mimicking clear cell-papillary renal cell carcinoma in an adult patient: report of a case expanding the morphologic spectrum of Xp11 translocation renal cell carcinomas.

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    Parihar, Asmita; Tickoo, Satish K; Kumar, Sunil; Arora, Vinod Kumar

    2015-05-01

    Xp11 translocation renal cell carcinoma (RCC) is a relatively rare tumor mainly affecting children and adolescents. It shows significant morphological overlap with the 2 most common adult renal tumors, which are the clear cell (conventional) RCC and papillary RCC. We describe case of a young adult female who presented with right flank pain and abdominal mass. Radiological investigations showed features suggestive of renal cell carcinoma in the right kidney. Histopathological findings while suggestive of Xp11 carcinoma, showed significant overlap with the recently described entity clear cell papillary RCC. TFE3 immunohistochemistry confirmed the tumor to be Xp11 translocation RCC. The patient had an aggressive course with lymph node metastasis. In this report, we discuss differential diagnosis and the diagnostic challenges of Xp11 translocation RCC in adults.

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

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    Michael Kongnyuy

    2015-01-01

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

  3. Renal cell carcinoma: links and risks

    Science.gov (United States)

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  4. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-01-01

    Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC) and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested. PMID:21577373

  5. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tarun Rustagi

    2011-04-01

    Full Text Available Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested.

  6. 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.

  7. Duodenal bleeding from metastatic renal cell carcinoma.

    Science.gov (United States)

    Rustagi, Tarun; Rangasamy, Priya; Versland, Mark

    2011-04-20

    Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC) and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested.

  8. Renal cell carcinoma: links and risks.

    Science.gov (United States)

    Kabaria, Reena; Klaassen, Zachary; Terris, Martha K

    2016-01-01

    This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. PMID:27022296

  9. Renal Preservation Therapy for Renal Cell Carcinoma

    OpenAIRE

    Yichun Chiu; Allen W. Chiu

    2012-01-01

    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...

  10. Targeted therapy for metastatic renal cell carcinoma

    OpenAIRE

    Patel, P H; Chaganti, R.S.K.; Motzer, R J

    2006-01-01

    Metastatic renal cell carcinoma (RCC) has historically been refractory to cytotoxic and hormonal agents; only interleukin 2 and interferon alpha provide response in a minority of patients. We reviewed RCC biology and explored the ways in which this understanding led to development of novel, effective targeted therapies. Small molecule tyrosine kinase inhibitors, monoclonal antibodies and novel agents are all being studied, and phase II studies show promising activity of sunitinib, sorafenib a...

  11. Systemic adjuvant therapies in renal cell carcinoma

    OpenAIRE

    Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...

  12. 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.

  13. Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Monika Vyas

    2013-01-01

    Full Text Available Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.

  14. 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.

  15. Tubulocystic renal cell carcinoma: a new radiological entity

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

  16. Molecular Genetic Alterations in Renal Cell Carcinomas With Tubulocystic Pattern: Tubulocystic Renal Cell Carcinoma, Tubulocystic Renal Cell Carcinoma With Heterogenous Component and Familial Leiomyomatosis-associated Renal Cell Carcinoma. Clinicopathologic and Molecular Genetic Analysis of 15 Cases.

    Science.gov (United States)

    Ulamec, Monika; Skenderi, Faruk; Zhou, Ming; Krušlin, Božo; Martínek, Petr; Grossmann, Petr; Peckova, Kvetoslava; Alvarado-Cabrero, Isabel; Kalusova, Kristyna; Kokoskova, Bohuslava; Rotterova, Pavla; Hora, Milan; Daum, Ondrej; Dubova, Magdalena; Bauleth, Kevin; Slouka, David; Sperga, Maris; Davidson, Whitney; Rychly, Boris; Perez Montiel, Delia; Michal, Michal; Hes, Ondrej

    2016-08-01

    The characteristic morphologic spectrum of tubulocystic renal cell carcinoma (TC-RCC) may include areas resembling papillary RCC (PRCC). Our study includes 15 RCCs with tubulocystic pattern: 6 TC-RCCs, 1 RCC-high grade with tubulocystic architecture, 5 TC-RCCs with foci of PRCC, 2 with high-grade RCC (HGRCC) not otherwise specified, and 1 with a clear cell papillary RCC/renal angiomyoadenomatous tumor-like component. We analyzed aberrations of chromosomes 7, 17, and Y; mutations of VHL and FH genes; and loss of heterozygosity at chromosome 3p. Genetic analysis was performed separately in areas of classic TC-RCC and in those with other histologic patterns. The TC-RCC component demonstrated disomy of chromosome 7 in 9/15 cases, polysomy of chromosome 17 in 7/15 cases, and loss of Y in 1 case. In the PRCC component, 2/3 analyzable cases showed disomy of chromosome 7 and polysomy of chromosome 17 with normal Y. One case with focal HGRCC exhibited only disomy 7, whereas the case with clear cell papillary RCC/renal angiomyoadenomatous tumor-like pattern showed polysomies of 7 and 17, mutation of VHL, and loss of heterozygosity 3p. FH gene mutation was identified in a single case with an aggressive clinical course and predominant TC-RCC pattern. The following conclusions were drawn: (1) TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. (2) The biological nature of PRCC/HGRCC-like areas within TC-RCC remains unclear. Our data suggest that heterogenous TC-RCCs may be associated with an adverse clinical outcome. (3) Hereditary leiomyomatosis-associated RCC can be morphologically indistinguishable from "high-grade" TC-RCC; therefore, in TC-RCC with high-grade features FH gene status should be tested. PMID:26447894

  17. Treatment of elderly patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Zanardi, Elisa; Grassi, Paolo; Cavo, Alessia; Verzoni, Elena; Maggi, Claudia; De Braud, Filippo; Boccardo, Francesco; Procopio, Giuseppe

    2016-01-01

    The risk of developing renal cell carcinoma (RCC) increases with age, and given the constant gain in life expectancy of the general population, both localized RCC and metastatic RCC (mRCC) are more frequently observed in the elderly population. The elderly are a heterogeneous group of patients often characterized by the presence of comorbidities, different compliance to treatment and polypharmacy. Here we review the available data with the aim to analyze the safety and efficacy of new targeted therapies (TTs) in elderly mRCC patients. TTs seem to be effective in both older and younger patients, but elderly patients appear to show reduced tolerance to treatments compared to younger patients. Prospective trials are needed to better understand how to manage mRCC in elderly patients. PMID:26654225

  18. Multifocal renal cell carcinoma of different histological subtypes in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Na, Ki Yong; Kim, Hyun-Soo; Park, Yong-Koo; Chang, Sung-Goo; Kim, Youn Wha

    2012-08-01

    Renal cell carcinoma (RCC) in autosomal dominant polycystic kidney (ADPKD) is rare. To date, 54 cases of RCC in ADPKD have been reported. Among these, only 2 cases have different histologic types of RCC. Here we describe a 45-year-old man who received radical nephrectomy for multifocal RCC with synchronous papillary and clear cell histology in ADPKD and chronic renal failure under regular hemodialysis. The case reported herein is another example of the rare pathological finding of RCC arising in a patient with ADPKD.

  19. Unusual gastric and pancreatic metastatic renal cell carcinoma presentation 10 years after surgery and immunotherapy: A case report and a review of literature

    Institute of Scientific and Technical Information of China (English)

    Chiara Riviello; Ilaria Tanini; Greta Cipriani; Pietro Pantaleo; Carlo Nozzoli; Alberto Poma; Viligiardi Riccardo; Andrea Valeri

    2006-01-01

    Renal cell carcinoma (RCC) is the most common renal tumor, accounting for 2% -3% of all malignancies.Though RCC is known to spread hematogenously, isolated RCC metastasis to the stomach is a rare event. In this article, we describe the clinical course of a patient who developed a pancreatic recurrence of RCC and 1 year later a gastric recurrence of RCC treated 10 years ago with a resection and interleukin-2 (IL-2).Accumulating evidence indicates that metastatic involvement of the pancreas and stomach should be suspected in any patient with a history of RCC who presents with gastrointestinal symptoms even 10 years after RCC resection and immunotherapy.

  20. [Outlook: Future therapy of renal cell carcinoma].

    Science.gov (United States)

    Bergmann, Lothar; Miller, Kurt

    2010-01-01

    Targeted therapies have fundamentally altered the therapy of metastatic renal cell carcinoma (mRCC). Sunitinib today is an internationally recommended reference standard in first-line therapy; other drugs such as Temsirolimus, Everolimus, Bevacizumab (in combination with Interferon-alpha) and Sorafenib are part of the therapeutic arsenal. Practitioners thus have now more and better therapeutic options at hand, leading to a significantly improved prognosis for mRCC patients. Numerous ongoing research activities aim at the improvement of the benefits of the new compounds in the metastatic situation or application earlier in the course of the disease. Key aspects of future development in RCC are the optimization of the current therapy options by developing new targeted therapies, the search for the best combinations and sequences including the role of nephrectomy and the assessment in the adjuvant or neo-adjuvant setting. The following contribution provides an overview of ongoing studies, thus giving insight into the future therapy of RCC. PMID:20164673

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

    OpenAIRE

    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 inf...

  2. Racial difference in histologic subtype of renal cell carcinoma

    International Nuclear Information System (INIS)

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

  3. The epidemiology of renal cell carcinoma

    NARCIS (Netherlands)

    Ljungberg, B.; Campbell, S.C.; Cho, H.Y.; Jacqmin, D.; Lee, J.E.; Weikert, S.; Kiemeney, L.A.L.M.

    2011-01-01

    CONTEXT: Kidney cancer is among the 10 most frequently occurring cancers in Western communities. Globally, about 270 000 cases of kidney cancer are diagnosed yearly and 116 000 people die from the disease. Approximately 90% of all kidney cancers are renal cell carcinomas (RCC). OBJECTIVE: The causes

  4. The Nephrologist's Tumor: Basic Biology and Management of Renal Cell Carcinoma.

    Science.gov (United States)

    Hu, Susie L; Chang, Anthony; Perazella, Mark A; Okusa, Mark D; Jaimes, Edgar A; Weiss, Robert H

    2016-08-01

    Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel-Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist's tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist's tumor.

  5. Renal cell carcinoma with rhabdoid-like features lack intracytoplasmic inclusion bodies and show aggressive behavior.

    Science.gov (United States)

    Sugimoto, Masaaki; Kohashi, Kenichi; Kuroiwa, Kentaro; Abe, Tatsuro; Yamada, Yuichi; Shiota, Masaki; Imada, Kenjiro; Naito, Seiji; Oda, Yoshinao

    2016-03-01

    In renal cell carcinoma (RCC), tumor cells with rhabdoid features are characterized by eccentric nuclei, prominent nucleoli, and eosinophilic cytoplasm with intracytoplasmic inclusion bodies. In RCC, tumor cells have also been observed resembling rhabdomyoblasts or rhabdoid but without intracytoplasmic inclusion bodies, and here, we defined these rhabdoid-like features of these cells. To this end, we studied a series of clear cell RCC (ccRCC) with rhabdoid features and compared them with a series of ccRCC with rhabdoid-like features to clarify the differences in the immunohistochemical profile and biological behavior. From 695 cases of ccRCC (80.8 % of all RCCs), 18 cases with rhabdoid features (2.1 % of all RCCs) and 25 cases with rhabdoid-like features (2.9 % of all RCCs) were investigated. The 5-year survival rate for ccRCC with rhabdoid features was 44.7 % and for ccRCC with rhabdoid-like features 30.3 %. Although ccRCC with rhabdoid features showed immunohistochemical co-expression of epithelial markers and vimentin as seen in malignant rhabdoid tumors, ccRCC with rhabdoid-like features showed no such co-expression. Multivariate analyses of cancer-specific survival revealed that perinephric tissues invasion was an independent prognostic factor in ccRCC with rhabdoid features (p = 0.0253) but not in ccRCC with rhabdoid-like features. In summary, although their prognosis is similar, the marker profile and pattern of extension of ccRCC with rhabdoid-like is different from that of ccRCC with rhabdoid features. Therefore, ccRCC with rhabdoid-like features should be distinguished from ccRCC with rhabdoid features.

  6. 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...... of sRCC is needed to develop alternative therapeutics....

  7. Renal cell carcinoma: links and risks

    Directory of Open Access Journals (Sweden)

    Kabaria R

    2016-03-01

    Full Text Available Reena Kabaria, Zachary Klaassen, Martha K Terris Department of Surgery, Section of Urology, Augusta University, Augusta, GA, USA Abstract: This review provides an overview of the incidence of renal cell carcinoma (RCC and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses. The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect. Keywords: renal cell carcinoma, risk factors, incidence, smoking, obesity, hypertension

  8. A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

    NARCIS (Netherlands)

    Wu, Xifeng; Scelo, Ghislaine; Purdue, Mark P.; Rothman, Nathaniel; Johansson, Mattias; Ye, Yuanqing; Wang, Zhaoming; Zelenika, Diana; Moore, Lee E.; Wood, Christopher G.; Prokhortchouk, Egor; Gaborieau, Valerie; Jacobs, Kevin B.; Chow, Wong-Ho; Toro, Jorge R.; Zaridze, David; Lin, Jie; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Jinga, Viorel; Bencko, Vladimir; Slamova, Alena; Holcatova, Ivana; Navratilova, Marie; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S.; Davis, Faith G.; Schwartz, Kendra L.; Banks, Rosamonde E.; Selby, Peter J.; Harnden, Patricia; Berg, Christine D.; Hsing, Ann W.; Grubb, Robert L.; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J.; Ramon Quiros, Jose; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Allen, Naomi E.; Bueno-de-Mesquita, H. Bas; Peeters, Petra H. M.; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Borje; Overvad, Kim; Tjonneland, Anne; Romieu, Isabelle; Riboli, Elio; Stevens, Victoria L.; Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan M.; Pharoah, Paul D.; Easton, Douglas F.; Albanes, Demetrius; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Fletcher, Tony; Koppova, Kvetoslava; Cussenot, Olivier; Cancel-Tassin, Geraldine; Benhamou, Simone; Hildebrandt, Michelle A.; Pu, Xia; Foglio, Mario; Lechner, Doris; Hutchinson, Amy; Yeager, Meredith; Fraumeni, Joseph F.; Lathrop, Mark; Skryabin, Konstantin G.; McKay, James D.; Gu, Jian; Brennan, Paul; Chanock, Stephen J.

    2012-01-01

    Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome- wide association study (GWAS). We analyzed 533 191 single nucleotide poly

  9. Translocation Renal Cell Carcinoma t(6;11)(p21;q12) and Sickle Cell Anemia: First Report and Review of the Literature.

    Science.gov (United States)

    Chaste, Damien; Vian, Emmanuel; Verhoest, Gregory; Blanchet, Pascal

    2014-02-01

    Translocation renal cell carcinoma (RCC) is a family of rare tumors recently identified in the pediatric and young adult population. We report the first case of a young woman from French West Indies with sickle cell anemia who developed a translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition are known to develop renal medullary carcinoma (RMC). To our knowledge, this is the first case described in the literature of a translocation RCC associated with sickle cell disease. Here we discuss the relation between translocation RCC, RMC, and sickle cell disease.

  10. Single metastatic renal cell carcinoma in gallbladder: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Young; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Yi, Kyung Sik; Park, Kil Sun; Sung, Ro Hyun [Chungbuk National Univ. Hospital, Cheongju (Korea, Republic of)

    2012-07-15

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancy. 25% to 57% of RCC patients exhibit overt evidence of metastatic disease at initial presentation. Metastases to the gallbladder is uncommon and usually detected in only 0.4-0.6% of autopsies. We report the case of a 58 year old man who presented with a metastasis in the gallbladder from RCC. He had undergone went a right nephrectomy four years ago. There was no evidence of metastasis. A follow up abdomen CT scan taken three years after operation showed a polypoid lesion within the gallbladder. The size of the polypoid lesion had increased at the follow up CT and the enhancement pattern of lesion became similar to that of RCC. A Cholecystectomy was performed. Histopathological examination revealed the polyp was clear cell carcinoma of metastatic origin from kidney.

  11. A case of renal cell carcinoma with an extensive inferior vena cava thrombosis

    Directory of Open Access Journals (Sweden)

    Majd Alfreijat

    2016-10-01

    Full Text Available Renal cell carcinoma (RCC is the most prevalent primary renal malignant neoplasm in adults. Most of the cases are usually found incidentally. It is commonly associated with venous thrombosis. We demonstrate a case of a RCC which was associated with an extensive thrombus that reached the upper part of the inferior vena cava (IVC. We also perform a brief literature review about the association between RCC and IVC thrombosis.

  12. Gonadal vein tumor thrombosis due to renal cell carcinoma.

    Science.gov (United States)

    Haghighatkhah, Hamidreza; Karimi, Mohammad Ali; Taheri, Morteza Sanei

    2015-01-01

    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.

  13. Colon metastasis of chromophobe renal cell carcinoma with sarcomatoid change

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wei-ping; YU Yan-lan; CHEN Zhi-qiang; HUANG Xue-feng; ZHANG Zhi-gen

    2012-01-01

    We present a rare case of colonic metastasis of renal cell carcinoma (RCC) and review the literature.A 54-year-old male was referred to our hospital with a history of bloody stools and fever.A dght kidney tumor measuring about 10 cm in diameter was found by abdominal computed tomography.Right radical nephrectomy and a right hemicolectomy with ileotransversostomy were performed.Pathological diagnosis was chromophobe RCC with sarcomotoid change involving the colon.Chromophobe RCC with sarcomotoid change is very rare.

  14. Robot-Assisted Retroperitoneoscopic Surgery for Synchronous Contralateral Ureteral Metastasis of Renal-Cell Carcinoma

    Science.gov (United States)

    Lai, Wei-Hong; Chiu, Allen Wen-Shien; Lu, Chih-Cheng; Huang, Steven Kuan-Hua

    2015-01-01

    Abstract Renal-cell carcinoma (RCC) with synchronous metastasis to contralateral ureter is extremely rare with only four cases reported in the literature. We report a case of synchronous metastatic RCC to the contralateral ureter with effective robot-assisted retroperitoneoscopic nephron-sparing surgery that leads to favorable oncologic and functional outcome.

  15. Better survival of renal cell carcinoma in patients with inflammatory bowel disease

    NARCIS (Netherlands)

    Derikx, L.A.A.P.; Nissen, L.H.C.; Drenth, J.P.H.; Herpen, C.M.L. van; Kievit, W.; Verhoeven, R.H.; Mulders, P.F.A.; Kaa, C.A. van de; Boers-Sonderen, M.J.; Heuvel, T.R. van den; Pierik, M.; Nagtegaal, I.D.; Hoentjen, F.

    2015-01-01

    BACKGROUND: Immunosuppressive therapy may impact cancer risk in inflammatory bowel disease (IBD). Cancer specific data regarding risk and outcome are scarce and data for renal cell carcinoma (RCC) are lacking. We aimed(1) to identify risk factors for RCC development in IBD patients (2) to compare RC

  16. The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells

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    Sanderson Helen S

    2010-06-01

    Full Text Available Abstract Background Regulator of chromosome condensation 1 (RCC1 is the guanine nucleotide exchange factor for Ran GTPase. Localised generation of Ran-GTP by RCC1 on chromatin is critical for nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Both the N-terminal tail of RCC1 and its association with Ran are important for its interaction with chromatin in cells. In vitro, the association of Ran with RCC1 induces a conformational change in the N-terminal tail that promotes its interaction with DNA. Results We have investigated the mechanism of the dynamic interaction of the α isoform of human RCC1 (RCC1α with chromatin in live cells using fluorescence recovery after photobleaching (FRAP of green fluorescent protein (GFP fusions. We show that the N-terminal tail stabilises the interaction of RCC1α with chromatin and this function can be partially replaced by another lysine-rich nuclear localisation signal. Removal of the tail prevents the interaction of RCC1α with chromatin from being stabilised by RanT24N, a mutant that binds stably to RCC1α. The interaction of RCC1α with chromatin is destabilised by mutation of lysine 4 (K4Q, which abolishes α-N-terminal methylation, and this interaction is no longer stabilised by RanT24N. However, α-N-terminal methylation of RCC1α is not regulated by the binding of RanT24N. Conversely, the association of Ran with precipitated RCC1α does not require the N-terminal tail of RCC1α or its methylation. The mobility of RCC1α on chromatin is increased by mutation of aspartate 182 (D182A, which inhibits guanine-nucleotide exchange activity, but RCC1αD182A can still bind nucleotide-free Ran and its interaction with chromatin is stabilised by RanT24N. Conclusions These results show that the stabilisation of the dynamic interaction of RCC1α with chromatin by Ran in live cells requires the N-terminal tail of RCC1α. α-N-methylation is not regulated by formation of the binary

  17. Gene expression profile of renal cell carcinoma clear cell type

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    Marcos F. Dall’Oglio

    2010-08-01

    Full Text Available PURPOSE: The determination of prognosis in patients with renal cell carcinoma (RCC is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT. MATERIALS AND METHODS: We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1 low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2 high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3 metastatic RCC-CCT. Normal renal tissue was used as control. RESULTS: After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. CONCLUSION: These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.

  18. 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.

  19. Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is a common urological cancer with a poor prognosis. A recent cohort study revealed that the median survival of RCC patients was only 1.5 years and that <10% of the patients in the study survived up to 5 years. In tumor development, Rab GTPase are known to play potential roles such as regulation of cell proliferation, migration, invasion, communication, and drug resistance in multiple tumors. However, the correlation between Rabs expression and the occurrence, development, and metastasis of RCC remains unclear. In this study, we analyzed the transcriptional levels of 52 Rab GTPases in RCC patients. Our results showed that high levels of Rab25 expression were significantly correlated with RCC invasion classification (P < 0.01), lymph-node metastasis (P < 0.001), and pathological stage (P < 0.01). Conversely, in 786-O and A-498 cells, knocking down Rab25 protein expression inhibited cell proliferation, migration, and invasion. Our results also demonstrated that Rab25 is a target gene of let-7d, and further suggested that Rab25 upregulation in RCC is due to diminished expression of let-7d. These findings indicate that Rab25 might be a novel candidate molecule involved in RCC development, thus identifying a potential biological therapeutic target for RCC. - Highlights: • The transcriptional levels of 52 Rab GTPases were analyzed in renal cell carcinoma (RCC). • High levels of Rab25 expression were significantly correlated with clinicopathological factors of RCC. • Knockdown of Rab25 protein expression reduced RCC cells proliferation, migration, and invasion. • Rab25 is a target gene of let-7d in RCC

  20. Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuanyuan; Jia, Qingzhu [Biomedical Analysis Center, Third Military Medical University, Chongqing (China); Chongqing Key Laboratory of Cytomics, Chongqing (China); Zhang, Qian [Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing (China); Wan, Ying, E-mail: wanying_cn@163.com [Biomedical Analysis Center, Third Military Medical University, Chongqing (China); Chongqing Key Laboratory of Cytomics, Chongqing (China)

    2015-03-20

    Renal cell carcinoma (RCC) is a common urological cancer with a poor prognosis. A recent cohort study revealed that the median survival of RCC patients was only 1.5 years and that <10% of the patients in the study survived up to 5 years. In tumor development, Rab GTPase are known to play potential roles such as regulation of cell proliferation, migration, invasion, communication, and drug resistance in multiple tumors. However, the correlation between Rabs expression and the occurrence, development, and metastasis of RCC remains unclear. In this study, we analyzed the transcriptional levels of 52 Rab GTPases in RCC patients. Our results showed that high levels of Rab25 expression were significantly correlated with RCC invasion classification (P < 0.01), lymph-node metastasis (P < 0.001), and pathological stage (P < 0.01). Conversely, in 786-O and A-498 cells, knocking down Rab25 protein expression inhibited cell proliferation, migration, and invasion. Our results also demonstrated that Rab25 is a target gene of let-7d, and further suggested that Rab25 upregulation in RCC is due to diminished expression of let-7d. These findings indicate that Rab25 might be a novel candidate molecule involved in RCC development, thus identifying a potential biological therapeutic target for RCC. - Highlights: • The transcriptional levels of 52 Rab GTPases were analyzed in renal cell carcinoma (RCC). • High levels of Rab25 expression were significantly correlated with clinicopathological factors of RCC. • Knockdown of Rab25 protein expression reduced RCC cells proliferation, migration, and invasion. • Rab25 is a target gene of let-7d in RCC.

  1. Palliative Radiation Therapy for Symptomatic Control of Inoperable Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anatoly Nikolaev

    2016-01-01

    Full Text Available Renal cell carcinoma (RCC is traditionally considered to be resistant to conventional low dose radiation therapy (RT. The emergence of image-guided stereotactic body radiation therapy (SBRT made it possible to deliver much higher doses of radiation. Recent clinical trials of SBRT for RCC showed improvement in local control rates and acceptable toxicity. Here we report a case of inoperable symptomatic RCC that was managed with SBRT. Strikingly, the presenting symptoms of gross hematuria and severe anemia were completely resolved following a course of SBRT. Thus, our case report highlights the potential benefit of this technique for patients with inoperable RCC.

  2. Multiple metastatic deposits in the head and neck region from a renal cell carcinoma.

    Science.gov (United States)

    Ishak, Azlan Iskandar; Md Pauzi, Suria Hayati; Masir, Noraidah; Goh, Bee See

    2010-10-01

    Metastatic renal cell carcinoma (RCC) presenting with multiple deposits in the head and neck region is unusual. It is not uncommon for a RCC to metastasise to a distant site after years of a tumour-free period, but most of it would be expected to have a single site of deposit. We report a rare case of a patient who had a nephrectomy 10 years earlier for RCC and presented with tumours in the frontal sinus and posterior pharyngeal wall. Radiological imaging and histology confirmed metastatic RCC at both sites. PMID:22135565

  3. Mucinous Tubular and Spindle Cell Carcinoma of Kidney and Problems in Diagnosis

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    Banu SARSIK

    2011-05-01

    Full Text Available Objective: Mucinous tubular and spindle cell carcinomas (MTSCC's are recently described rare type of renal cell carcinoma (RCC. MTSCC's are characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. They have morphological similarities to papillary RCC (papRCC. We evaluated the importance of the immunohistochemical features in the differential diagnosis of MTSCC and papRCC.Material and Method: We re-evaluated 9 cases of MTSCC diagnosed between 2004 and 2010 and compared 10 cases of papRCC. All tumors were stained with alpha-methylacyl-CoA racemase (AMACR, cytokeratin 7 (CK7, CK19, renal cell carcinoma marker (RCC Ma, CD10 and kidney specific cadherin (KspCad.Results: A total of 6/9 cases were considered classical. Two of 9 MTSCC's were classified as “mucin-poor”. Foamy macrophages were identified in 4 cases. The immunoreactivity in MTSCC was AMACR 100%, CK7 100%, CK19 100%, RCC Ma 50%, CD10 11%, and KspCad 38% while the values for papRCC were AMACR 100%, CK7 90%, CK19 100%, RCC Ma 100%, CD10 80%, and KspCad 0%.Conclusion: MTSCCs may include little mucin and show a marked predominance of either of its principal morphological components. They may mimic other forms of RCC. Pathologists should be aware of the histological spectrum of MTSCCs to ensure an accurate diagnosis. Careful attention to the presence of a spindle cell population may be helpful in the differential diagnosis in tumors with predominant compact tubular growth. Immunohistochemical stains for papRCC are also expressed in MTSCC, but strong CD10 expression may not favor MTSCC.

  4. Basal Cell Carcinoma (BCC)

    Science.gov (United States)

    ... epithelioma, is the most common form of skin cancer. Basal cell carcinoma usually occurs on sun-damaged skin, especially ... other health issues. Infiltrating or morpheaform basal cell carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive ...

  5. Reduced expression of Slit2 in renal cell carcinoma.

    Science.gov (United States)

    Ma, Wei-Jie; Zhou, Yu; Lu, Dan; Dong, Dong; Tian, Xiao-Jun; Wen, Jie-Xi; Zhang, Jun

    2014-01-01

    Slit2, initially identified as an important axon guidance molecule in the nervous system, was suggested to be involved in multiple cellular processes. Recently, Slit2 was reported to function as a potential tumor suppressor in diverse tumors. In this study, we systematically analyzed the expression level of Slit2 in renal cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2 mRNA and protein expression were significantly down-regulated in renal cell carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation dramatically induced Slit2 expression in cancer cell lines with weak expression of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation was observed in 8 out of 38 patients (21.1 %), which was well correlated with the down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor suppressor in RCC, which is down-regulated in RCC partially due to promoter methylation.

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

    Science.gov (United States)

    Ciccarese, Chiara; Brunelli, Matteo; Montironi, Rodolfo; Fiorentino, Michelangelo; Iacovelli, Roberto; Heng, Daniel; Tortora, Giampaolo; Massari, Francesco

    2016-09-01

    The therapeutic landscape of renal cell carcinoma (RCC) has greatly expanded in the last decade. From being a malignancy orphan of effective therapies, kidney cancer has become today a tumor with several treatment options. Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). In this complex scenario it is important to find prognostic and predictive factors that can help in decision making in the treatment of mRCC.

  7. Identification of TGF-β-activated kinase 1 as a possible novel target for renal cell carcinoma intervention

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Fandong; Li, Yan; Tian, Xin; Fu, Liye; Yin, Yuanqin; Sui, Chengguang; Ma, Ping; Jiang, Youhong, E-mail: youyuanhongyeah@yeah.net

    2014-10-10

    Highlights: • Inhibition of TAK1 kinase activity suppresses NF-κB activation and RCC cell survival. • TAK1 inhibitors induces apoptotic cytotoxicity against RCC cells. • RCC cells with TAK1 depletion show reduced cell viability and increased apoptosis. • TAK1 and p-NF-κB are both over-expressed in human RCC tissues. • Inhibition or depletion of TAK1 enhances the activity of vinblastine sulfate. - Abstract: Renal cell carcinoma (RCC) is common renal malignancy within poor prognosis. TGF-β-activated kinase 1 (TAK1) plays vital roles in cell survival, apoptosis-resistance and carcinogenesis through regulating nuclear factor-κB (NF-κB) and other cancer-related pathways. Here we found that TAK1 inhibitors (LYTAK1, 5Z-7-oxozeanol (5Z) and NG-25) suppressed NF-κB activation and RCC cell (786-O and A489 lines) survival. TAK1 inhibitors induced apoptotic cytotoxicity against RCC cells, which was largely inhibited by the broad or specific caspase inhibitors. Further, shRNA-mediated partial depletion of TAK1 reduced 786-O cell viability whiling activating apoptosis. Significantly, TAK1 was over-expressed in human RCC tissues, and its level was correlated with phosphorylated NF-κB. Finally, kinase inhibition or genetic depletion of TAK1 enhanced the activity of vinblastine sulfate (VLB) in RCC cells. Together, these results suggest that TAK1 may be an important oncogene or an effective target for RCC intervention.

  8. Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Gatto, Francesco; Volpi, Nicola; Nilsson, Helén; Nookaew, Intawat; Maruzzo, Marco; Roma, Anna; Johansson, Martin E; Stierner, Ulrika; Lundstam, Sven; Basso, Umberto; Nielsen, Jens

    2016-05-24

    Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%-100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis. PMID:27184840

  9. Bone Metastasis from Renal Cell Carcinoma

    Science.gov (United States)

    Chen, Szu-Chia; Kuo, Po-Lin

    2016-01-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The “vicious cycle” hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden. PMID:27338367

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

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    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.

  11. Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji-Hee [Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Lkhagvadorj, Sayamaa; Lee, Mi-Ra [Department of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Hwang, Kyu-Hee [Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Chung, Hyun Chul; Jung, Jae Hung [Department of Urology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Cha, Seung-Kuy, E-mail: skcha@yonsei.ac.kr [Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of); Eom, Minseob, E-mail: eomm@yonsei.ac.kr [Department of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2014-05-23

    Highlights: • Orai1 channel is highly expressed in clear cell renal cell carcinoma (ccRCC) tissues. • Orai1 and STIM1 constitute a native store-operated Ca{sup 2+} entry in ccRCC cells. • Orai1 and STIM1 promote cell migration and proliferation of ccRCC cells. - Abstract: The intracellular Ca{sup 2+} regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca{sup 2+} entry (SOCE) is a major Ca{sup 2+} entry mechanism in non-excitable cells, being involved in cell proliferation and migration in several types of cancer. However, the expression and biological role of SOCE have not been investigated in clear cell renal cell carcinoma (ccRCC). Here, we demonstrate that Orai1 and STIM1, not Orai3, are crucial components of SOCE in the progression of ccRCC. The expression levels of Orai1 in tumor tissues were significantly higher than those in the adjacent normal parenchymal tissues. In addition, native SOCE was blunted by inhibiting SOCE or by silencing Orai1 and STIM1. Pharmacological blockade or knockdown of Orai1 or STIM1 also significantly inhibited RCC cell migration and proliferative capability. Taken together, Orai1 is highly expressed in ccRCC tissues illuminating that Orai1-mediated SOCE may play an important role in ccRCC development. Indeed, Orai1 and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration.

  12. Antitumoral effects of vasoactive intestinal peptide in human renal cell carcinoma xenografts in athymic nude mice.

    Science.gov (United States)

    Vacas, Eva; Arenas, M Isabel; Muñoz-Moreno, Laura; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2013-08-01

    We studied antitumor effect of VIP in human renal cell carcinoma (RCC) (A498 cells xenografted in immunosuppressed mice). VIP-treated cells gave resulted in p53 upregulation and decreased nuclear β-catenin translocation and NFκB expression, MMP-2 and MMP-9 activities, VEGF levels and CD-34 expression. VIP led to a more differentiated tubular organization in tumours and less metastatic areas. Thus, VIP inhibits growth of A498-cell tumours acting on the major issues involved in RCC progression such as cell proliferation, microenvironment remodelling, tumour invasion, angiogenesis and metastatic ability. These antitumoral effects of VIP offer new therapeutical possibilities in RCC treatment.

  13. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    Science.gov (United States)

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks.

  14. Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines

    OpenAIRE

    Sugiyama Takayuki; Teratani Takumi; Takayama Tatsuya; Takaoka Naohisa; Mugiya Soichi; Ozono Seiichiro

    2011-01-01

    Abstract Background Improving the treatment of renal cell carcinoma (RCC) will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7), also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC,...

  15. Cost-Effectiveness of Everolimus for Second-Line Treatment of Metastatic Renal Cell Carcinoma in Serbia

    NARCIS (Netherlands)

    Mihajlovic, Jovan; Pechlivanoglou, Petros; Sabo, Ana; Tomic, Zdenko; Postma, Maarten J.

    2013-01-01

    Background: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progre

  16. Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    NARCIS (Netherlands)

    Pischon, Tobias; Lahmann, Petra H; Boeing, Heiner; Tjønneland, Anne; Halkjaer, Jytte; Overvad, Kim; Klipstein-Grobusch, Kerstin; Linseisen, Jakob; Becker, Nikolaus; Trichopoulou, Antonia; Benetou, Vassiliki; Trichopoulos, Dimitrios; Sieri, Sabina; Palli, Domenico; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Monninkhof, Evelyn; Peeters, Petra H M; Bueno-de-Mesquita, H Bas; Büchner, Frederike L; Ljungberg, Börje; Hallmans, Göran; Berglund, Göran; González, Carlos Alberto; Dorronsoro Iraeta, Miren; Gurrea, Aurelio Barricarte; Navarro, Carmen A; Martínez-García, Carmen; Quirós, José Ramón; Roddam, Andrew; Allen, Naomi E; Bingham, Sheila A; Khaw, Kay-Tee; Kaaks, Rudolf; Norat, Teresa; Slimani, Nadia; Riboli, Elio

    2006-01-01

    Previous studies suggest that obesity is related to increased risk of renal cell carcinoma (RCC); however, only a few studies report on measures of central vs. peripheral adiposity. We examined the association between anthropometric measures, including waist and hip circumference and RCC risk among

  17. Chromophobe renal cell carcinoma: Comprehensive analysis of 11 cases

    Directory of Open Access Journals (Sweden)

    Rajendra B Nerli

    2015-01-01

    Full Text Available Background: Chromophobe renal cell carcinoma (chRCC is a subtype of RCC. chRCC is diagnosed mainly in sixth decade of life. An incidence of chRCC is similar in both men and woman. Eighty-six percent of chRCCs cases are diagnosed in early stages. To analyze the clinical behavior of chRCC, we retrospectively evaluated the data from our hospital. The aim of this study was to evaluate the incidence, clinical presentation, prognosis, and clinical outcome of chRCC in a retrospective series of nephrectomy specimens. Materials and Methods: We retrospectively looked at our hospital database, which included 318 patients who had undergone surgery for RCC between January 2000 and December 2013. Several parameters were noted in each patient, which included age, sex, symptoms at presentation, Eastern Cooperative Oncology Group performance status, tumor diameter, tumor node metastasis stage and grade, histologic cell type, follow-up time, local recurrence, disease progression, and death. Results: Of 318 patients included in the database, 11 (3.45% had chRCC. Preoperatively, 9 (81% had T1 lesions, and the remaining 2 (18.9% had T2 lesions. Of the T1 lesions, 6 had tumors ≤4 cm (T1a in diameter and the remaining 3 had tumors >4 cm (T1b in diameter. The mean survival of the patients was 99.27 ΁ 27 months. Conclusions: Our series confirms a favorable outcome for the chRCC subtype with little local aggressiveness and a low propensity for progression and death from cancer.

  18. Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Yong

    2013-02-01

    Full Text Available Abstract Background MYST1 (also known as hMOF, a member of the MYST family of histone acetyltransferases (HATs as an epigenetic mark of active genes, is mainly responsible for histone H4K16 acetylation in the cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here we examined the involvement of hMOF expression and histone H4K16 acetylation in primary renal cell carcinoma (RCC. Simultaneously, we investigated the correlation between the expression of hMOF and clear cell RCC (ccRCC biomarker carbohydrase IX (CA9 in RCC. Materials and methods The frozen RCC tissues and RCC cell lines as materials, the reverse transcription polymerase chain reaction (RT-PCR, western blotting and immunohistochemical staining approaches were used. Results RT-PCR results indicate that hMOF gene expression levels frequently downregulated in 90.5% of patients (19/21 with RCC. The reduction of hMOF protein in both RCC tissues and RCC cell lines is tightly correlated with acetylation of histone H4K16. In addition, overexpression of CA9 was detected in 100% of ccRCC patients (21/21. However, transient transfection of hMOF in ccRCC 786–0 cells did not affect both the gene and protein expression of CA9. Conclusion hMOF as an acetyltransferase of H4K16 might be involved in the pathogenesis of kidney cancer, and this epigenetic changes might be a new CA9-independent RCC diagnostic maker.

  19. The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

    NARCIS (Netherlands)

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

    2014-01-01

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

  20. AIF Downregulation and Its Interaction with STK3 in Renal Cell Carcinoma

    OpenAIRE

    Xu, Shengqiang; Wu, Hongjin; Nie, Huan; Yue, Lei; Jiang, Huadong; Xiao, Sheng; Li, Yu

    2014-01-01

    Apoptosis-inducing factor (AIF) plays a crucial role in caspase-independent programmed cell death by triggering chromatin condensation and DNA fragmentation. Therefore, it might be involved in cell homeostasis and tumor development. In this study, we report significant AIF downregulation in the majority of renal cell carcinomas (RCC). In a group of RCC specimens, 84% (43 out of 51) had AIF downregulation by immunohistochemistry stain. Additional 10 kidney tumors, including an oxyphilic adenom...

  1. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma

    Science.gov (United States)

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-01-01

    Abstract Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs.

  2. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma.

    Science.gov (United States)

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-06-01

    Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs. PMID:26091477

  3. Perfusion computed tomography in renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chandan; J; Das; Usha; Thingujam; Ananya; Panda; Sanjay; Sharma; Arun; Kumar; Gupta

    2015-01-01

    Various imaging modalities are available for the diagnosis, staging and response evaluation of patients with renal cell carcinoma(RCC). While contrast enhanced computed tomography(CT) is used as the standard of imaging for size, morphological evaluation and response assessment in RCC, a new functional imaging technique like perfusion CT(p CT), goes down to the molecular level and provides new perspectives in imaging of RCC. p CT depicts regional tumor perfusion and vascular permeability which are indirect parameters of tumor angiogenesis and thereby provides vital information regarding tumor microenvironment. Also response evaluation using p CT may predate the size criteria used in Response Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier following tissue kinase inhibitors before any actual change in size. This may potentially help in predicting prognosis, better selection of therapy and more accurate and better response evaluation in patients with RCC. This article describes the techniques and role of p CT in staging and response assessment in patients with RCCs.

  4. Systemic adjuvant therapies in renal cell carcinoma.

    Science.gov (United States)

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

    2012-10-01

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

  5. Systemic adjuvant therapies in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sebastiano Buti

    2012-10-01

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

  6. Hemangioblastoma and renal clear cell carcinoma distinguished by means of the AgNOR method.

    Science.gov (United States)

    Crocker, J; Carey, M P; Allcock, R

    1990-04-01

    In view of the difficulty encountered in distinguishing between 2 degrees renal cell carcinoma (RCC) and hemangioblastoma (HBl) in the central nervous system, the AgNOR technique has been applied empirically to a series of 16 specimens of HBl, 5 primary RCC, and 6 specimens of secondary RCC in the CNS. To avoid tautology, the nature of these was confirmed by immunostaining for epithelial membrane antigen (EMA) and factor VIII-related antigen (FVII RAg). It was found that mean nuclear AgNOR counts in the stromal and endothelial cells of HBl exceeded significantly the counts in the tumor and endothelial cells of RCC, with no overlap in values. It is suggested that the AgNOR method is a useful adjunct in achieving the differential diagnosis of HBl and RCC in the nervous system.

  7. Harnessing the p53-PUMA Axis to Overcome DNA Damage Resistance in Renal Cell Carcinoma

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    Xiaoguang Zhou

    2014-12-01

    Full Text Available Resistance to DNA damage–induced apoptosis is a hallmark of cancer and a major cause of treatment failure and lethal disease outcome. A tumor entity that is largely resistant to DNA-damaging therapies including chemo- or radiotherapy is renal cell carcinoma (RCC. This study was designed to explore the underlying molecular mechanisms of DNA damage resistance in RCC to develop strategies to resensitize tumor cells to DNA damage–induced apoptosis. Here, we show that apoptosis-resistant RCC cells have a disconnect between activation of p53 and upregulation of the downstream proapoptotic protein p53 upregulated modulator of apoptosis (PUMA. We demonstrate that this disconnect is not caused by gene-specific repression through CCCTC-binding factor (CTCF but instead by aberrant chromatin compaction. Treatment with an HDAC inhibitor was found to effectively reactivate PUMA expression on the mRNA and protein level and to revert resistance to DNA damage–induced cell death. Ectopic expression of PUMA was found to resensitize a panel of RCC cell lines to four different DNA-damaging agents tested. Remarkably, all RCC cell lines analyzed were wild-type for p53, and a knockdown was likewise able to sensitize RCC cells to acute genotoxic stress. Taken together, our results indicate that DNA damage resistance in RCC is reversible, involves the p53-PUMA axis, and is potentially targetable to improve the oncological outcomes of RCC patients.

  8. Present and future perspectives on immunotherapy for advanced renal cell carcinoma: Going to the core or beating around the bush?

    Directory of Open Access Journals (Sweden)

    Hidenori Kawashima

    2015-03-01

    Full Text Available Metastatic lesions of renal cell carcinoma (RCC occasionally regress spontaneously after surgical removal of the primary tumor. Although this is an exceptionally rare occurrence, RCC has thus been postulated to be immunogenic. Immunotherapies, including cytokine therapy, peptide-based vaccines, and immune checkpoint inhibitors have therefore been used to treat patients with advanced, metastatic RCC. We review the history, trends, and recent progress in immunotherapy for advanced RCC and discuss future perspectives, with consideration of our experimental work on galectin 9 and PINCH as promising specific immunotherapy targets. 

  9. 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.

  10. MicroRNA-194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Nofech-Mozes, Roy; Khella, Heba W Z; Scorilas, Andreas; Youssef, Leza; Krylov, Sergey N; Lianidou, Evi; Sidiropoulos, Konstantinos G; Gabril, Manal; Evans, Andrew; Yousef, George M

    2016-04-01

    Clear cell renal cell carcinoma (ccRCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in ccRCC. In a cohort of 234 patients with primary ccRCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary ccRCC (P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival (P = 0.041) and overall survival (P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194-positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in ccRCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses (P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. ccRCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in ccRCC. PMID:26860079

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

    Directory of Open Access Journals (Sweden)

    Ronald M. Bukowski

    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.

  12. More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, J.L.; Wang, F.L.; Yi, X.M.; Qin, W.J.; Wu, G.J. [Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China); Huan, Y. [Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China); Yang, L.J.; Zhang, G.; Yu, L.; Zhang, Y.T.; Qin, R.L.; Tian, C.J. [Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi' an, Shaanxi (China)

    2014-10-31

    Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

  13. CRISPR-Mediated VHL Knockout Generates an Improved Model for Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Schokrpur, Shiruyeh; Hu, Junhui; Moughon, Diana L; Liu, Peijun; Lin, Lucia C; Hermann, Kip; Mangul, Serghei; Guan, Wei; Pellegrini, Matteo; Xu, Hua; Wu, Lily

    2016-01-01

    Metastatic renal cell carcinoma (mRCC) is nearly incurable and accounts for most of the mortality associated with RCC. Von Hippel Lindau (VHL) is a tumour suppressor that is lost in the majority of clear cell RCC (ccRCC) cases. Its role in regulating hypoxia-inducible factors-1α (HIF-1α) and -2α (HIF-2α) is well-studied. Recent work has demonstrated that VHL knock down induces an epithelial-mesenchymal transition (EMT) phenotype. In this study we showed that a CRISPR/Cas9-mediated knock out of VHL in the RENCA model leads to morphologic and molecular changes indicative of EMT, which in turn drives increased metastasis to the lungs. RENCA cells deficient in HIF-1α failed to undergo EMT changes upon VHL knockout. RNA-seq revealed several HIF-1α-regulated genes that are upregulated in our VHL knockout cells and whose overexpression signifies an aggressive form of ccRCC in the cancer genome atlas (TCGA) database. Independent validation in a new clinical dataset confirms the upregulation of these genes in ccRCC samples compared to adjacent normal tissue. Our findings indicate that loss of VHL could be driving tumour cell dissemination through stabilization of HIF-1α in RCC. A better understanding of the mechanisms involved in this phenomenon can guide the search for more effective treatments to combat mRCC. PMID:27358011

  14. Current Status of Studies on Targeted Therapy for Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shaoqi Wang; Shaoxiang Wang; Juan Wang

    2008-01-01

    Renal cell carcinoma (RCC) is regarded as one of the most refractory malignancies. A further study of the molecular mechanism of RCC formation has led to a series of successful examples for treatment of patients with advanced RCC. Over the past 20 years, a nonspecific immunotherapy, with cytokines, has been employed as the gold standard for therapy of metastatic RCC. However, with scientific development and clinical testing of new drugs, targeted molecular cancer therapy has become a focus of interest. At the same time, with a better understanding of RCC,the treatment method has converged on anti-vascular endothelial growth factor (VEGF) and related molecular-targeted pathways.A large amount of research and numerous clinical trials have demonstrated the clinical efficacy of the targeted molecular therapies in patients with metastatic RCC. For example sorafenib and sunitinib were approved, in 2005 and 2006 respectively, by the U.S. FDA for treating advanced RCC. In this report, issues such as the importance of VEGF in RCC and the studies of bevacizumab,sunitinib and sorafenib in treating metastatic RCC etc., are reviewed.

  15. Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC. We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance

  16. Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma: plausible role in tumorigenesis.

    Science.gov (United States)

    Sharma, Ujjawal; Pal, Deeksha; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra

    2014-09-01

    Renal cell carcinoma (RCC) is the most common kidney cancer in adults. Although several genes have been found to be involved in carcinogenesis of RCC, more great efforts are needed to identify new genes which are responsible for the process. Clear cell RCC, originates from proximal tubule cells, is the most common pathological type of RCC. Alkaline phosphatase (ALP) is a marker enzyme of brush border membrane of proximal tubular cells. Our previous studies showed a significant decreased activity of Liver/Bone/Kidney (L/B/K) alkaline phosphatase in RCC. In the present study, we explored the molecular basis of the decreased activity of ALP in RCC. Immunohistochemistry, immunofluorescence and flow cytometry analysis showed decreased ALP protein in RCC. Additionally, real time PCR documented significantly reduced ALP gene expression (P = 0.009). Moreover, RCC cell lines (ACHN and A498) transfected with full length L/B/K cDNA showed decreased migratory property as well as viability of these cells as compared with controls (P = 0.000). Further, L/B/K ALP cDNA transfected cells (ACHN and A498) showed significant increased apoptosis as compared to control (P = 0.000). These findings suggest the new role of ALP in cell viability and apoptosis and involvement in RCC tumorigenesis. However, further studies are needed to explore the exact molecular mechanism. PMID:24909115

  17. Interferon-Gamma-Induced Nitric Oxide Inhibits the Proliferation of Murine Renal Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    David J. Tate Jr., John R. Patterson, Cruz Velasco-Gonzalez, Emily N. Carroll, Janie Trinh, Daniel Edwards, Ashok Aiyar, Beatriz Finkel-Jimenez, Arnold H. Zea

    2012-01-01

    Full Text Available Renal cell carcinoma (RCC remains one of the most resistant tumors to systemic chemotherapy, radiotherapy, and immunotherapy. Despite great progress in understanding the basic biology of RCC, the rate of responses in animal models and clinical trials using interferons (IFNs has not improved significantly. It is likely that the lack of responses can be due to the tumor's ability to develop tumor escape strategies. Currently, the use of targeted therapies has improved the clinical outcomes of patients with RCC and is associated with an increase of Th1-cytokine responses (IFNγ, indicating the importance of IFNγ in inhibiting tumor proliferation. Thus, the present study was designed to investigate a new mechanism by which IFNγ mediates direct anti-proliferative effects against murine renal cell carcinoma cell lines. When cultured RCC cell lines were exposed to murine recombinant IFNγ, a dose dependent growth inhibition in CL-2 and CL-19 cells was observed; this effect was not observed in Renca cells. Growth inhibition in CL-2 and CL-19 cell lines was associated with the intracellular induction of nitric oxide synthase (iNOS protein, resulting in a sustained elevation of nitric oxide (NO and citrulline, and a decrease in arginase activity. The inhibition of cell proliferation appears to be due to an arrest in the cell cycle. The results indicate that in certain RCC cell lines, IFNγ modulates L-arginine metabolism by shifting from arginase to iNOS activity, thereby developing a potent inhibitory mechanism to encumber tumor cell proliferation and survival. Elucidating the cellular events triggered by IFNγ in murine RCC cell lines will permit anti-tumor effects to be exploited in the development of new combination therapies that interfere with L-arginine metabolism to effectively combat RCC in patients.

  18. Multiple metastatic renal cell carcinoma isolated to pancreas.

    Science.gov (United States)

    Comunoğlu, Cem; Altaca, Gülüm; Demiralay, Ebru; Moray, Gökhan

    2012-06-01

    Renal cell carcinoma (RCC) metastases to the pancreas are reported to be rare. Isolated multiple pancreatic metastases are even rarer. We report a 68-year-old asymptomatic male patient who presented with multiple metastatic nodular lesions in the pancreas demonstrated by computerized tomography 3.5 years after radical nephrectomy performed for clear cell RCC. Spleen-preserving total pancreatectomy was performed. Gross examination revealed five well-demarcated tumoral nodules in the head, body and tail of the pancreas. Histopathological examination revealed clusters of epithelial clear cells, immunohistochemically positive for CD10 and vimentin, and negative for CK19 and chromogranin, supporting a diagnosis of metastatic RCC. The patient has remained well at 29 months post-resection, in agreement with recent experience that radical resection for multiple isolated metastatic nodular lesions can achieve improved survival and better quality of life.

  19. 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

  20. Nevoid Basal Cell Carcinoma Syndrome

    Science.gov (United States)

    ... Nevoid Basal Cell Carcinoma Syndrome Request Permissions Nevoid Basal Cell Carcinoma Syndrome Approved by the Cancer.Net Editorial Board , 04/2016 What is Nevoid Basal Cell Carcinoma Syndrome? Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is ...

  1. 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.

  2. Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

    Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods: The microculture tetrazolium (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53and c-myc. Results: As2O3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0 μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells,but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion: As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

  3. Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells.

    Science.gov (United States)

    Kobayashi, Minoru; Morita, Tatsuo; Chun, Nicole A L; Matsui, Aya; Takahashi, Masafumi; Murakami, Takashi

    2012-04-01

    There has been little information about metastatic behavior of renal cell carcinoma (RCC) cells because human cancers metastasize only rarely in immunodeficient mice. Moreover, it is difficult to know the effect of host immunity on RCC metastasis due to lack of such RCC cells as transplantable in not only xenograft models but also counterparts with intact immunity. Therefore, we scrutinized in vivo metastasis of RCC cells to seek for the optimal preclinical model to study metastatic behavior. The luciferase-expressing three representative human RCC cell lines (Caki-1, A498, and 786-O) and rat ACI-RCC cell which were established in our laboratory were transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice or immunocompetent ACI rats by intracardiac injection as well as orthotopic inoculation. Metastasis was monitored using a bioluminescent imaging technique. Metastasis was rare in the three human RCC cells even when they were directly disseminated into systemic circulation under the condition least susceptible to host immune attack in NOD/SCID mice. In contrast, ACI-RCC cells spontaneously metastasized to pulmonary tissue from orthotopic tumor sites and systemically spread via intracardiac route. Metastases were more extensive when the cells were inoculated into an immunodeficient host, implying suppressive effect of host immunity on colonization of RCC cells. These results suggest that the representative human RCC cells are not adequate resource to study metastasis but that the luciferase-labeled ACI-RCC cell characterized by its luminescent stability, enhanced tumorigenicity, and widespread metastatic potential provides a useful in vivo model for preclinical assessment of cancer progression and potential therapies against RCC.

  4. Serum ferritin in renal cell carcinoma: Effect of tumor size, volume grade, and stage

    OpenAIRE

    Singh Kamal; Singh S; Suri Amit; Vijjan Vivek; Goswami A; Khullar Madhu

    2005-01-01

    Aim: To study the levels of serum ferritin in patients of renal cell carcinoma (RCC). Patients and methods: Serum ferritin levels were measured preoperatively in 32 patients with radiological evidence of RCC using an enzyme immunoassay. The largest diameter of the primary tumor was measured in the pathological specimens in patients undergoing radical nephrectomy while in patients with nonoperable tumor maximum tumor dimension was taken from CT scan. Pathological staging was done according...

  5. Transesophageal echocardiography-guided thrombectomy of intracardiac renal cell carcinoma without cardiopulmonary bypass

    Science.gov (United States)

    Souki, Fouad Ghazi; Demos, Michael; Fermin, Lilibeth; Ciancio, Gaetano

    2016-01-01

    Advanced renal cell carcinoma (RCC) resection has important anesthetic management implications, particularly when tumor extends, suprahepatic, into the right atrium. Use of transesophageal echocardiogram (TEE) is essential in identifying tumor extension and guiding resection. Latest surgical approach avoids venovenous and cardiopulmonary bypass yet requires special precautions and interventions on the anesthesiologist's part. We present a case of Level IV RCC resected without cardiopulmonary bypass and salvaged by TEE guidance and detection of residual intracardiac tumor. PMID:27716710

  6. Management of Locally Advanced Renal Cell Carcinoma with Invasion of the Duodenum

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    Andrew T. Schlussel

    2013-01-01

    Full Text Available Renal cell carcinoma (RCC is rare but aggressive, with greater than 20% of patients presenting with stage III or IV, disease. Surgical resection of the primary tumor regardless of stage is the treatment of choice, and en bloc resection of involved organs provides the only potential chance for cure. This case report describes a patient with metastatic right-sided RCC with invasion of the inferior vena cava and duodenum managed by en block resection and pancreaticoduodenectomy. This report will review the workup and treatment of locally advanced RCC, as well as the role of cytoreductive nephrectomy in the setting of metastatic disease.

  7. Synchronous Type 1 Papillary Renal Cell Carcinoma in a Patient with Rectal Adenocarcinoma.

    Science.gov (United States)

    Piao, Jinhua; Friedman, Paul; Siddiqui, Sameer; Veerapong, Jula; Lai, Jin-Ping

    2016-09-01

    Synchronous colorectal cancer (CRC) and renal cell carcinoma (RCC) is relatively rare, particularly when the synchronous RCC is of papillary subtype, which is exceedingly rare. We report a case of a 63-year-old Caucasian man with synchronous CRC and type 1 papillary RCC. After the patient presented with three episodes of melena, colonoscopy followed by biopsy confirmed rectal adenocarcinoma. The computed tomographic imaging also showed an incidental mass of the upper pole of the left kidney suspicious for RCC. Once chemoradiation therapy was successfully completed, an ultra low anterior resection and partial nephrectomy were performed concurrently. Histological examination showed colorectal adenocarcinoma (ypT1 N0 Mx) and papillary RCC type I (pT1a Nx Mx). Although the exact pathogenesis of synchronous CRC and RCC is unknown, it has been suggested that almost all patients with this entity do not have Lynch syndrome. The majority of these patients usually present with CRC-related symptoms and then, during workup, are subsequently found to have an incidental renal mass that is most often diagnosed as clear cell subtype of RCC. To the best of our knowledge, this is only the second reported case of synchronous CRC and type 1 papillary RCC. PMID:27630335

  8. Combined treatment of tyrosine kinase inhibitor labeled gold nanorod encapsulated albumin with laser thermal ablation in a renal cell carcinoma model

    Science.gov (United States)

    This manuscript served to characterize and evaluate Human Serum Albumin-encapsulated Nanoparticles (NPs) for drug delivery of a tyrosine kinase inhibitor combined with induction of photothermal ablation (PTA) combination therapy of Renal Cell Carcinoma (RCC). RCC is the most common type of kidney c...

  9. c-Myc modulates glucose metabolism via regulation of miR-184/PKM2 pathway in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Huang, Jiwei; Kong, Wen; Zhang, Jin; Chen, Yonghui; Xue, Wei; Liu, Dongming; Huang, Yiran

    2016-10-01

    Renal cell carcinoma (RCC) is one of the most malignant tumors worldwide. Among all subtypes of RCC, clear-cell RCC (ccRCC) is the most common and aggressive one. The difficulty in overcoming resistance of traditional treatment is a threat for ccRCC therapies. Therefore, to understand the mechanism that underlies ccRCC progression is critical for new drug development. In the present study, we identified that miR-184 could be downregulated by c-Myc, which is different from the standard opinion that c-Myc is a target of miR-184. Overexpression of pre-miR-184 changed the metabolic and proliferation features of ccRCC cells by reducing cell glucose consumption, lactate production and cell proliferation. Further analysis by computer bioinformatics revealed that PKM2 is a target of miR-184. Both PKM2 mRNA and protein were significantly affected by addition of miR-184. Importantly, the PKM2 expression level was indeed increased in ccRCC samples, which is totally reverse compared to the decreased miR-184 expression level. Interestingly, we found that when PKM2 was knocked down in ccRCC cells, the rapid proliferation, high glucose consumption and high lactate production were all clearly inhibited, which indicates metabolic reprogramming and cancer progression blocking the in ccRCC cells. Our findings shed new light on ccRCC molecular study and provide a new and solid basis for developing ccRCC therapy.

  10. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

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    Quiroga-Garza Gabriela

    2012-02-01

    Full Text Available Abstract Seven percent of renal cell carcinoma (RCC cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC and a tubulocystic renal carcinoma (TCRC in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR and distal tubule cell (CK19 markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2 of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3 showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283

  11. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    Faria, J.

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  12. Epidemiologic characteristics of renal cell carcinoma in Brazil

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    Aguinaldo C. Nardi

    2010-04-01

    Full Text Available PURPOSE: In Brazil, National data regarding the epidemiology of renal cell carcinoma (RCC are scarce. The aim of this study was to describe the demographic, clinical, and pathologic characteristics of RCC diagnosed and treated by members of the SBU - Brazilian Society of Urology. MATERIALS AND METHODS: For this cross-sectional study, data were collected through an on line questionnaire available to the members of the Brazilian Society of Urology (SBU. Between May 2007 and May 2008, voluntary participant urologists collected data on demographic, clinical and pathological characteristics from patients diagnosed with RCC in their practice. RESULTS: Fifty SBU affiliated institutions contributed with patient information to the study. Of the 508 patients, 58.9% were male, 78.9% were white, and the mean age was 59.8 years. Smoking history, high blood pressure and a body mass index above 30 kg/m2 were present in 14.8%, 46.1% and 17.9% of the patients, respectively. Abdominal ultrasound and computed tomography were the main diagnostic methods. The majority of the cases were localized tumors and metastasis were presented in 9.5% of the patients; 98.4% underwent nephrectomy. Clear cell carcinoma was the most common histological type. In comparison with private institutions, stage IV disease was less frequent among patients treated at public health services (P = 0.033. CONCLUSIONS: RCC in Brazil is more common in white men in their sixth decade of life. Ultrasound is the main diagnostic tool for the diagnosis of clear cell carcinoma and we found that localized disease was predominant. A national registry of RCC is feasible and may provide valuable information.

  13. Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    屈凤莲; 李艳芬; 万云霞; 马建辉; 石卫; 储大同; 孙燕

    2004-01-01

    Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods. The microculture tetrazolium (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cytometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse transcription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc. Results: As2O3 inhibited the growth of ROC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells, but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion. As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

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

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    Ak, I.; Can, C. [Osmangazi Univ. Medical Faculty, Eskisehir (Turkey). Depts. of Nuclear Medicine and Urology

    2005-12-01

    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.

  15. MET Inhibition in Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

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

    2016-01-01

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

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

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    Chiara Paglino

    2011-12-01

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

  17. The von Hippel-Lindau protein sensitizes renal carcinoma cells to apoptotic stimuli through stabilization of BIMEL

    OpenAIRE

    Guo, Y; Schoell, MC; Freeman, RS

    2009-01-01

    von Hippel-Lindau (VHL) disease is caused by germ-line mutations in the VHL tumor suppressor gene and is the most common cause of inherited renal cell carcinoma (RCC). Mutations in the VHL gene also occur in a large majority of sporadic cases of clear-cell RCC, which have high intrinsic resistance to chemotherapy and radiotherapy. Here we show that VHL-deficient RCC cells express lower levels of the pro-apoptotic Bcl-2 family protein BIMEL and are more resistant to etoposide and UV radiation ...

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

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    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.

  19. Percutaneous Cryoablation for Renal Cell Carcinoma

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    Tsitskari Maria

    2015-06-01

    Full Text Available Renal cell carcinoma (RCC is the most common type of kidney cancer in adults. Nephron sparing resection (partial nephrectomy has been the “gold standard” for the treatment of resectable disease. With the widespread use of cross sectional imaging techniques, more cases of renal cell cancers are detected at an early stage, i.e. stage 1A or 1B.  This has provided an impetus for expanding the nephron sparing options and especially, percutaneous ablative techniques.  Percutaneous ablation for RCC is now performed as a standard therapeutic nephron-sparing option in patients who are poor candidates for resection or when there is a need to preserve renal function due to comorbid conditions, multiple renal cell carcinomas, and/or heritable renal cancer syndromes. During the last few years, percutaneous cryoablation has been gaining acceptance as a curative treatment option for small renal cancers. Clinical studies to date indicate that cryoablation is a safe and effective therapeutic method with acceptable short and long term outcomes and with a low risk, in the appropriate setting.  In addition it seems to offer some advantages over radio frequency ablation (RFA and other thermal ablation techniques for renal masses.

  20. Papillary Renal Cell Carcinoma Arising in a Lymph Node Metastasis of a Testicular Teratoma: A Very Rare Occurrence.

    Science.gov (United States)

    Ozturk Sari, Sule; Ozluk, Yasemin; Taskin, Orhun Cig; Polat, Beldan; Ozturk, Ilker; Ekenel, Meltem; Kilicaslan, Isin; Bilgic, Bilge

    2016-08-01

    We present a case of a teratoma with somatic type malignancy (TSM) in the form of papillary renal cell carcinoma (pRCC) within supraclavicular and retroperitoneal lymph node metastases of a testicular pure teratoma. Resection of both masses revealed a teratoma without any other germ cell tumor component. A papillary carcinoma component was also detected intermingled with the teratomatous elements. The carcinoma cells displayed eosinophilic cytoplasm and prominent nucleoli. Groups of foamy histiocytes in the fibrovascular cores was a striking finding that brought pRCC to mind. Immunoreactivity for CK7, PAX8, AMACR, CD10, napsin, and vimentin along with morphologic findings confirmed renal cell differentiation. No radiological evidence of a primary renal cell carcinoma was found in the kidney. Consequently, pRCC arising in a teratoma was diagnosed. TSM is described as teratoma with a malignant component that is typically encountered in other organs and tissues. TSM in the form of pRCC is an extremely rare entity. Our case is the second example of a testicular germ cell tumor metastasis with a somatic malignancy in the form of pRCC. In conclusion, carcinomas of renal cell differentiation should be kept in mind as a rare form of TSM, especially in metastatic germ cell tumors. PMID:26936856

  1. RhoB Acts as a Tumor Suppressor That Inhibits Malignancy of Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    Ma, Xin; Zhang, Peng; Gao, Yu; Fan, Yang; Pang, Haigang; Gong, Huijie; Shen, Donglai; Gu, Liangyou; Zhang, Yu

    2016-01-01

    This study aims to investigate the biological role of RhoB in clear cell renal cell carcinoma (ccRCC). The expression of RhoB was examined in specimens of patients and cell lines by Western blot and Immunohistochemistry. The correlation between RhoB expression and clinicopathologic variables was also analyzed. The effects of RhoB on cell proliferation, cell cycle, cell apoptosis, and invasion/migration were detected by over-expression and knockdown of RhoB level in ccRCC cells via plasmids and RNAi. The results showed that RhoB was low-expressed in ccRCC surgical specimens and cell lines compared with adjacent normal renal tissues and normal human renal proximal tubular epithelial cell lines (HKC), and its protein expression level was significantly associated with the tumor pathologic parameter embracing tumor size(P = 0.0157), pT stage(P = 0.0035), TNM stage(P = 0.0024) and Fuhrman tumor grade(P = 0.0008). Further, over-expression of RhoB remarkably inhibited the cancer cell proliferation, colony formation and promoted cancer cell apoptosis, and aslo reduced the invasion and migration ability of ccRCC cells. Interestingly, up-regulation of RhoB could induce cell cycle arrest in G2/M phase and led to cell cycle regulators(CyclineB1,CDK1) and pro-apoptotic protein(casp3,casp9) aberrant expression. Moreover, knockdown of RhoB in HKC cells promoted cell proliferation and migration. Taken together, our study indicates that RhoB expression is decreased in ccRCC carcinogenesis and progression. Up-regulation of RhoB significantly inhibits ccRCC cell malignant phenotype. These findings show that RhoB may play a tumor suppressive role in ccRCC cells, raising its potential value in futural therapeutic target for the patients of ccRCC. PMID:27384222

  2. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma

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    Bukowski RM

    2011-08-01

    Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USAAbstract: The management of renal cell carcinoma (RCC has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus, and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α. The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients

  3. A Unique Presentation of an Undiagnosed Renal Cell Carcinoma

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    Georgios Kravvas

    2014-01-01

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

  4. Immunohistochemical distinction of renal cell carcinoma from other carcinomas with clear-cell histomorphology: utility of CD10 and CA-125 in addition to PAX-2, PAX-8, RCCma, and adipophilin.

    Science.gov (United States)

    Mentrikoski, Mark J; Wendroth, Scott M; Wick, Mark R

    2014-10-01

    Clear-cell renal cell carcinoma (CC-RCC) is the most common primary kidney malignancy, yet this morphology is not unique to renal primary tumors, as clear-cell variants of numerous nonrenal carcinomas of varying lineages exist. Therefore, because of CC-RCC's ability to metastasize to nearly any anatomic location, ancillary studies such as immunohistochemistry are often needed to establish the diagnosis. Despite CD10 and renal cell carcinoma monoclonal antibody (RCCma) being touted as sensitive and specific markers, some have suggested that more recent stains including PAX-2, PAX-8, or adipophilin (ADP) are more robust markers of CC-RCC. In this study, 26 cases of CC-RCC, and 51 nonrenal carcinomas with clear-cell histomorphology (CCM) were stained with CD10, RCCma, PAX-2, PAX-8, and ADP. CA-125 was also included to help distinguish CC-RCC from Müllerian clear-cell carcinomas, due the known expression of PAX-2 and PAX-8 in both these entities. RCCma highlighted 77% of CC-RCC and 27% of the CCM group, whereas CD10 was positive in 85% and 25%, respectively. ADP highlighted all CC-RCC and 45% of CCMs. PAX-2 was positive in 81% of CC-RCC and 24% of CCM, whereas PAX-8 stained 100% of CC-RCC and 39% of CCM. Müllerian-derived tumors (clear-cell carcinomas of the ovary, vagina, and cervix) were positive with PAX-2 and PAX-8 in 69% and 100% of cases, respectively. No cases of CC-RCC stained with CA-125, whereas 88% of the Müllerian-derived tumors were positive. In summary, although new markers such as PAX-2 and PAX-8 tend to be more sensitive markers of CC-RCC, they lose specificity when Müllerian tumors are included. Inclusion of a classic renal marker such as CD10 or RCCma in the immunohistochemical panel, as well as CA-125 obviates this difficulty.

  5. High expression of pituitary tumor-transforming gene-1 predicts poor prognosis in clear cell renal cell carcinoma

    Science.gov (United States)

    WEI, CAN; YANG, XIAOLIANG; XI, JUNHUA; WU, WEI; YANG, ZHENXING; WANG, WEI; TANG, ZHIGUO; YING, QUANSHENG; ZHANG, YANBIN

    2015-01-01

    Pituitary tumor-transforming gene-1 (PTTG1) is a recently identified oncogene involved in the progression of malignant tumors; however, the expression level of PTTG1 in clear cell renal cell carcinoma (ccRCC) and its potential value as a novel prognostic marker for ccRCC remains unclear. In this study, PTTG1 mRNA and protein levels were assessed in 44 paired ccRCC tissues and adjacent normal tissues by quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. Further immunohistochemical analysis was implemented in 192 samples of ccRCC to evaluate the associations between PTTG1 levels and the clinical characteristics in ccRCC. Reverse transcription qPCR and immunohistochemical analysis demonstrated that the PTTG1 mRNA and protein levels were significantly higher in ccRCC compared to normal tissues. In addition, the PTTG1 protein level in 192 ccRCC samples was found to be significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, whereas it was not associated with age and gender. Patients with low PTTG1 levels exhibited a better survival outcome compared to those with a higher PTTG1 level. PTTG1 expression and N stage were identified as independent prognostic factors for the overall survival of ccRCC patients. The results suggested that the overexpression of PTTG1 indicates a poor prognosis in ccRCC patients and, therefore, PTTG1 may serve as a novel prognostic marker for ccRCC. PMID:25798272

  6. Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

    OpenAIRE

    Farace, F.; Gross-Goupil, M; Tournay, E; Taylor, M; Vimond, N.; Jacques, N; Billiot, F.; Mauguen, A.; Hill, C.; Escudier, B

    2011-01-01

    Background: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) a...

  7. Advances of multidetector computed tomography in the characterization and staging of renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Athina; C; Tsili; Maria; I; Argyropoulou

    2015-01-01

    Renal cell carcinoma(RCC) accounts for approximately 90%-95% of kidney tumors. With the widespread use of cross-sectional imaging modalities, more than half of RCCs are detected incidentally, often diagnosed at an early stage. This may allow the planning of more conservative treatment strategies. Computed tomography(CT) is considered the examination of choice for thedetection and staging of RCC. Multidetector CT(MDCT) with the improvement of spatial resolution and the ability to obtain multiphase imaging, multiplanar and threedimensional reconstructions in any desired plane brought about further improvement in the evaluation of RCC. Differentiation of RCC from benign renal tumors based on MDCT features is improved. Tumor enhancement characteristics on MDCT have been found closely to correlate with the histologic subtype of RCC, the nuclear grade and the cytogenetic characteristics of clear cell RCC. Important information, including tumor size, localization, and organ involvement, presence and extent of venous thrombus, possible invasion of adjacent organs or lymph nodes, and presence of distant metastases are provided by MDCT examination. The preoperative evaluation of patients with RCC was improved by depicting the presence or absence of renal pseudocapsule and by assessing the possible neoplastic infiltration of the perirenal fat tissue and/or renal sinus fat compartment.

  8. 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)

    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

  9. Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma.

    Science.gov (United States)

    Fang, Lu; Zhang, Meng; Chen, Lei; Xiong, Hu; Ge, Yukun; Lu, Wei; Wu, Xun; Heng, Baoli; Yu, Dexin; Wu, Song

    2016-09-01

    Nucleolar and spindle-associated protein 1 (NUSAP1) is a microtubule-binding protein that plays an essential role in mitosis and cancer. Previous studies have demonstrated that NUSAP1 expression is relatively elevated in several malignancies. However, the biological roles of NUSAP1 in renal cell carcinoma (RCC) remain unknown. In the present study, we firstly performed reverse transcription‑polymerase chain reaction (RT-PCR) and western blot analysis to reveal that the expression of NUSAP1 was relatively elevated in clear cell RCC (ccRCC) tissue specimens and RCC cell lines. Immunohistochemical analysis showed that upregulation of NUSAP1 was significantly correlated with Fuhrman grade (P<0.001), tumor size (P=0.016), clinical stage (P<0.001) and distant metastasis (P=0.023). Additionally, high expression of NUSAP1 was closely associated with a shorter overall survival time of the ccRCC patients (P=0.006). Furthermore, we investigated the biological behaviors of RCC cells in vitro, and we identified that NUSAP1 depletion inhibited RCC cell migration, proliferation and invasion, and apoptosis was induced and the cell cycle was arrested. On the basis of our studies, NUSAP1 was identified as a potential prognostic indicator and a novel therapeutic target for RCC patients. PMID:27461786

  10. The von Hippel-Lindau protein sensitizes renal carcinoma cells to apoptotic stimuli through stabilization of BIMEL

    Science.gov (United States)

    Guo, Y; Schoell, MC; Freeman, RS

    2009-01-01

    von Hippel-Lindau (VHL) disease is caused by germ-line mutations in the VHL tumor suppressor gene and is the most common cause of inherited renal cell carcinoma (RCC). Mutations in the VHL gene also occur in a large majority of sporadic cases of clear-cell RCC, which have high intrinsic resistance to chemotherapy and radiotherapy. Here we show that VHL-deficient RCC cells express lower levels of the pro-apoptotic Bcl-2 family protein BIMEL and are more resistant to etoposide and UV radiation induced death compared to the same cells stably expressing the wild type VHL protein (pVHL). Re-introducing pVHL into VHL-null cells increased the half-life of BIMEL protein without affecting its mRNA expression, and over-expressing pVHL inhibited BIMEL polyubiquitination. Suppressing pVHL expression with RNA interference resulted in a decrease in BIMEL protein and a corresponding decrease in the sensitivity of RCC cells to apoptotic stimuli. Directly inhibiting BIMEL expression in pVHL-expressing RCC cells caused a similar decrease in cell death. These results demonstrate that pVHL acts to promote BIMEL protein stability in RCC cells, and that destabilization of BIMEL in the absence of pVHL contributes to the increased resistance of VHL-null RCC cells to certain apoptotic stimuli. PMID:19305426

  11. The von Hippel-Lindau protein sensitizes renal carcinoma cells to apoptotic stimuli through stabilization of BIM(EL).

    Science.gov (United States)

    Guo, Y; Schoell, M C; Freeman, R S

    2009-04-23

    von Hippel-Lindau (VHL) disease is caused by germ-line mutations in the VHL tumor suppressor gene and is the most common cause of inherited renal cell carcinoma (RCC). Mutations in the VHL gene also occur in a large majority of sporadic cases of clear-cell RCC, which have high intrinsic resistance to chemotherapy and radiotherapy. Here we show that VHL-deficient RCC cells express lower levels of the proapoptotic Bcl-2 family protein BIM(EL) and are more resistant to etoposide and UV radiation-induced death compared to the same cells stably expressing the wild-type VHL protein (pVHL). Reintroducing pVHL into VHL-null cells increased the half-life of BIM(EL) protein without affecting its mRNA expression, and overexpressing pVHL inhibited BIM(EL) polyubiquitination. Suppressing pVHL expression with RNA interference resulted in a decrease in BIM(EL) protein and a corresponding decrease in the sensitivity of RCC cells to apoptotic stimuli. Directly inhibiting BIM(EL) expression in pVHL-expressing RCC cells caused a similar decrease in cell death. These results demonstrate that pVHL acts to promote BIM(EL) protein stability in RCC cells, and that destabilization of BIM(EL) in the absence of pVHL contributes to the increased resistance of VHL-null RCC cells to certain apoptotic stimuli. PMID:19305426

  12. Pathological clavicular fracture as ifrst presentation of renal cell carcinoma:a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Yan Kong; Jin Wang; Huan Li; Peng Guo; Jian-Fa Xu; He-Lin Feng

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 3%of all cancer cases. RCCs usually metastasize to the lungs, bones, liver, or brain. Only<1%of patients with bone metastases manifested clavicular RCC metastases. hTus, clavicular metastasis as the initial presentation of RCC is extremely rare. We report a patient with RCC metastasis to the letf clavicle, which was ifrst presented with pain caused by a pathological fracture. Magnetic resonance image revealed a renal tumor, and technetium-99m–methylene diphosphonate bone scintigraphy showed multiple osseous metastases. The patient eventually underwent surgery to remove the lateral end of the letf clavicle and right kidney. Histopathology revealed renal tumor and clear cell carcinoma in the clavicle. Finally, we review 17 cases of clavicular metastases originating from different malignancies.

  13. 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...

  14. Effect of arginase II on L-arginine depletion and cell growth in murine cell lines of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Patterson John R

    2008-09-01

    Full Text Available Abstract Background L-arginine is the common substrate for the two isoforms of arginase. Arginase I, highly expressed in the liver and arginase II mainly expressed in the kidney. Arginase I-producing myeloid derived suppressor cells have been shown to inhibit T-cell function by the depletion of L-arginine. On the other hand, arginase II has been detected in patients with cancer and is thought to metabolize L-arginine to L-ornithine needed to sustain rapid tumor growth; however its role in L-arginine depletion is unclear. Thus, in tumor biology, L-arginine metabolism may play a dual role in tumor growth and in the induction of T cell dysfunction. Therefore, we studied in murine renal cell carcinoma (RCC cell lines, the effect of arginase II on tumor cell proliferation and L-arginine depletion. The effect of arginase inhibitors on cell proliferation was also tested. Methods Three murine renal cell carcinoma (mRCC cell lines were tested for the presence of arginase. nor-NOHA, an arginase inhibitor was used to substantiate the effect of arginase on cell growth and L-arginine depletion. Amino acid levels were tested by HPLC. Results Our results show that mRCC cell lines express only arginase II and were able to deplete L-arginine from the medium. Cell growth was independent of the amount of arginase activity expressed by the cells. nor-NOHA significantly (P = 0.01 reduced arginase II activity and suppressed cell growth in cells exhibiting high arginase activity. The depletion of L-arginine by mRCC induced the decrease expression of CD3ζ a key element for T-cell function. Conclusion The results of this study show for the first time that arginase II produced by RCC cell lines depletes L-arginine resulting in decreased expression of CD3ζ. These results indicate that RCC cell lines expressing arginase II can modulate the L-arginine metabolic pathway to regulate both cell growth and T-cell function. Blocking arginase may lead to a decrease in RCC cell

  15. Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment

  16. Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jiancheng [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wu, Kaijie [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Gao, Dexuan [Department of Urology, Shandong Provincial Hospital affiliated with Shandong University, Ji' nan (China); Zhu, Guodong; Wu, Dapeng; Wang, Xinyang; Chen, Yule; Du, Yuefeng; Song, Wenbin; Ma, Zhenkun [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Authement, Craig; Saha, Debabrata [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong, E-mail: jt.hsieh@utsouthwestern.edu [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); He, Dalin, E-mail: dalinhe@yahoo.com [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China)

    2014-11-15

    Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.

  17. Serum sclerostin levels in renal cell carcinoma patients with bone metastases

    Science.gov (United States)

    Wibmer, C.; Amrein, K.; Fahrleitner-Pammer, A.; Gilg, M. M.; Berghold, A.; Hutterer, G. C.; Maurer-Ertl, W.; Gerger, A.; Leithner, A.; Pichler, M.; Szkandera, J.

    2016-01-01

    Sclerostin has been proposed as a potent inhibitor of bone formation. Sclerostin antibodies are under clinical development to treat osteoporosis and metastatic bone disease. Serum sclerostin level is elevated in multiple myeloma, an osteolytic malignancy, where it might serve as predictive marker for the use of sclerostin-directed antibodies. As renal cell carcinoma (RCC) patients often present with osteolytic metastases, we aimed to investigate serum sclerostin levels in RCC patients. Our study included 53 RCC patients (19 with bone metastases, 25 with visceral metastases and 9 with localized disease) and 53 age- and gender-matched non-osteoporotic controls. Frozen serum samples were subjected to sclerostin quantitative sandwich ELISA. The mean serum sclerostin levels of RCC patients and controls were 45.8 pmol/l and 45.1 pmol/l, respectively (p = 0.86). Analysis of variance showed no difference between the subgroups of RCC patients with regard to visceral or bone metastases or localized disease (p = 0.22). There was no significant association between eGFR (estimated glomerular filtration rate) and serum sclerostin levels in RCC patients (r = 0.05; p = 0.74) and controls (r = 0.06; p = 0.68). Our results indicate that serum sclerostin levels appear not to be a valuable biomarker to assess the occurrence of bone metastases in RCC patients. PMID:27666393

  18. EVALUATION OF STEROID HORMONES AND THEIR RECEPTORS IN DEVELOPMENT AND PROGRESSION OF RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Nigel Bennett

    2014-06-01

    Full Text Available Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC, with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

  19. Renal Cell Carcinoma Metastasis from Biopsy Associated Hematoma Disruption during Robotic Partial Nephrectomy

    Directory of Open Access Journals (Sweden)

    Christopher Caputo

    2014-01-01

    Full Text Available We describe a case in which a patient with a past medical history of ovarian cancer received a diagnostic renal biopsy for an incidentally discovered renal mass. During left robotic partial nephrectomy (RPN, a perinephric hematoma was encountered. The hematoma was not present on preoperative imaging and was likely a result of the renal biopsy. The renal cell carcinoma (RCC and the associated hematoma were widely excised with negative surgical margins. On follow-up imaging at five months postoperatively, a recurrent renal mass at the surgical resection bed and several new nodules in the omentum were detected. During completion left robotic total nephrectomy and omental excision, intraoperative frozen sections confirmed metastatic RCC. We believe that a hematoma seeded with RCC formed as a result of the renal biopsy, and subsequent disruption of the hematoma during RPN caused contamination of RCC into the surrounding structures.

  20. Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control

    OpenAIRE

    Robinson William; Lewis Karl; Flaig Thomas; Gonzalez Rene; Schefter Tracey E; Kavanagh Brian D; Stinauer Michelle A; Chidel Mark; Glode Michael; Raben David

    2011-01-01

    Abstract Background Melanoma and renal cell carcinoma (RCC) are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT) involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies. Methods The records of patients with metastatic melanoma (n = 17 patients, 28 lesions) or RCC (n = 13 patients, 25 lesions) t...

  1. Body composition by computed tomography as a predictor of toxicity in patients with renal cell carcinoma treated with sunitinib.

    LENUS (Irish Health Repository)

    Cushen, Samantha J

    2014-04-21

    Sunitinib is a standard first-line option for metastatic renal cell carcinoma (mRCC). Body composition is a prognostic factor in cancer patients and patients with loss of skeletal muscle mass and fat-free mass (FFM) are prone to dose-limiting toxicity (DLT) during targeted drug therapy. We investigated whether body composition by computed tomography predicted DLT from sunitinib in mRCC.

  2. Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram

    OpenAIRE

    Liangyou Gu; Xin Ma; Hongzhao Li; Luyao Chen; Yongpeng Xie; Chaofei Zhao; Guoxiong Luo; Xu Zhang

    2016-01-01

    To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four mark...

  3. Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC)

    OpenAIRE

    Pischon, T.; Lahmann, PH; Boeing, H.; Tjonneland, A; Halkjaer, J; Overvad, K; Klipstein-Grobusch, K.; Linseisen, J.; N. Becker; Trichopoulou, A.; Benetou, V; Trichopoulos, D.; Sieri, S.; Palli, D.; Tumino, R.

    2006-01-01

    Previous studies suggest that obesity is related to increased risk of renal cell carcinoma (RCC); however, only a few studies report on measures of central vs. peripheral adiposity. We examined the association between anthropometric measures, including waist and hip circumference and RCC risk among 348,550 men and women free of cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 6.0 years of follow-up we identified 287 inciden...

  4. Renal cell carcinoma containing macroscopic fat on CT mimics an angiomyolipoma due to bone metaplasia without macroscopic calcification

    OpenAIRE

    Richmond, L; M. Atri; Sherman, C; Sharir, S

    2010-01-01

    We report a case of renal cell carcinoma (RCC) containing foci of macroscopic fat, which were pathologically proven to be areas of osseous metaplasia. The macroscopic fat was not associated with calcification on the pre-operative CT scan. To our knowledge, there are no reported cases of RCC that contain osseous metaplasia without evidence of macroscopic calcification on CT. The finding is significant because standard imaging practice is to classify a renal mass containing intratumoral macrosc...

  5. Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report

    Science.gov (United States)

    Acar, Ömer; Mut, Tuna; Sağlıcan, Yeşim; Sag, Alan Alper; Falay, Okan; Selcukbiricik, Fatih; Tabak, Levent; Esen, Tarık

    2016-01-01

    Introduction Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. Case presentation A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. Discussion Late recurrence of RCC has been reported to occur in 10–20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. Conclusion To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnostic. PMID:26874583

  6. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial

    DEFF Research Database (Denmark)

    Ravaud, Alain; Hawkins, Robert; Gardner, Jason P;

    2008-01-01

    was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. PATIENTS AND METHODS: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number...... grades) for lapatinib were rash (44%) and diarrhea (40%). CONCLUSION: Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT...

  7. Initial Presentation of Renal Cell Carcinoma as a Metastatic Mass within the Masseter Muscle: A Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyung Eun; Lee, Han Bee; Cho, Woo Ho; Kim, Jae Hyung; Lee, Ji Hae; Kang, Min Jin [Dept. of Radiology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Kim, Hyun Jung [Dept. of Pathology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

    2012-02-15

    Renal cell carcinoma (RCC) is often concomitant with distant metastasis, and these metastases are the first sign of an otherwise occult primary. Whereas metastasis of RCC to the head and neck has been reported, metastasis to the masseter muscle, which is composed of skeletal muscle, is quite rare. We now report the case of a 66-year-old man who had a past history of pulmonary tuberculosis, with RCC metastasis of a well-defined intensely enhancing hypervascular mass in the masseter muscle as the initial presentation. We present the imaging findings of this case and a literature review about radiologic differential diagnosis of intramasseteric masses.

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

    Science.gov (United States)

    Ferraz de Campos, Fernando Peixoto; Narvaez, Margarita Rosa Aveiga; Reis, Paola Vasconcellos Soares; Gomes, Augusto Cesar Marins; Paraskevopoulos, Daniela Kallíope de Sá; Santana, Frederico; Fugita, Oscar Eduardo Hidetoshi

    2016-01-01

    Acanthosis nigricans (AN), an entity recognized since the 19th century, is a dermatopathy associated with insulin-resistant conditions, endocrinopathies, drugs, chromosome abnormalities and neoplasia. The latter, also known as malignant AN, is mostly related to abdominal neoplasms. Malignant AN occurs frequently among elderly patients. In these cases, the onset is subtle, and spreading involves the flexural regions of the body, particularly the axillae, palms, soles, and mucosa. Gastric adenocarcinoma is the most frequent associated neoplasia, but many others have been reported. Renal cell carcinoma (RCC), although already reported, is rarely associated with malignant AN. The authors report the case of a woman who was being treated for depression but presented a long-standing and marked weight loss, followed by darkening of the neck and the axillary regions. Physical examination disclosed a tumoral mass in the left flank and symmetrical, pigmented, velvety, verrucous plaques on both axillae, which is classical for AN. The diagnostic work-up disclosed a huge renal mass, which was resected and further diagnosed as a RCC. The post-operative period was uneventful and the skin alteration was evanescent at the first follow-up consultation. The authors call attention to the association of AN with RCC. PMID:27284539

  9. A case–control study of occupation/industry and renal cell carcinoma risk

    International Nuclear Information System (INIS)

    The role of occupation in the etiology of renal cell carcinoma (RCC) is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC). Between 2002 and 2007, a population-based case–control study of Caucasians and African Americans (1,217 cases; 1,235 controls) was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating occupation and industry to RCC risk using adjusted unconditional logistic regression models. Employment in the agricultural crop production industry for five years or more was associated with RCC (OR = 3.3 [95% CI = 1.0-11.5]) and ccRCC in particular (OR = 6.3 [95% CI = 1.7-23.3], P for trend with duration of employment = 0.0050). Similarly, RCC risk was elevated for employment of five years or longer in non-managerial agricultural and related occupations (ORRCC = 2.1 [95% CI = 1.0-4.5]; ORccRCC = 3.1 [95% CI = 1.4-6.8]). Employment in the dry-cleaning industry was also associated with elevated risk (ORRCC = 2.0 [95% CI = 0.9-4.4], P for trend = 0.093; ORccRCC = 3.0 [95% CI = 1.2-7.4], P for trend = 0.031). Suggestive elevated associations were observed for police/public safety workers, health care workers and technicians, and employment in the electronics, auto repair, and cleaning/janitorial services industries; protective associations were suggested for many white-collar jobs including computer science and administrative occupations as well employment in the business, legislative, and education industries. Our findings provide support for an elevated risk of RCC in the agricultural and dry-cleaning industries and suggest that these associations may be stronger for the ccRCC subtype. Additional studies are needed to confirm these

  10. Angiomotin promotes renal epithelial and carcinoma cell proliferation by retaining the nuclear YAP.

    Science.gov (United States)

    Lv, Meng; Li, Shuting; Luo, Changqin; Zhang, Xiaoman; Shen, Yanwei; Sui, Yan Xia; Wang, Fan; Wang, Xin; Yang, Jiao; Liu, Peijun; Yang, Jin

    2016-03-15

    Renal cell carcinoma (RCC) is one of the common tumors in the urinary system without effective therapies. Angiomotin (Amot) can interact with Yes-associated protein (YAP) to either stimulate or inhibit YAP activity, playing a potential role in cell proliferation. However, the role of Amot in regulating the proliferation of renal epithelial and RCC cells is unknown. Here, we show that Amot is expressed predominantly in the nucleus of RCC cells and tissues, and in the cytoplasm and nucleus of renal epithelial cells and paracancerous tissues. Furthermore, Amot silencing inhibited proliferation of HK-2 and 786-O cells while Amot upregulation promoted proliferation of ACHN cells. Interestingly, the location of Amot and YAP in RCC clinical samples and cells was similar. Amot interacted with YAP in HK-2 and 786-O cells, particularly in the nucleus. Moreover, Amot silencing mitigated the levels of nuclear YAP in HK-2 and 786-O cells and reduced YAP-related CTGF and Cyr61 expression in 786-O cells. Amot upregulation slightly increased the nuclear YAP and YAP-related gene expression in ACHN cells. Finally, enhanced YAP expression restored proliferation of Amot-silencing 786-O cells. Together, these data indicate that Amot is crucial for the maintenance of nuclear YAP to promote renal epithelial and RCC proliferation.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

  13. Primary extra-renal clear cell renal cell carcinoma masquerading as an adrenal mass: A diagnostic challenge

    Science.gov (United States)

    Hasan, Roumina; Kumar, Sandeep; Monappa, Vidya; Ayachit, Anurag

    2015-01-01

    We present the first case of a nonmetastasizing renal cell carcinoma (RCC) masquerading as an adrenal mass, in the presence of normal bilateral native kidneys, in a young adult. The possibility of this mass developing in a supernumerary kidney was ruled out, since no identifiable renal tissue, pelvis or ureters was seen within the mass, nor was any separate systemic arterial supply to the mass seen. The diagnosis of extra-renal clear cell RCC was based on cyto-morphological features, further confirmed by immunohistochemistry findings. The origin of this extra-renal clear cell renal cell is proposed to be from the mesodermal embryonic rests. PMID:26692677

  14. Contemporary approach to diagnosis and classification of renal cell carcinoma with mixed histologic features

    Institute of Scientific and Technical Information of China (English)

    Kanishka Sircar; Priya Rao; Eric Jonasch; Federico A.Monzon; Pheroze Tamboli

    2013-01-01

    Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide.Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease.Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical.RCC has been traditionally divided into clear-cell and non-clearcell categories,with papillary RCC forming the most common subtype of non-clear-cell RCC.Renal neoplasms with overlapping histologies,such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors,are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications.In this review,we discuss the histologic,immunohistochemical,cytogenetic,and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor's microscopic appearance and its molecular fingerprint.

  15. 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 include

  16. 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 include

  17. Outpatient-based subcutaneous interleukin-2 monotherapy in advanced renal cell carcinoma : An update

    NARCIS (Netherlands)

    Nieken, J; Sleijfer, DT; deLeij, L; Mulder, NH

    1996-01-01

    To minimize interleukin-2-related toxicity while retaining its efficacy, a treatment schedule utilizing subcutaneous IL-2 was evaluated in a phase II setting. Eighty unselected consecutive patients with metastatic or recurrent renal cell carcinoma (RCC), mean age 58 years (range, 21 to 76), received

  18. Renal cell carcinoma with vena caval tumor thrombus extending into the right atrium

    Institute of Scientific and Technical Information of China (English)

    JIANG Hai; ZHANG Zhi-gen; CHEN Zhao-dian; SHI Shi-fang; CAI Song-liang; WANG Shuo

    2006-01-01

    @@ The incidence of the inferior vena cava (IVC)tumor thrombus is reported to be 4%-10% in patients with renal cell carcinoma (RCC). Tumor thrombus may extend through to the right atrium.Management of patients with level Ⅲ/Ⅳ tumor thrombus is usually difficult. We report two cases of level Ⅳ thrombus in our hospital in 2002 and 2004.

  19. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    Directory of Open Access Journals (Sweden)

    Kucuk Omer

    2007-01-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion Our studies in both RCC and prostate tumor models demonstrate that the

  20. Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    Sugiyama Takayuki

    2011-07-01

    Full Text Available Abstract Background Improving the treatment of renal cell carcinoma (RCC will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7, also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC, overexpress FABP7. The abundant expression of FABP7 in primary RCCs compared to certain RCC-derived cell lines may allow the definition of the molecular components of FABP7's regulatory system. Results We determined FABP7 mRNA levels in six RCC cell lines. Two were highly expressed, whereas the other and the embryonic kidney cell line (HEK293 were weakly expressed FABP7 transcripts. Western blot analysis of the cell lines detected strong FABP7 expression only in one RCC cell line. Promoter activity in the RCC cell lines was 3- to 21-fold higher than that of HEK293. Deletion analysis demonstrated that three FABP7 promoter regions contributed to upregulated expression in RCC cell lines, but not in the HEK293 cell. Competition analysis of gel shifts indicated that OCT1, OCT6, and nuclear factor I (NFI bound to the FABP7 promoter region. Supershift experiments indicated that BRN2 (POU3F2 and NFI bound to the FABP7 promoter region as well. There was an inverse correlation between FABP7 promoter activity and BRN2 mRNA expression. The FABP7-positive cell line's NFI-DNA complex migrated faster than in other cell lines. Levels of NFIA mRNA were higher in the HEK293 cell line than in any of the six RCC cell lines. In contrast, NFIC mRNA expression was lower in the HEK293 cell line than in the six RCC cell lines. Conclusions Three putative FABP7 promoter regions drive reporter gene expression in RCC cell lines, but not in the HEK293 cell line. BRN2 and NFI may be key

  1. 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

    therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... the major advances in the characterization and application of TIL therapy for patients with RCC and OC....... 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...

  2. ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-08-01

    Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

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

    OpenAIRE

    Park, Min Jee; Baek, Hae Woon; Rhee, Ye-Young; Lee, Cheol; Park, Jeong Whan; Kim, Hwal Woong; Moon, Kyung Chul

    2015-01-01

    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 ...

  4. Optimizing lutetium 177-anti-carbonic anhydrase IX radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model

    NARCIS (Netherlands)

    Muselaers, C.H.J.; Oosterwijk, E.; Bos, D.L.; Oyen, W.J.G.; Mulders, P.F.A.; Boerman, O.C.

    2014-01-01

    A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT st

  5. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    Science.gov (United States)

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

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

    Directory of Open Access Journals (Sweden)

    Clara E. Jäkel

    2012-01-01

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

  7. Renal-cell carcinomas in end-stage kidneys: a clinicopathological study with emphasis on clear-cell papillary renal-cell carcinoma and acquired cystic kidney disease-associated carcinoma.

    Science.gov (United States)

    Bhatnagar, Ramneesh; Alexiev, Borislav A

    2012-02-01

    Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases.

  8. Merkel Cell Carcinoma

    Science.gov (United States)

    ... of the Year Award Arnold P. Gold Foundation Humanism in Medicine Award Diversity Mentorship Program Eugene Van ... 300 PUVA treatments. What causes Merkel cell carcinoma? Scientists are still studying what causes this skin cancer. ...

  9. De Novo Renal Cell Carcinoma in a Kidney Allograft 20 Years after Transplant

    Directory of Open Access Journals (Sweden)

    Masataka Banshodani

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC in a kidney allograft is rare. We report the successful diagnosis and treatment of a de novo RCC in a nonfunctioning kidney transplant 20 years after engraftment. A 54-year-old man received a kidney transplant from his mother when he was 34 years old. After 10 years, chronic rejection resulted in graft failure, and the patient became hemodialysis-dependent. Intravenous contrast-enhanced computed tomography (CT for the evaluation of gastrointestinal symptoms revealed a solid 13 mm tumor in the kidney graft. The tumor was confirmed on ultrasound examination. This tumor had not been detected on a surveillance noncontrast CT scan. Needle biopsy showed that the tumor was an RCC. Allograft nephrectomy was performed. Pathological examination showed that the tumor was a Fuhrman Grade 2 RCC. XY-fluorescence hybridization analysis of the RCC showed that the tumor cells were of donor origin. One year after the surgery, the patient is alive and has no evidence of tumor recurrence. Regardless of whether a kidney transplant is functioning, it should periodically be imaged for RCC throughout the recipient’s lifetime. In our experience, ultrasonography or CT with intravenous contrast is better than CT without contrast for the detection of tumor in a nonfunctioning kidney transplant.

  10. [Merkel cell skin carcinoma].

    Science.gov (United States)

    Krejcí, K; Zadrazil, J; Tichý, T; Horák, P; Ciferská, H; Hodulová, M; Zezulová, M; Zlevorová, M

    2010-01-01

    Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun-exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one-third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high-risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin

  11. Targeted therapy for cytokine-refractory metastatic renal cell carcinoma, and treatment in the community.

    Science.gov (United States)

    Bukowski, Ronald M

    2006-05-01

    This report of a case of cytokine-refractory metastatic, clear-cell renal cell carcinoma (RCC) presents some current issues related to use of targeted therapy in the community. Due to the different mechanisms of cytostatic vs. cytotoxic agents, traditional response assessments may not always apply in deciding when to either continue or stop treatment. While community physicians may increasingly focus more on duration of response, symptom relief, and how well patients tolerate treatment, there is a clear need for validated surrogate markers of biologic activity and response, as well as randomized trials that directly compare some of the targeted therapies being applied in advanced RCC.

  12. RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma

    Science.gov (United States)

    Zhou, Dahai; Kannappan, Vinodh; Chen, Xiang; Li, Jingqin; Leng, Xuefeng; Zhang, Jinping; Xuan, Shiying

    2016-01-01

    Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target. PMID:27282106

  13. Tumor-associated macrophages are involved in tumor progression in papillary renal cell carcinoma.

    Science.gov (United States)

    Behnes, Carl Ludwig; Bremmer, Felix; Hemmerlein, Bernhard; Strauss, Arne; Ströbel, Philipp; Radzun, Heinz-Joachim

    2014-02-01

    Tumor-associated macrophages (TAMs) play a key role in cancer development. Especially, the immunosuppressive M2 phenotype is associated with increased tumor growth, invasiveness and metastasis. The differentiation of macrophages to the alternative phenotype M2 is mediated, inter alia, by macrophage colony-stimulating factor (M-CSF). Papillary renal cell carcinoma (RCC) represents a rare tumor type which, based upon histological criteria, can be subdivided into two subtypes (I and II), of which type II is associated with poor prognosis. In both subtypes, typically, a dense infiltrate of macrophages is found. In the present study, the expression of CD68, CD163, M-CSF, Ki-67, and CD31 was examined in 30 type I and 30 type II papillary RCCs (n = 60). Both types of papillary RCCs contained an equally dense infiltrate of CD68-positive macrophages. Nearly all macrophages in papillary RCC type II expressed CD163, a characteristic for M2 macrophages. In type I papillary RCC, less than 30 % of macrophages expressed CD163. Furthermore, tumor cells in type II papillary RCC expressed significantly more M-CSF and showed increased (Ki-67 expression defined) proliferative activity in comparison with type I papillary RCC. In addition, the (CD31 defined) capillary density was higher in type II than in type I papillary RCC. A dense infiltrate of M2 phenotype TAM and high M-CSF expression in tumor cells are key features of type II papillary RCC. These findings might explain why the prognosis of papillary RCC type II is worse than that of type I. PMID:24327306

  14. 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.

  15. AIF downregulation and its interaction with STK3 in renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Shengqiang Xu

    Full Text Available Apoptosis-inducing factor (AIF plays a crucial role in caspase-independent programmed cell death by triggering chromatin condensation and DNA fragmentation. Therefore, it might be involved in cell homeostasis and tumor development. In this study, we report significant AIF downregulation in the majority of renal cell carcinomas (RCC. In a group of RCC specimens, 84% (43 out of 51 had AIF downregulation by immunohistochemistry stain. Additional 10 kidney tumors, including an oxyphilic adenoma, also had significant AIF downregulation by Northern blot analysis. The mechanisms of the AIF downregulation included both AIF deletion and its promoter methylation. Forced expression of AIF in RCC cell lines induced massive apoptosis. Further analysis revealed that AIF interacted with STK3, a known regulator of apoptosis, and enhanced its phosphorylation at Thr180. These results suggest that AIF downregulation is a common event in kidney tumor development. AIF loss may lead to decreased STK3 activity, defective apoptosis and malignant transformation.

  16. Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential.

    Science.gov (United States)

    Sonke, Eric; Verrydt, Megan; Postenka, Carl O; Pardhan, Siddika; Willie, Chantalle J; Mazzola, Clarisse R; Hammers, Matthew D; Pluth, Michael D; Lobb, Ian; Power, Nicholas E; Chambers, Ann F; Leong, Hon S; Sener, Alp

    2015-09-15

    Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism and angiogenesis. Using the H2S-specific probe MeRhoAz, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism and survival of ccRCC cell lines, as determined by live-cell imaging, XTT/ATP assay, and flow cytometry respectively. Using the chorioallantoic membrane angiogenesis model, it was found that systemic inhibition of endogenous H2S production was able to decrease vascularization of VHL-deficient ccRCC xenografts. Endogenous H2S production is an attractive new target in ccRCC due to its involvement in multiple aspects of disease.

  17. Tivozanib in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hepgur M

    2013-06-01

    Full Text Available Mehmet Hepgur, Sarmad Sadeghi, Tanya B Dorff, David I Quinn Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA Abstract: Renal cell carcinoma (RCC is an aggressive malignancy compared to other urological malignancies and has been associated with poor responses to conventional cytotoxic chemotherapy. Interferon-a and interleukin-2 were previously utilized in a limited number of patients with good performance status due to toxicity and safety issues. Over the last decade, through advances in the understanding of the biology and pathology of RCC, the important role of vascular endothelial growth factor (VEGF in RCC has been identified. Data from randomized trials have led to the approval of first-generation tyrosine kinase inhibitors (TKIs sorafenib, sunitinib, and pazopanib; however, these agents inhibit a wide variety of kinase targets and are associated with a range of adverse effects. More recently, a new generation TKI, axitinib, has been approved by the US Food and Drug Administration. Tivozanib is a novel TKI, which is a potent inhibitor of VEGF-1, VEGF-2, VEGF-3, c-kit, and PDGR kinases, with a more restricted target spectrum. Phase II and III studies have demonstrated significant activity and a favorable safety profile as an initial targeted treatment for advanced RCC. This review examines the emerging data with tivozanib for the treatment of advanced RCC. Preclinical investigations as well as Phase I, II, and III data are examined; data on the comparative benefits of tivozanib are reviewed. Finally, we discuss the future potential of tivozanib in combination, biomarkers associated with tivozanib response, and acquisition of resistance and nonkidney cancer indications. Keywords: targeted therapy, renal cell cancer, tyrosine kinase inhibitor, tivozanib

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

    Energy Technology Data Exchange (ETDEWEB)

    Redova, Martina; Svoboda, Marek [Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno (Czech Republic); Slaby, Ondrej, E-mail: slaby@mou.cz [Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno (Czech Republic); Central European Institute of Technology, Masaryk University, Brno (Czech Republic)

    2011-02-11

    Research highlights: {yields} MiRNAs are related to the processes of cell proliferation, apoptosis, angiogenesis, invasion, and metastasis in RCC. {yields} MiRNAs expression profiles are associated with several RCC-specific genetic alterations. {yields} It has been well documented that several miRNAs are downstream effector molecules of the HIF-induced hypoxia response. {yields} MiR-200 family is linked to epithelial-mesenchymal transition which is one of the most significant pathogenetic mechanism in RCC. {yields} 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.

  19. Metastatic clear cell renal carcinoma - an unusual response to Temsirolimus in second line therapy.

    Science.gov (United States)

    Stanculeanu, D L; Lazescu, A; Zob, D D; Bunghez, R; Anghel, R; Poteca, T D

    2016-01-01

    Renal cell carcinoma (RCC) represents 3% of all cancers, with the highest incidence occurring in the most developed countries and representing the seventh most common cancer in men and the ninth most common cancer in women. The understanding of the tumor molecular biology and the discovery of new drugs that target molecular pathways have increased the arsenal against advanced renal cell carcinoma and improved the outcomes in the patients suffering from these affections. Studying the molecular signaling that controls the tumor growth and the progression has led to the development of molecular therapies targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways, resulting in a significant improvement in the overall survival and quality of life. Sunitinib represents an inhibitor of VEGFR 1-3, c-kit, FLT-3 and PDGFR. We present the case of a patient with metastatic clear cell RCC with a treatment effect following sequential VEGF and mTOR inhibitor treatment. Under sunitinib treatment, the patient had a progression free survival (PFS) of approximately 9 months, similar to the PFS observed in clinical trials. Sunitinib was well tolerated by this patient. Temsirolimus, an mTOR inhibitor, is currently only approved for the first-line treatment of mRCC patients with poor prognosis. This study analyzes a treatment effect of second line temsirolimus in a patient with metastatic renal cell carcinoma (mRCC). PMID:27453754

  20. Fine mapping of the 1q21 breakpoint of the papillary venal cell carcinoma-associated (X;1) translocation

    NARCIS (Netherlands)

    Weterman, MAJ; Dijkhuizen, T; vandenBerg, E; vanKessel, AG

    1996-01-01

    A combination of Southern blot analysis on a panel of tumor-derived somatic cell hybrids and fluorescence in situ hybridization (FISH) techniques was used to map a series of DNA markers relative to the 1q21 breakpoint of the renal cell carcinoma (RCC)-associated (X;1)-(p11;q21) translocation. This b

  1. Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chao-Yuan [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Chu, Jan-Show [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Yang, Hsiu-Yuan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2012-08-01

    8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case–control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography with tandem mass spectrometry (LC–MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose–response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p = 0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC. -- Highlights: ► Urinary 8-OHdG was significantly related to urinary total arsenic. ► Higher urinary 8-OHdG was a strong predictor of RCC risk. ► Urinary 8-OHdG may modify arsenic related RCC risk.

  2. Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure

    International Nuclear Information System (INIS)

    8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case–control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography with tandem mass spectrometry (LC–MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose–response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p = 0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC. -- Highlights: ► Urinary 8-OHdG was significantly related to urinary total arsenic. ► Higher urinary 8-OHdG was a strong predictor of RCC risk. ► Urinary 8-OHdG may modify arsenic related RCC risk.

  3. Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma.

    Science.gov (United States)

    Bukowski, Ronald M

    2012-01-01

    Angiogenesis in general and the vascular endothelial growth factor (VEGF) signaling axis in particular is a validated target in renal cell carcinoma (RCC). Clear-cell carcinoma of the kidney is now recognized as a malignancy that is sensitive to inhibitors of the VEGF pathway. Treatment options for patients with metastatic renal cell carcinoma have evolved in dramatic fashion over the past 6 years, and a new paradigm has developed. The cytokines interferon-α and interleukin-2 were previously utilized for therapy, but since December 2005, six new agents have been approved in the United States for the treatment of advanced RCC. Two are tyrosine kinase inhibitors (TKI's) including sunitinib and recently pazopanib, and the multikinase inhibitor sorafenib. The current review examines the evolving data with the next generation of TKI's, axitinib and tivozanib being developed for the treatment of advanced RCC. These agents were synthesized to provide increased target specificity and enhanced target inhibition. The preclinical and clinical data are examined, an overview of the development of these TKI's is provided, and discussion plus speculation concerning their potential roles as RCC therapy is provided.

  4. Augmented telomerase activity, reduced telomere length and the presence of alternative lengthening of telomere in renal cell carcinoma: plausible predictive and diagnostic markers.

    Science.gov (United States)

    Pal, Deeksha; Sharma, Ujjawal; Khajuria, Ragini; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra

    2015-05-15

    In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase activity, telomere length and alternative lengthening of telomeres (ALT) using the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT associated promyelocytic leukemia (PML) bodies respectively. A significantly higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was correlated with clinicopathological features of tumor for instance, stage (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355). Notwithstanding, no correlation was found between telomerase activity and subtypes of RCC. Strikingly, the telomere length was found to be significantly shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes (P=0.669) of RCC. In this study, telomere length was also negatively correlated with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it could be used as a marker for biological aging. ALT associated PML bodies containing PML protein was found in telomerase negative cases of RCC. It suggests the presence of an ALT pathway mechanism to maintain the telomere length in telomerase negative RCC tissues which was associated with high stages of RCC, suggesting a prevalent mechanism for telomere maintenance in high stages. In conclusion, the telomerase activity and telomere length can be used as a diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism in high stages of RCC is warranted for the development of anti-ALT inhibitors along with telomerase inhibitor against RCC as a therapeutic approach. PMID:25769384

  5. The clinical and biological significance of MICA in clear cell renal cell carcinoma patients.

    Science.gov (United States)

    Zhang, Xiang; Yan, Lei; Jiao, Wei; Ren, Juchao; Xing, Naidong; Zhang, Yongzhen; Zang, Yuanwei; Wang, Jue; Xu, Zhonghua

    2016-02-01

    Major histocompatibility complex class I-related chains A (MICA), a ligand of Natural killer group 2, member D (NKG2D) receptor, is broadly upregulated in epithelial originated tumor cells. MICA plays a critical role in the immune surveillance against tumor cells and is associated with the prognosis of several malignancies. The aim of this study is to evaluate the clinical and biological significance of MICA in clear cell renal cell carcinoma (ccRCC). The expression of MICA was analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Both MICA mRNA and protein levels were upregulated in ccRCC tissues, compared with normal tissues. IHC staining revealed a homogenous pattern of MICA staining within each tumor, which combined both membrane staining and granular cytoplasmic staining. Furthermore, high MICA expression was associated with lymph node metastasis and advanced clinical stage and predicted poor prognosis in patients with ccRCC. Gene set enrichment analysis (GSEA) was performed using RNA-sequencing data from The Cancer Genome Atlas Research Network (TCGA) to elucidate the biological role of MICA in ccRCC and revealed that MICA was significantly associated with the epithelial-to-mesenchymal transition (EMT) gene set, which was further confirmed by qRT-PCR. Our findings contribute to the studies on biomarkers of kidney cancers and the mechanism of renal cancer progression driven by EMT pathway.

  6. Knockdown of COUP-TFII inhibits cell proliferation and induces apoptosis through upregulating BRCA1 in renal cell carcinoma cells.

    Science.gov (United States)

    Zheng, Jia; Qin, Weijun; Jiao, Dian; Ren, Jing; Wei, Ming; Shi, Shengjia; Xi, Wenjin; Wang, He; Yang, An-Gang; Huan, Yi; Wen, Weihong

    2016-10-01

    COUP-TFII belongs to the nuclear receptor family, which is highly expressed in many kinds of tumors. Previous studies have shown that COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cell proliferation and migration of certain cancer cells. However, the function of COUP-TFII in renal cell carcinoma (RCC) is not clear. Here, we showed that clinical RCC tumor tissues showed much higher COUP-TFII expression level than adjacent normal tissues. When COUP-TFII was knocked down in RCC 769-P and 786-O cells by siRNA or shRNA-expressing lentivirus, the cell proliferation was markedly inhibited, and apoptosis increased. Moreover, the tumor growth of COUP-TFII knockdown 769-P and 786-O xenografts in nude mice was also obviously inhibited. Using qRT-PCR and Western blot, we showed that the expression of the tumor suppressor gene BRCA1 was upregulated in COUP-TFII knockdown cells. Simultaneously knockdown of BRCA1 and COUP-TFII partially rescued the inhibited cell proliferation and increased apoptosis in COUP-TFII single knockdown cells. These results indicate that COUP-TFII may play an oncogenic role in RCC, and COUP-TFII may promote tumor progression through inhibiting BRCA1. PMID:27193872

  7. Suppression of PGC-1α is critical for reprogramming oxidative metabolism in renal cell carcinoma

    Science.gov (United States)

    LaGory, Edward L.; Wu, Colleen; Taniguchi, Cullen M.; Ding, Chien-Kuang Cornelia; Chi, Jen-Tsan; von Eyben, Rie; Scott, David A.; Richardson, Adam D.; Giaccia, Amato J.

    2015-01-01

    Summary Long believed to be a byproduct of malignant transformation, reprogramming of cellular metabolism is now recognized as a driving force in tumorigenesis. In clear cell renal cell carcinoma (ccRCC) frequent activation of HIF-signaling induces a metabolic switch that promotes tumorigenesis. Here we demonstrate that PGC-1α, a central regulator of energy metabolism, is suppressed in VHL-deficient ccRCC by a HIF/Dec1-dependent mechanism. In VHL wild type cells, PGC-1α suppression leads to decreased expression of the mitochondrial transcription factor Tfam and impaired mitochondrial respiration. Conversely, PGC-1α expression in VHL-deficient cells restores mitochondrial function and induces oxidative stress. ccRCC cells expressing PGC-1α exhibit impaired tumor growth and enhanced sensitivity to cytotoxic therapies. In patients, low levels of PGC-1α expression are associated with poor outcome. These studies demonstrate that suppression of PGC-1α recapitulates key metabolic phenotypes of ccRCC and highlight the potential of targeting PGC-1α expression as a therapeutic modality for the treatment of ccRCC. PMID:26119730

  8. Suppression of PGC-1α Is Critical for Reprogramming Oxidative Metabolism in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Edward L. LaGory

    2015-07-01

    Full Text Available Long believed to be a byproduct of malignant transformation, reprogramming of cellular metabolism is now recognized as a driving force in tumorigenesis. In clear cell renal cell carcinoma (ccRCC, frequent activation of HIF signaling induces a metabolic switch that promotes tumorigenesis. Here, we demonstrate that PGC-1α, a central regulator of energy metabolism, is suppressed in VHL-deficient ccRCC by a HIF/Dec1-dependent mechanism. In VHL wild-type cells, PGC-1α suppression leads to decreased expression of the mitochondrial transcription factor Tfam and impaired mitochondrial respiration. Conversely, PGC-1α expression in VHL-deficient cells restores mitochondrial function and induces oxidative stress. ccRCC cells expressing PGC-1α exhibit impaired tumor growth and enhanced sensitivity to cytotoxic therapies. In patients, low levels of PGC-1α expression are associated with poor outcome. These studies demonstrate that suppression of PGC-1α recapitulates key metabolic phenotypes of ccRCC and highlight the potential of targeting PGC-1α expression as a therapeutic modality for the treatment of ccRCC.

  9. Piperlongumine and its analogs down-regulate expression of c-Met in renal cell carcinoma.

    Science.gov (United States)

    Golovine, Konstantin; Makhov, Peter; Naito, Sei; Raiyani, Henish; Tomaszewski, Jeffrey; Mehrazin, Reza; Tulin, Alexei; Kutikov, Alexander; Uzzo, Robert G; Kolenko, Vladimir M

    2015-01-01

    The c-Met protein, a transmembrane receptor tyrosine kinase, is the product of a proto-oncogene. Its only known ligand, hepatocyte growth factor (HGF), regulates cell growth, motility, migration, invasion, proliferation, and angiogenesis. The aberrant expression of c-Met is often associated with poor prognosis in multiple cancers, including renal cell carcinoma (RCC). Silencing or inactivation of c-Met leads to decreased viability of cancer cells, thereby making ablation of c-Met signaling an attractive concept for developing novel strategies for the treatment of renal tumors. Naturally-occurring products or substances are the most consistent source of drug development. As such, we investigated the functional impact of piperlongumine (PL), a naturally occurring alkaloid present in the Long pepper (Piper longum) on c-Met expression in RCC cells and demonstrated that PL and its analogs rapidly reduce c-Met protein and RNA levels in RCC cells via ROS-dependent mechanism. PL-mediated c-Met depletion coincided with the inhibition of downstream c-Met signaling; namely Erk/MAPK, STAT3, NF-κB and Akt/mTOR. As such, PL and PL analogs hold promise as potential therapeutic agents for the treatment of metastatic RCC and the prevention of postoperative RCC recurrence. PMID:25801713

  10. Estramustine-binding protein (EMBP) in renal cell carcinoma immunohistochemistry, immunoscintigraphy and in vitro estramustine effects

    International Nuclear Information System (INIS)

    The present report shows that the human renal cell carcinoma (RCC) cell lines, A498 and CAKI-2, express the estramustine-binding protein (EMBP). The RCC cell lines investigated were highly sensitive for estramustine, with cell arrest in atypical metaphase. In vitro experiments using a fluorimetric cytotoxicity assay (FMCA) showed a pronounced cytotoxic effect mediate by estramustine. Immunohistochemical analysis of tumoru specimens from patients with RCC showed positive staining for EMBP in 12/16 cases. Immunoscintigraphy was performed in an experimental system in nude mice, heterotransplanted with the CAKI-2 cell line. A radiolabelled monoclonal anti-EMBP antibody was used. The results show a specific uptake of the antibody in the RCC tumour, expressed as a percentage of the injected dose per gram tissue, which ranged from 4.03 to 6.9. The results obtained from the basis for clinical studies on the feasibility of utilizing estramustine in the management of RCC. Immunoscintigraphy using the monoclonal anti-EMBP antibody is of potential use for in vivo characterization of the malignancy and in the selection patients suitable for treatment with estramustine. (orig.)

  11. Identification of genes associated with renal cell carcinoma using gene expression profiling analysis

    Science.gov (United States)

    YAO, TING; WANG, QINFU; ZHANG, WENYONG; BIAN, AIHONG; ZHANG, JINPING

    2016-01-01

    Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and accounts for ~80% of all kidney cancer cases. However, the pathogenesis of RCC has not yet been fully elucidated. To interpret the pathogenesis of RCC at the molecular level, gene expression data and bio-informatics methods were used to identify RCC associated genes. Gene expression data was downloaded from Gene Expression Omnibus (GEO) database and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in RCC patients compared with controls. In addition, a regulatory network was constructed using the known regulatory data between transcription factors (TFs) and target genes in the University of California Santa Cruz (UCSC) Genome Browser (http://genome.ucsc.edu) and the regulatory impact factor of each TF was calculated. A total of 258,0427 pairs of DCGs were identified. The regulatory network contained 1,525 pairs of regulatory associations between 126 TFs and 1,259 target genes and these genes were mainly enriched in cancer pathways, ErbB and MAPK. In the regulatory network, the 10 most strongly associated TFs were FOXC1, GATA3, ESR1, FOXL1, PATZ1, MYB, STAT5A, EGR2, EGR3 and PELP1. GATA3, ERG and MYB serve important roles in RCC while FOXC1, ESR1, FOXL1, PATZ1, STAT5A and PELP1 may be potential genes associated with RCC. In conclusion, the present study constructed a regulatory network and screened out several TFs that may be used as molecular biomarkers of RCC. However, future studies are needed to confirm the findings of the present study. PMID:27347102

  12. Predictive role of vascular endothelial growth factor polymorphisms in the survival of renal cell carcinoma patients.

    Science.gov (United States)

    Yang, Y-Q; Chen, J

    2014-01-01

    We conducted a study to investigate the possible role of the vascular endothelial growth factor (VEGF) polymorphisms -2578C/A, -1154G/A and -634C/G and clinical factors in renal cell carcinoma (RCC) prognosis in a cohort of 336 RCC cases. A total of 336 patients with RCC were recruited from PLA General Hospital between January 2004 and December 2005. All patients were followed up until December 2010, and no patient was lost to follow-up. The follow-up time of this study was 60 months. At the time of analysis, a total of 210 died during the follow-up. The median overall survival for patients was 29.1 months (95%CI = 17.1 to 41.3 months), and the 5-year survival rate for the patients was 37.5%. Our study showed that Karnofsky performance status ≥60 could delay death from RCC, with HR (95%CI) of 0.57 (0.39-0.84). Patients with anemia, platelet count >400 x 10(9)/L, neutrophilia and lymphocytes >160 g/L had increased risk of death from RCC, with HR (95%CI) of 1.84 (1.18-2.96), 2.01 (1.27-3.25), 1.65 (1.03-2.56) and 1.49 (0.99-2.71), respectively. The VEGF -2578AA and -1154AA genotypes were significantly associated with a poor overall survival of RCC patients, with HR (95%CI) of 2.41 (1.32-5.13) and 3.77 (1.42-15.67), respectively. In conclusion, our study presented the factors regarding the prognosis of RCC patients, and high platelet and neutrophil counts, low lymphocytes, and VEGF -2578C/A and -1154G/A polymorphisms were shown to be independent factors for a lower prognosis of RCC patients. PMID:25062489

  13. A case–control study of occupation/industry and renal cell carcinoma risk

    Directory of Open Access Journals (Sweden)

    Karami Sara

    2012-08-01

    Full Text Available Abstract Background The role of occupation in the etiology of renal cell carcinoma (RCC is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC. Methods Between 2002 and 2007, a population-based case–control study of Caucasians and African Americans (1,217 cases; 1,235 controls was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs and 95% confidence intervals (CIs relating occupation and industry to RCC risk using adjusted unconditional logistic regression models. Results Employment in the agricultural crop production industry for five years or more was associated with RCC (OR = 3.3 [95% CI = 1.0-11.5] and ccRCC in particular (OR = 6.3 [95% CI = 1.7-23.3], P for trend with duration of employment = 0.0050. Similarly, RCC risk was elevated for employment of five years or longer in non-managerial agricultural and related occupations (ORRCC = 2.1 [95% CI = 1.0-4.5]; ORccRCC = 3.1 [95% CI = 1.4-6.8]. Employment in the dry-cleaning industry was also associated with elevated risk (ORRCC = 2.0 [95% CI = 0.9-4.4], P for trend = 0.093; ORccRCC = 3.0 [95% CI = 1.2-7.4], P for trend = 0.031. Suggestive elevated associations were observed for police/public safety workers, health care workers and technicians, and employment in the electronics, auto repair, and cleaning/janitorial services industries; protective associations were suggested for many white-collar jobs including computer science and administrative occupations as well employment in the business, legislative, and education industries. Conclusions Our findings provide support for an elevated risk of RCC in the agricultural and dry-cleaning industries and

  14. Management of poor-risk metastatic renal cell carcinoma: current approaches, the role of temsirolimus and future directions.

    Science.gov (United States)

    Porta, Camillo; Tortora, Giampaolo; Larkin, James M G; Hutson, Thomas E

    2016-02-01

    Targeted therapies have substantially improved outcomes in metastatic renal cell carcinoma (mRCC). As expected, poor-risk patients have the worst outcomes. Temsirolimus is currently the only agent licensed for treatment of poor-risk mRCC patients. It is associated with meaningful improvements in survival and quality of life, highlighting the importance of correctly stratifying risk in mRCC patients so they receive optimal treatment. Currently, data for other targeted therapies in poor-risk patients are relatively sparse. Optimizing outcomes in these patients is the subject of ongoing research, including studies of biomarkers and studies to elucidate the role of nephrectomy and neoadjuvant targeted therapy in poor-risk mRCC patients. The impacts of novel combinations including temsirolimus have also been explored to further improve outcomes.

  15. Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma

    OpenAIRE

    Abe Hideyuki; Arai Kyoko; Tomosugi Naohisa; Kamai Takao; Yoshida Ken-Ichiro

    2009-01-01

    Abstract Background Hepcidin has an important role in iron metabolism. We investigated whether hepcidin was involved in renal cell carcinoma (RCC). Methods We measured serum hepcidin-25 levels in 32 patients by liquid chromatograpy (LC)-mass spectrometry (MS)/MS, and assessed hepcidin mRNA expression in paired tumor and non-tumor tissue samples from the surgical specimens of 53 consecutive patients with RCC by real-time reverse transcription polymerase chain reaction. Results The serum hepcid...

  16. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of 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.; Dragicevic, Dejan P.; Radic, Tanja M.; Bogdanovic, Ljiljana M.; Dzamic, Zoran M.; Pljesa-Ercegovac, Marija S.

    2016-01-01

    The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001, respectively). Furthermore, 22% of all recruited cRCC patients were carriers of combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as “risk-carrying genotype combination” in cRCC. PMID:27500405

  17. Treatment of Metastatic Renal Cell Carcinoma With CAIX CAR-engineered T cells : Clinical Evaluation and Management of On-target Toxicity

    NARCIS (Netherlands)

    Lamers, Cor H. J.; Sleijfer, Stefan; van Steenbergen, Sabine; van Elzakker, Pascal; van Krimpen, Brigitte; Groot, Corrien; Vulto, Arnold; den Bakker, Michael; Oosterwijk, Egbert; Debets, Reno; Gratama, Jan W.

    2013-01-01

    Autologous T cells genetically modified to express a chimeric antibody receptor (CAR) against carboxy-anhydrase-IX (CAIX) were administered to 12 patients with CAIX-expressing metastatic renal cell carcinoma (RCC). Patients were treated in three cohorts with a maximum of 10 infusions of a total of 0

  18. Piperlongumine and its analogs down-regulate expression of c-Met in renal cell carcinoma

    OpenAIRE

    Golovine, Konstantin; Makhov, Peter; Naito, Sei; Raiyani, Henish; Tomaszewski, Jeffrey; Mehrazin, Reza; Tulin, Alexei; Kutikov, Alexander; Uzzo, Robert G.; Kolenko, Vladimir M.

    2015-01-01

    The c-Met protein, a transmembrane receptor tyrosine kinase, is the product of a proto-oncogene. Its only known ligand, hepatocyte growth factor (HGF), regulates cell growth, motility, migration, invasion, proliferation, and angiogenesis. The aberrant expression of c-Met is often associated with poor prognosis in multiple cancers, including renal cell carcinoma (RCC). Silencing or inactivation of c-Met leads to decreased viability of cancer cells, thereby making ablation of c-Met signaling an...

  19. Anti-CD70 immunocytokines for exploitation of interferon-γ-induced RIP1-dependent necrosis in renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Peirong Chen

    Full Text Available Metastatic renal cell carcinoma (RCC is an incurable disease in clear need of new therapeutic interventions. In early-phase clinical trials, the cytokine IFN-γ showed promise as a biotherapeutic for advanced RCC, but subsequent trials were less promising. These trials, however, focused on the indirect immunomodulatory properties of IFN-γ, and its direct anti-tumor effects, including its ability to kill tumor cells, remains mostly unexploited. We have previously shown that IFN-γ induces RIP1 kinase-dependent necrosis in cells lacking NF-κB survival signaling. RCC cells display basally-elevated NF-κB activity, and inhibiting NF-κB in these cells, for example by using the small-molecule proteasome blocker bortezomib, sensitizes them to RIP1-dependent necrotic death following exposure to IFN-γ. While these observations suggest that IFN-γ-mediated direct tumoricidal activity will have therapeutic benefit in RCC, they cannot be effectively exploited unless IFN-γ is targeted to tumor cells in vivo. Here, we describe the generation and characterization of two novel 'immunocytokine' chimeric proteins, in which either human or murine IFN-γ is fused to an antibody targeting the putative metastatic RCC biomarker CD70. These immunocytokines display high levels of species-specific IFN-γ activity and selective binding to CD70 on human RCC cells. Importantly, the IFN-γ immunocytokines function as well as native IFN-γ in inducing RIP1-dependent necrosis in RCC cells, when deployed in the presence of bortezomib. These results provide a foundation for the in vivo exploitation of IFN-γ-driven tumoricidal activity in RCC.

  20. Recurrent Renal Cell Carcinoma with Synchronous Tumor Growth in Azygoesophageal Recess and Duodenum: A Rare Cause of Anemia and Upper Gastrointestinal Bleeding

    Science.gov (United States)

    Vootla, Vamshidhar R.; Kashif, Muhammad; Niazi, Masooma; Nayudu, Suresh K.

    2015-01-01

    Renal cell carcinoma (RCC) has potential to present with distant metastasis several years after complete resection. The common sites of metastases include the lungs, bones, liver, renal fossa, and brain. RCCs metastasize rarely to the duodenum, and duodenal metastasis presenting with acute gastrointestinal bleed is infrequently reported in literature. We present a case of synchronous presentation of duodenal and azygoesophageal metastasis manifesting as acute upper gastrointestinal bleeding, four years after undergoing nephrectomy for RCC. The patient underwent further workup and was treated with radiation. The synchronous presentation is rare and stresses the importance of searching for recurrence of RCC in patients presenting with acute gastrointestinal bleeding. PMID:26640732

  1. Involvement of multiple loci on chromosome 3 in renal cell cancer development

    NARCIS (Netherlands)

    van den Berg, Anke; Buys, CHCM

    1997-01-01

    In renal cell carcinoma (RCC), mostly occurring as sporadic cases, the short arm of chromosome 3 is a frequent target of deletion events. Taking into account cytological classifications of RCC, the deletions appear to be characteristic of clear cell or nonpapillary RCC only. This subtype constitutes

  2. Analysis of germline variants in CDH1, IGFBP3, MMP1, MMP3, STK15 and VEGF in familial and sporadic renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Christopher Ricketts

    Full Text Available BACKGROUND: The investigation of rare familial forms of kidney cancer has provided important insights into the biology of sporadic renal cell carcinoma (RCC. In particular, the identification of the von Hippel Lindau (VHL familial cancer syndrome gene (VHL provided the basis for the discovery that VHL is somatically inactivated in most sporadic clear cell RCC. Many cases of familial RCC do not have mutations in known RCC susceptibility genes and there is evidence that genetic modifiers may influence the risk of RCC in VHL disease patients. Hence we hypothesised that low-penetrance functional genetic variants in pathways related to the VHL protein (pVHL function might (a modify the phenotypic expression of VHL disease and/or (b predispose to sporadic RCC. METHODOLOGY/PRINCIPAL FINDINGS: We tested this hypothesis for functional polymorphisms in CDH1 (rs16260, IGFBP3 (rs2854744, MMP1 (rs1799750, MMP3 (rs679620, STK15 (rs2273535 and VEGF (rs1570360. We observed that variants of MMP1 and MMP3 were significant modifiers of RCC risk (and risks of retinal angioma and cerebellar haemangioblastoma in VHL disease patients. In addition, higher frequencies of the MMP1 rs1799750 2G allele (p = 0.017, OR 1.49, 95%CI 1.06-2.08 and the MMP1/MMP3 rs1799750/rs679620 2G/G haplotype (OR 1.45, 95%CI 1.01-2.10 were detected in sporadic RCC patients than in controls (n = 295. CONCLUSIONS/SIGNIFICANCE: These findings (a represent the first example of genetic modifiers of RCC risk in VHL disease, (b replicate a previous report of an association between MMP1/MMP3 variants and sporadic RCC and (c further implicate MMP1/MMP3-related pathways in the pathogenesis of familial and sporadic RCC.

  3. Basal Cell Carcinoma

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... cell carcinoma public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  4. Squamous Cell Carcinoma

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    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... cell carcinoma public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  5. The epigenetic modifier CHD5 functions as a novel tumor suppressor for renal cell carcinoma and is predominantly inactivated by promoter CpG methylation

    Science.gov (United States)

    Du, Zhenfang; Li, Lili; Huang, Xin; Jin, Jie; Huang, Suming; Zhang, Qian; Tao, Qian

    2016-01-01

    Renal cell carcinoma (RCC) is the most common urological cancer with steadily increasing incidence. A series of tumor suppressor genes (TSGs) have been identified methylated in RCC as potential epigenetic biomarkers. We identified a 1p36.3 TSG candidate CHD5 as a methylated target in RCC through epigenome study. As the role of CHD5 in RCC pathogenesis remains elusive, we further studied its expression and molecular functions in RCC cells. We found that CHD5 was broadly expressed in most normal genitourinary tissues including kidney, but frequently silenced or downregulated by promoter CpG methylation in 78% of RCC cell lines and 44% (24/55) of primary tumors. In addition, CHD5 mutations appear to be rare in RCC tumors through genome database mining. In methylated/silenced RCC cell lines, CHD5 expression could be restored with azacytidine demethylation treatment. Ectopic expression of CHD5 in RCC cells significantly inhibited their clonogenicity, migration and invasion. Moreover, we found that CHD5, as a chromatin remodeling factor, suppressed the expression of multiple targets including oncogenes (MYC, MDM2, STAT3, CCND1, YAP1), epigenetic master genes (Bmi-1, EZH2, JMJD2C), as well as epithelial-mesenchymal transition and stem cell markers (SNAI1, FN1, OCT4). Further chromatin immunoprecipitation (ChIP) assays confirmed the binding of CHD5 to target gene promoters. Thus, we demonstrate that CHD5 functions as a novel TSG for RCC, but is predominantly inactivated by promoter methylation in primary tumors. PMID:26943038

  6. Geographic Variation of Chronic Kidney Disease Prevalence: Correlation with the Incidence of Renal Cell Carcinoma or Urothelial Carcinoma?

    Directory of Open Access Journals (Sweden)

    Yit-Sheung Yap

    2015-01-01

    Full Text Available Background. The aim of this study is to evaluate whether geographic variations in the prevalence of late-stage chronic kidney disease (CKD exist and are associated with incidence rates of renal cell carcinoma (RCC, upper tract urothelial carcinoma (UTUC, or lower tract urothelial carcinoma (LTUC. Methods. Prevalence rates of late-stage CKD for 366 townships (n>30 in Taiwan were calculated for 1,518,241 and 1,645,151 subjects aged 40 years or older in years 2010 and 2009, respectively. Late-stage CKD prevalence in year 2010 was used as a training set and its age-adjusted standardized morbidity rates (ASMR were divided into three groups as defined <1.76%, 1.76% ≤ ASMR < 2.64%, and ≥2.64%, respectively. Year 2009, defined as the validation set, was used to validate the results. Results. The ASMR of late-stage CKD in years 2010 and 2009 were 1.76%, and 2.09%, respectively. Geographic variations were observed, with notably higher rates of disease in areas of the central, southwestern mountainside, and southeastern seaboard. There were no significant differences among different combined risk groups of RCC, UTUC, and LTUC incidence. Conclusion. The substantial geographic variations in the prevalence of late-stage CKD exist, but are not correlated with RCC, UTUC, or LTUC incidence.

  7. Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1

    Directory of Open Access Journals (Sweden)

    Zantl Niko

    2010-06-01

    Full Text Available Abstract Background Human renal cell carcinoma (RCC is very resistant to chemotherapy. ABT-737 is a novel inhibitor of anti-apoptotic proteins of the Bcl-2 family that has shown promise in various preclinical tumour models. Results We here report a strong over-additive pro-apoptotic effect of ABT-737 and etoposide, vinblastine or paclitaxel but not 5-fluorouracil in cell lines from human RCC. ABT-737 showed very little activity as a single agent but killed RCC cells potently when anti-apoptotic Mcl-1 or, unexpectedly, A1 was targeted by RNAi. This potent augmentation required endogenous Noxa protein since RNAi directed against Noxa but not against Bim or Puma reduced apoptosis induction by the combination of ABT-737 and etoposide or vinblastine. At the level of mitochondria, etoposide-treatment had a similar sensitizing activity and allowed for ABT-737-induced release of cytochrome c. Conclusions Chemotherapeutic drugs can overcome protection afforded by Mcl-1 and A1 through endogenous Noxa protein in RCC cells, and the combination of such drugs with ABT-737 may be a promising strategy in RCC. Strikingly, A1 emerged in RCC cell lines as a protein of similar importance as the well-established Mcl-1 in protection against apoptosis in these cells.

  8. Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma.

    Science.gov (United States)

    Yang, Shu-Mei; Huang, Chao-Yuan; Shiue, Horng-Sheng; Pu, Yeong-Shiau; Hsieh, Yi-Hsun; Chen, Wei-Jen; Lin, Ying-Chin; Hsueh, Yu-Mei

    2016-08-15

    Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR=0.38, 95% confidence interval (CI) 0.14-0.99]. Subjects with concurrent DNMT1 rs8101626 A/A+A/G and DNMT3A rs34048824 T/T+T/C genotypes had significantly higher OR for ccRCC [OR=2.88, 95% CI 1.44-5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. PMID:27292127

  9. Anti-Angiogenic Drugs in the Treatment of Metastatic Renal Cell Carcinoma:Advances in Clinical Application

    DEFF Research Database (Denmark)

    Nielsen, Ole H; Grimm, Daniela; Wehland, Markus;

    2014-01-01

    The current paradigm in attempting to treat metastatic renal cell carcinoma (mRCC) is a first line treatment with a vascular endothelial growth factor (VEGF) antagonist and second and subsequent treatments with either a vascular endothelial growth factor receptor (VEGFR) or a mTOR (mammalian Targ...

  10. Unusual Ultrasound Presentation of Testicular Metastasis from Renal Clear Cell Carcinoma

    Science.gov (United States)

    Dell’Atti, Lucio

    2016-01-01

    Testicular metastases from renal clear cell carcinoma (RCC) are extremely uncommon. To the best of our knowledge, only 32 cases have been reported in the literature. We report a rare case of testicular metastasis from RCC. A 69-year-old patient presented with discomfort and pain in his left testis. He had undergone laparoscopic left radical nephrectomy at another institution. Scrotal ultrasonography revealed a non-palpable lesion at the upper pole of the left testis with hypoechoic aspect, highly suspicious for malignancy. We performed a left inguinal orchiectomy. The testicular lesion was diagnosed as a metastasis from RCC. After orchiectomy, a computed tomography of the chest and abdomen revealed no other metastatic lesions. The patient remains free of clinical recurrence after 20 months without adjuvant therapy.

  11. Role of imaging in successful management of malignant ovarian vein thrombosis in RCC

    OpenAIRE

    Goyal, Ankur; Rangarajan, Krithika; Singh, Prabhjot; Das, Chandan Jyoti

    2014-01-01

    Renal cell carcinoma (RCC) is the most common renal malignancy in adults. Since complete surgical resection is the treatment of choice, accurate staging and extent delineation are imperative for optimal management. Owing to venous tropism, the tumour has a propensity to extend into renal vein and/or inferior vena cava. However, contiguous gonadal vein extension has rarely been reported. Here we present an unusual case of a 65-year-old woman who demonstrated a large left renal mass with extens...

  12. Chromophobe renal cell carcinoma of the kidney with neuroendocrine differentiation: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Ghadeer A Mokhtar

    2015-01-01

    Full Text Available Chromophobe renal cell carcinoma (chRCC is a distinctive type of malignant kidney tumor characterized by large cells with defined cell membrane. Primary renal neuroendocrine tumors (NET are rare with morphology similar to NET at other sites. There are few case reports describing the coexistence of these 2 neoplasms within the same tumor mass. We describe a case of chRCC with neuroendocrine features in a 70-year-old male patient who presented with hematuria and right flank pain. The histological and immunohistochemical features of both components were characteristic with no overlapping features. The neuroendocrine element was associated with nodal metastasis.

  13. Inhibitory Effect of Angiogenesis Inhibitor TNP-470 on Human ACHN Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    曾进; 梅伟; 黄海鹏; 李晓东; 孔鹏

    2002-01-01

    Summary: The contribution of angiogenesis inhibitor TNP-470 to the growth and metastasis ofACHN renal cell carcinoma (RCC) was studied. TNP-470 (40 mg/kg, every two days) was ad-ministrated to BABL/c nude mice bearing ACHN RCC. The mice were sacrificed after a treatmentduration of 31 days and the weight and volume of subcutaneous tumors as well as foci of lungmetastasis were measured. The microvascular density(MVD) of the tumor as well as the PCNAindex and apoptotic index of the tumor cells were evaluated immunohistochemically. Resultshowed that the growth of ACHN RCC was suppressed significantly and none metastasis was ob-served in TNP-470-treated mice. Compared with the control group, the MVD was decreasedmarkedly (P<0. 01) and the apoptotic index was increased significantly (P<0. 01) in the treatedgroup. The tumor volume was positively correlated to the MVD (r=0. 7144, P<0. 01) and in-versely correlated to the apoptotic index (r=-0. 8607, P<0. 01), and MVD was conversely cor-related to the apoptotic index. It was determined that TNP-470 could effectively inhibit angiogene-sis of ACHN RCC, which resulting in ischemia and hypoxia, leading to increased apoptosis, thusobviously suppressing the growth and metastasis of ACHN RCC in nude mice.

  14. p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma

    Science.gov (United States)

    Sánchez-Prieto, Ricardo; Saada, Sofiane; Naves, Thomas; Guillaudeau, Angélique; Perraud, Aurélie; Sindou, Philippe; Lacroix, Aurélie; Descazeaud, Aurélien; Lalloué, Fabrice; Jauberteau, Marie-Odile

    2016-01-01

    p75NTR, a member of TNF receptor family, is the low affinity receptor common to several mature neurotrophins and the high affinity receptor for pro-neurotrophins. Brain-Derived Neurotrophic Factor (BDNF), a member of neurotrophin family has been described to play an important role in development and progression of several cancers, through its binding to a high affinity tyrosine kinase receptor B (TrkB) and/or p75NTR. However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated. An overexpression of p75NTR, pro-BDNF, and to a lesser extent for TrkB and sortilin, was detected by immunohistochemistry in a cohort of 83 clear cell RCC tumors. p75NTR, mainly expressed in tumor tissues, was significantly associated with higher Fuhrman grade in multivariate analysis. In two derived-RCC lines, 786-O and ACHN cells, we demonstrated that pro-BDNF induced cell survival and migration, through p75NTR as provided by p75NTR RNA silencing or blocking anti-p75NTR antibody. This mechanism is independent of TrkB activation as demonstrated by k252a, a tyrosine kinase inhibitor for Trk neurotrophin receptors. Taken together, these data highlight for the first time an important role for p75NTR in renal cancer and indicate a putative novel target therapy in RCC. PMID:27120782

  15. Nasal metastases from renal cell carcinoma are associated with Memorial Sloan-Kettering Cancer Center poor-prognosis classification

    Institute of Scientific and Technical Information of China (English)

    Caroline Victoria Choong; Tiffany Tang; Wen Yee Chay; Christopher Goh; Miah Hiang Tay; Nor Azhari Mohd Zam; Puay Hoon Tan; Min-Han Tan

    2011-01-01

    Unusual sites of metastases are recognized in patients with renai cell carcinoma (RCC). However, the prognostic implications of these sites are not well understood. We used the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification for metastatic RCC to evaluate 912 consecutive patients with RCC managed at the Singapore General Hospital between 1990 and 2009. Among these patients, 301 had metastases either at diagnosis or during the course of illness. Nasal metastases, all arising from clear cell RCC, were identified histologically in 4 patients (1.3% of those with metastasis). All 4 patients were classified as MSKCC poor prognosis by current risk criteria. Nasal metastases were significantly associated with lung and bone metastases. The frequency of nasal metastases in patients with metastatic RCC is about 1%, occurring predominantly in patients with clear cell RCC. Nasal metastases are associated with poor prognosis as estimated by the MSKCC risk classification, with attendant implications for selection of targeted therapy, and are usually associated with multi-organ dissemination, including concurrent lung and bone involvement.

  16. Peroxisome proliferator-activated receptor γ ligands induce cell cycle arrest and apoptosis in human renal carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Feng-guang YANG; Zhi-wen ZHANG; Dian-qi XIN; Chang-jin SHI; Jie-ping WU; Ying-lu GUO; You-fei GUAN

    2005-01-01

    Aim: To study the effect of peroxisome proliferator-actived receptor γ (PPARγ)ligands on cell proliferation and apoptosis in human renal carcinoma cell lines.Methods: The expression of PPARγ was investigated by reverse transcriptase polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry.The effect of thiazolidinedione (TZD) PPARγ ligands on growth of renal cell carcinoma (RCC) cells was measured by MTT assay and flow cytometric analysis. Cell death ELISA, Hoechst 33342 fluorescent staining and DNA ladder assay were used to observe the effects of PPARγ ligands on apoptosis. Regulatory proteins of cell cycle and apoptosis were detected by Western blot analysis. Results:PPARγ was expressed at much higher levels in renal tumors than in the normal kidney (2.16±0.85 vs 0.90±0.73; P<0.01 ). TZD PPARγ ligands inhibited RCC cell growth in a dose-dependent manner with IC50 values of 7.08 μmol/L and 11.32 μmol/L for pioglitazone, and 5.71 μmol/L and 8.38 μmol/L for troglitazone in 786-O and A498 cells, respectively. Cell cycle analysis showed a G0/G1 arrest in human RCC cells following 24-h exposure to TZD. Analysis of cell cycle regulatory proteins revealed that TZD decreased the protein levels of proliferating cell nuclear antigen, pRb, cyclin D1, and Cdk4 but increased the levels of p21 and p27 in a timedependent manner. Furthermore, high doses of TZD induced massive apoptosis in renal cancer cells, with increased Bax expression and decreased Bcl-2 expression.Conclusion: TZD PPARγ ligands showed potent inhibitory effect on proliferation,and could induce apoptosis in RCC cells. These results suggest that ligands for PPARγ have potential antitumor effects on renal carcinoma cells.

  17. The potential clinical value of FDG-PET for recurrent renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakatani, Koya, E-mail: koyakn@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-Ku, Kyoto 606-8507 Japan (Japan); Nakamoto, Yuji, E-mail: 9709.ynakamo1@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-Ku, Kyoto 606-8507 Japan (Japan); Saga, Tsuneo, E-mail: saga@nirs.go.jp [Department of Diagnostic Imaging Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-Ku, Chiba 263-8555 (Japan); Higashi, Tatsuya, E-mail: higashi@shigamed.jp [Research Institute, Shiga Medical Center for Adults, 5-4-30 Moriyama, Moriyama City, Shiga 524-8524 Japan (Japan); Togashi, Kaori, E-mail: ktogashi@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-Ku, Kyoto 606-8507 Japan (Japan)

    2011-07-15

    Purpose: The clinical value of positron emission tomography (PET) using {sup 18}F-fluorodeoxyglucose (FDG) for follow-up or suspected recurrence of renal cell carcinoma (RCC) has not been fully evaluated. The purpose of this study was to assess the diagnostic performance of FDG-PET for postoperative assessment in patients with RCC. Methods: We reviewed 28 scans in 23 patients who had undergone FDG-PET scans after surgery for RCC. Diagnostic accuracy of visually interpreted PET was evaluated based on final diagnoses obtained histologically or by clinical follow-up at least 6 months. Also, additional information over CT, influence on treatment decisions, and the accuracy of FDG uptake as a predictor of survival were assessed. Results: Recurrence of renal carcinoma was histologically (n = 15) or clinically (n = 6) confirmed in 21 of 28 cases. Overall, the sensitivity, specificity, and diagnostic accuracy using FDG-PET were 81%, 71%, and 79%, respectively. In papillary RCC, the sensitivity was 100%; however, that was 75% in clear cell RCC in patient-basis. PET correctly detected local recurrence and metastases in all cases in the peritoneum, bone, muscle and adrenal gland. Additional information was obtained from scans in 6 cases (21%), which influenced therapeutic management in 3 cases (11%). Cumulative survival rates over 5 years in the PET-positive vs. the PET-negative group were 46% vs. 83%, respectively (p = 0.17). Conclusions: FDG-PET would be useful for postoperative surveillance in patients with RCC, although its impact on treatment decisions may be limited. Further investigations are necessary to conclude whether PET has a prognostic value.

  18. SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer.

    Science.gov (United States)

    Cheng, Yingying; Wang, Xiaolin; Wang, Pingzhang; Li, Ting; Hu, Fengzhan; Liu, Qiang; Yang, Fan; Wang, Jun; Xu, Tao; Han, Wenling

    2016-07-01

    Sushi domain containing 2 (SUSD2) is type I membrane protein containing domains inherent to adhesion molecules. There have been few reported studies on SUSD2, and they have mainly focused on breast cancer, colon cancer, and HeLa cells. However, the expression and function of SUSD2 in other cancers remain unclear. In the present study, we conducted an integrated bioinformatics analysis based on the array data from the GEO database and found a significant downregulation of SUSD2 in renal cell carcinoma (RCC) and lung cancer. Western blotting and quantitative RT-PCR (qRT-PCR) confirmed that SUSD2 was frequently decreased in RCC and lung cancer tissues compared with the corresponding levels in normal adjacent tissues. The restoration of SUSD2 expression inhibited the proliferation and clonogenicity of RCC and lung cancer cells, whereas the knockdown of SUSD2 promoted A549 cell growth. Our findings suggested that SUSD2 functions as a tumor suppressor gene (TSG) in RCC and lung cancer. PMID:26815503

  19. Loss of VHL in RCC reduces repair and alters cellular response to benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Marten eSchults

    2013-10-01

    Full Text Available Mutations of the von Hippel-Lindau (VHL tumor suppressor gene occur in the majority of sporadic renal-cell carcinomas (RCC. Loss of VHL function is associated with stabilization of hypoxia-inducible factor α (HIFα. We and others demonstrated that there is a two-way interaction between the aryl hydrocarbon receptor, which is an important mediator in the metabolic activation and detoxification of carcinogens, and the HIF1-pathway leading to an increased genetic instability when both pathways are simultaneously activated. The aim of this study was to investigate how environmental carcinogens, such as benzo[a]pyrene (BaP, which can be metabolically activated to BaP-7,8-diOH-9,10-epoxide (BPDE play a role in the etiology of renal-cell carcinomas (RCC. We exposed VHL deficient RCC4 cells, in which HIFα is stabilized regardless of oxygen tension, to 0.1µM BaP for 18 hours. The mutagenic BPDE-DNA adduct levels were increased in HIFα stabilized cells. Using qRT-PCR, we demonstrated that absence of VHL significantly induced the mRNA levels of AhR downstream target CYP1A1. Furthermore, HPLC analysis indicated that loss of VHL increased the concentration of BaP-7,8-dihydroxydiol, the pre-cursor metabolite of BPDE. Interestingly, the capacity to repair BPDE-DNA adducts in the HIFα stabilized RCC4 cells, was markedly reduced. Taken together, these data indicate that loss of VHL affects BaP-mediated genotoxic responses in renal-cell carcinoma and decreases repair capacity.

  20. Nanotechnology combined therapy: tyrosine kinase-bound gold nanorod and laser thermal ablation produce a synergistic higher treatment response of renal cell carcinoma in animal model

    Science.gov (United States)

    Immunologically naïve nude mice (Athymic Nude-Foxn1nu) were injected bilaterally on the flanks (n=36) with 2.5 x 106 cells of a human metastatic renal cell carcinoma cell line (RCC 786-O). Subcutaneous xenograft tumors developed 1 cm palpable nodules. AuNR encapsulated in Human Serum Albumin (HSA) P...

  1. Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras.

    Science.gov (United States)

    Li, Pengxiang; Wong, Yu-Ning; Armstrong, Katrina; Haas, Naomi; Subedi, Prasun; Davis-Cerone, Margaret; Doshi, Jalpa A

    2016-02-01

    Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real-world setting. Utilizing the 2000-2010 SEER Research files, a pre-post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000-2005) and the targeted therapy era (2006-2010). RCC patients diagnosed in the targeted therapy era (N = 6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N = 7231, hazard ratio (HR) for all-cause death: 0.86, P < 0.01), while the change between the pre-post periods was not significant for advanced prostate cancer patients (HR: 0.97, P = 0.08). Advanced RCC patients had significantly larger improvements in overall survival compared to advanced prostate cancer patients (z = 4.31; P < 0.01). More detailed year-to-year analysis revealed greater survival improvements for RCC in the later years of the posttargeted period. Similar results were seen for cause-specific survival. Subgroup analyses by nephrectomy status, age, and gender showed consistent findings. Patients diagnosed with advanced RCC during the targeted therapy era had better survival outcomes than those diagnosed during the pretargeted therapy era. Future studies should examine the real-world survival improvements directly associated with targeted therapies. PMID:26645975

  2. Penis squamous cell carcinoma

    OpenAIRE

    Leonor Hernández Piñero; José Luis Rodríguez López; María de Lourdes Menéndez Villa

    2015-01-01

    Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagn...

  3. MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3

    International Nuclear Information System (INIS)

    Highlights: •miR-187 is down-regulated in clear cell renal cell carcinoma (ccRCC). •Down-regulation of miR-187 is associated with poor outcomes in patients with ccRCC. •miR-187 inhibits cell growth and migration though targeting B7-H3 in ccRCC. -- Abstract: Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we found that miR-187 was down-regulated in both tumor tissue and plasma of ccRCC patients. Lower miR-187 expression levels were associated with higher tumor grade and stage. All patients with high miR-187 expression survived 5 years, while with low miR-187 expression, only 42% survived. Suppressed in vitro proliferation, inhibited in vivo tumor growth, and decreased motility were observed in cells treated with the miR-187 expression vector. Further studies showed that B7 homolog 3 (B7-H3) is a direct target of miR-187. Over-expression of miR-187 decreased B7-H3 mRNA level and repressed B7-H3-3′-UTR reporter activity. Knockdown of B7-H3 using siRNA resulted in similar phenotype changes as that observed for overexpression of miR-187. Our data suggest that miR-187 is emerging as a novel player in the disease state of ccRCC. miR-187 plays a tumor suppressor role in ccRCC

  4. MicroRNA-187, down-regulated in clear cell renal cell carcinoma and associated with lower survival, inhibits cell growth and migration though targeting B7-H3

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jun [Foshan Maternal and Child Health Care Hospital, Foshan (China); Lei, Ting [Zhongshan People’s Hospital, Zhongshan (China); Xu, Congjie [Department of Urology, Pepole’s Hospital of Hainan Province, Haikou (China); Li, Huan; Ma, Wenmin; Yang, Yunxia; Fan, Shuming [Foshan Maternal and Child Health Care Hospital, Foshan (China); Liu, Yuchen, E-mail: s_ycliu1@stu.edu.cn [Anhui Medical University, Hefei (China)

    2013-08-23

    Highlights: •miR-187 is down-regulated in clear cell renal cell carcinoma (ccRCC). •Down-regulation of miR-187 is associated with poor outcomes in patients with ccRCC. •miR-187 inhibits cell growth and migration though targeting B7-H3 in ccRCC. -- Abstract: Aberrantly expressed microRNAs (miRNAs) are frequently associated with the aggressive malignant behavior of human cancers, including clear cell renal cell carcinoma (ccRCC). Based on the preliminary deep sequencing data, we hypothesized that miR-187 may play an important role in ccRCC development. In this study, we found that miR-187 was down-regulated in both tumor tissue and plasma of ccRCC patients. Lower miR-187 expression levels were associated with higher tumor grade and stage. All patients with high miR-187 expression survived 5 years, while with low miR-187 expression, only 42% survived. Suppressed in vitro proliferation, inhibited in vivo tumor growth, and decreased motility were observed in cells treated with the miR-187 expression vector. Further studies showed that B7 homolog 3 (B7-H3) is a direct target of miR-187. Over-expression of miR-187 decreased B7-H3 mRNA level and repressed B7-H3-3′-UTR reporter activity. Knockdown of B7-H3 using siRNA resulted in similar phenotype changes as that observed for overexpression of miR-187. Our data suggest that miR-187 is emerging as a novel player in the disease state of ccRCC. miR-187 plays a tumor suppressor role in ccRCC.

  5. Correlation analysis of VHL and Jade-1 gene expression in human renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Xiao-fen Wu

    2016-06-01

    Full Text Available The aim of this study was to investigate the correlation of von Hippel-Lindau tumor suppressor (VHL mRNA expression and jade family PHD finger 1 (Jade-1 gene expression in patients with renal cell carcinoma (RCC. Another aim of this study was to analyze the relationship of these two genes with clinicalpathological features of the RCC patients. Methods: A total of 75 RCC patients who received surgically therapy in our hospital were included. All patients had complete pathological data. The expression of VHL/Jade-1 was determined by real-time polymerase chain reaction (RT-PCR. Results: VHL and Jade-1 were both obviously downregulated in RCC tissues than that of the matched normal tissues, and both negatively correlated with tumor size as well as tumor grade. And we found a fine association of VHL gene expression with Jade-1. Conclusion: VHL/Jade-1 exhibited significantly decreased expression in RCC tissues and was closely related to the clinical prognosis of patients. The finding of VHL expression positively correlated with Jade-1 expression shed light and provided crucial evidence on the connection of VHL protein with Wnt/b-catenin pathway.

  6. Paclitaxel/Taxol sensitivity in human renal cell carcinoma is not determined by the p53 status.

    Science.gov (United States)

    Reinecke, Petra; Kalinski, Thomas; Mahotka, Csaba; Schmitz, Michael; Déjosez, Marion; Gabbert, Helmut Erich; Gerharz, Claus Dieter

    2005-05-26

    In this study, we analyzed the role of the p53 status for paclitaxel/Taxol sensitivity in renal cell carcinomas (RCCs) of the clear cell type. Using immunohistochemistry, nuclear p53 accumulation could not be correlated to the paclitaxel/Taxol sensitivity. DNA sequencing detected a p53 gene mutation in two out of eight RCC cell lines, i.e. in exon 8 (cell line clearCa-6), and in exon 9 (cell line clearCa-5). No correlation, however, was found between the p53 status of our RCC cell lines and their paclitaxel/Taxol sensitivity as indicated by the IC50 values. However, paclitaxel-induced growth inhibition in paclitaxel-sensitive RCC cell lines was accompanied by an increase in apoptosis, irrespective of their p53 status. Although CD95 up-regulation was observed in renal cell carcinoma with wild-type p53 upon paclitaxel treatment, paclitaxel-induced apoptosis itself is triggered independently from the CD95 system. In conclusion, the p53 status cannot predict paclitaxel/Taxol sensitivity in RCC cell lines of the clear cell type.

  7. 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.

  8. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab.

    Science.gov (United States)

    Bukowski, Ronald M

    2010-03-26

    The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC). One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.

  9. Impact of Gender in Renal Cell Carcinoma: The Relationship of FABP7 and BRN2 Expression with Overall Survival

    Science.gov (United States)

    Tan, Cheng; Takayama, Tatsuya; Takaoka, Naohisa; Fujita, Hiromi; Miyazaki, Miki; Sugiyama, Takayuki; Ozono, Seiichiro

    2014-01-01

    OBJECTIVE To investigate the relationship between gender differences in fatty acid-binding protein7 (FABP7) and BRN2 (POU class 3 homeobox 2) expression in renal cell carcinoma (RCC) and the prognosis of patients with RCC. MATERIALS AND METHODS immunohistochemical (IHC) staining as well as reverse transcription-polymerase chain reaction (RT-PCR) was performed in renal tissues from 103 patients (83 men, mean age = 63.6 years old; 20 women, mean age = 63.1 years old) underwent radical nephrectomy from January 1, 2001 through December 31, 2010. The probability of overall patient survival was estimated using the Kaplan-Meier method. RESULTS FABP7 mRNA expression was more frequent in men (P = 0.07) while BRN2 protein expression was significantly more frequent in women (P = 0.029). In particular, FABP7 was expressed in 100% of G1 renal cell carcinoma both in mRNA and protein levels. In women, FABP7 (−) and BRN2 (+) groups had a worse prognosis both in mRNA level (P = 0.038) and protein level (P = 0.058). BRN2 was expressed 100% of papillary RCC both in mRNA and protein levels. CONCLUSIONS Our results demonstrated that gender was a key factor in FABP7 and BRN2 expression in RCC, and the combination with FABP7 and BRN2 stratified by gender could be a new potential prognostic factor in patients with RCC. PMID:24653654

  10. Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line.

    Science.gov (United States)

    Khan, Mohammed I; Dębski, Konrad J; Dabrowski, Michał; Czarnecka, Anna M; Szczylik, Cezary

    2016-08-01

    In recent years, genome-wide RNA expression analysis has become a routine tool that offers a great opportunity to study and understand the key role of genes that contribute to carcinogenesis. Various microarray platforms and statistical approaches can be used to identify genes that might serve as prognostic biomarkers and be developed as antitumor therapies in the future. Metastatic renal cell carcinoma (mRCC) is a serious, life-threatening disease, and there are few treatment options for patients. In this study, we performed one-color microarray gene expression (4×44K) analysis of the mRCC cell line Caki-1 and the healthy kidney cell line ASE-5063. A total of 1,921 genes were differentially expressed in the Caki-1 cell line (1,023 upregulated and 898 downregulated). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) approaches were used to analyze the differential-expression data. The objective of this research was to identify complex biological changes that occur during metastatic development using Caki-1 as a model mRCC cell line. Our data suggest that there are multiple deregulated pathways associated with metastatic clear cell renal cell carcinoma (mccRCC), including integrin-linked kinase (ILK) signaling, leukocyte extravasation signaling, IGF-I signaling, CXCR4 signaling, and phosphoinositol 3-kinase/AKT/mammalian target of rapamycin signaling. The IPA upstream analysis predicted top transcriptional regulators that are either activated or inhibited, such as estrogen receptors, TP53, KDM5B, SPDEF, and CDKN1A. The GSEA approach was used to further confirm enriched pathway data following IPA. PMID:27279483

  11. Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line.

    Science.gov (United States)

    Khan, Mohammed I; Dębski, Konrad J; Dabrowski, Michał; Czarnecka, Anna M; Szczylik, Cezary

    2016-08-01

    In recent years, genome-wide RNA expression analysis has become a routine tool that offers a great opportunity to study and understand the key role of genes that contribute to carcinogenesis. Various microarray platforms and statistical approaches can be used to identify genes that might serve as prognostic biomarkers and be developed as antitumor therapies in the future. Metastatic renal cell carcinoma (mRCC) is a serious, life-threatening disease, and there are few treatment options for patients. In this study, we performed one-color microarray gene expression (4×44K) analysis of the mRCC cell line Caki-1 and the healthy kidney cell line ASE-5063. A total of 1,921 genes were differentially expressed in the Caki-1 cell line (1,023 upregulated and 898 downregulated). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) approaches were used to analyze the differential-expression data. The objective of this research was to identify complex biological changes that occur during metastatic development using Caki-1 as a model mRCC cell line. Our data suggest that there are multiple deregulated pathways associated with metastatic clear cell renal cell carcinoma (mccRCC), including integrin-linked kinase (ILK) signaling, leukocyte extravasation signaling, IGF-I signaling, CXCR4 signaling, and phosphoinositol 3-kinase/AKT/mammalian target of rapamycin signaling. The IPA upstream analysis predicted top transcriptional regulators that are either activated or inhibited, such as estrogen receptors, TP53, KDM5B, SPDEF, and CDKN1A. The GSEA approach was used to further confirm enriched pathway data following IPA.

  12. Renal Cell Carcinoma Metastasis from Biopsy Associated Hematoma Disruption during Robotic Partial Nephrectomy

    OpenAIRE

    Christopher Caputo; Ziho Lee; Andrew Harbin; Daniel Eun

    2014-01-01

    We describe a case in which a patient with a past medical history of ovarian cancer received a diagnostic renal biopsy for an incidentally discovered renal mass. During left robotic partial nephrectomy (RPN), a perinephric hematoma was encountered. The hematoma was not present on preoperative imaging and was likely a result of the renal biopsy. The renal cell carcinoma (RCC) and the associated hematoma were widely excised with negative surgical margins. On follow-up imaging at five months pos...

  13. 8-year survival in a patient with several recurrences of renal cell carcinoma after radical nephrectomy

    OpenAIRE

    Joshi, Shivam; Eldefrawy, Ahmed; Ciancio, Gaetano

    2012-01-01

    We describe the case of a patient with a large renal cell carcinoma (RCC) who underwent cytoreductive nephrectomy utilizing liver mobilization techniques similar to those used in transplantation. Despite recurrent metastases, our patient continues to survive eight years later with several metastasectomies and adjuvant chemotherapy. We report the case of a 48-year-old Hispanic American man who presented with a 4-month history of an enlarging right upper quadrant abdominal mass and hematuria. C...

  14. Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases

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    Chisato Ohe, MD

    2014-09-01

    Full Text Available Chromophobe renal cell carcinoma (ChRCC with neuroendocrine differentiation/morphology (NED/NEM is exceedingly rare. We present three cases of ChRCC with NED/NEM, two of which showed positivity for neuroendocrine markers on immunohistochemical analysis. Patients ranged in age from 49 to 79 years (mean: 64.3 years. One of the three patients died of metastatic disease to multiple organs. Of the remaining two patients, one is currently alive without disease and the other is alive with disease. Histologically, all three tumors were composed of conventional ChRCC and NEM showed glandular and rosette formation. Immunohistochemically, tumor cells were positive for CK7, KAI1, E-cadherin, and c-kit in both ChRCC and neuroendocrine areas in three cases. CD56 and synaptophysin immunoreactivity were detected in two cases; in only the neuroendocrine area in one case and in both components in the other. Neuroendocrine granules were ultrastructurally observed at both neuroendocrine and conventional areas of ChRCC. Array comparative genomic hybridization (CGH study indicated losses of chromosomes 1, 2, 6, 10, 17, 21, and Y in both conventional ChRCC and NED in one case. In addition, losses of chromosomes 1, 2, 4, 6, 9, 10, 13, 16p, 17, and 21 were observed in both components of the remaining one tumor. Furthermore, loss of chromosome 5 was identified only in the neuroendocrine area in this case. We concluded that the neuroendocrine area may reflect dedifferentiation within ChRCC. It is possible that losses of chromosomes 4, 5, and 16p may be involved in the neuroendocrine differentiation or progression of ChRCC.

  15. Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram

    Science.gov (United States)

    Gu, Liangyou; Ma, Xin; Li, Hongzhao; Chen, Luyao; Xie, Yongpeng; Zhao, Chaofei; Luo, Guoxiong; Zhang, Xu

    2016-01-01

    To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four markers using Kaplan-Meier method and Cox regression models. Additionally, a nomogram was established to predict the prognosis of sRCC patients. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), nevertheless, elevated LMR showed an adverse effect on reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50–11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a prognostic model including T stage, M stage, tumor necrosis and percentage of sarcomatoid generated a nomogram, which accurately predicted OS for sRCC patients. Preoperative NLR may serve as a potential prognostic biomarker in patients with sRCC and may help with clinical decisions about treatment intervention in clinical practice. The proposed nomogram can be used for the prediction of OS in patients with sRCC. PMID:27035802

  16. The Relationship of Expression of bcl-2, p53, and Proliferating Cell Nuclear Antigen (PCNA) to Cell Proliferation and Apoptosis in Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    朱朝辉; 邢诗安; 程平; 李国胜; 杨郁; 曾甫清; 鲁功成

    2004-01-01

    To investigate the relationship of bcl-2, p53, proliferating cell nuclear antigen (PCNA) to cell proliferation, apoptosis and pathological parameters, the patterns of cell growth and turnover in renal cell carcinoma (RCC), formalin-fixed and paraffin-embedded tissue blocks from 34 patients with RCC were examined. Cell proliferation activity was detected by PCNA immunostaining and the proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy- nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Expressions of bcl-2 and p53 were assessed immunohistochemically. Our results showed that the PI ranged from 6.0 % to 24.0 % (median 12.3 %) and theAI from 2.0 % to 8.0 % (median 5.4 %) in RCC. The expression of the bcl-2 protein was demonstrated in 15 cases (44.1 %); the expression of the p53 protein, however, was seen in only 3 case. bcl-2 positivity was not associated with PI or AI or any pathological parameters. There were close associations between PI and tumor grade and stage, and a significant relationship between AI and the tumor grade of RCC. Our study suggests that bcl-2 positivity was not associated with PI or AI or any pathological parameters. There are close associations between PI and AI and tumor grade and stage of RCC. Active cell proliferation may be accompanied by frequent apoptosis in RCC.

  17. Expression of methionine adenosyltransferase 2A in renal cell carcinomas and potential mechanism for kidney carcinogenesis

    International Nuclear Information System (INIS)

    Methionine adenosyltransferase 2A (MAT2A) is an enzyme that catalyzes the formation of S-adenosylmethionine (SAMe) by joining methionine and ATP. SAMe is a methyl donor for transmethylation and has an important role for DNA and/or protein methylation. MAT2A is expressed widely in many tissues especially in kidney. Several studies have demonstrated that there are abnormal expressions of MAT2A in several kinds of cancers such as liver and colon cancers. But the relationship of MAT2A between renal cell carcinomas (RCC) is less understood. The mRNA expression level of the MAT2A gene was determined in 24 RCC patients and 4 RCC cell lines, using real-time quantitative-polymerase chain reaction (RT-PCR). The MAT2A protein content was measured by western blotting and immunohistochemical analysis in 55 RCC patients. The mRNA levels of heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) were also analysized in patients using RT-PCR. The correlations between the MAT2A and HO-1 as well as COX-2 were analyzed with nonparametric Spearman method. MAT2A transcript was significantly downregulated in cancer tissues compared to normal tissues (P < 0.05). Immunohistochemical analysis and western blotting indicated that level of MAT2A protein was decreased in cancer tissues. The statistical analysis reveals a negative correlation between MAT2A and HO-1 expression in RCC patients and cell lines (P < 0.01). This study demonstrated that MAT2A was lower expression in cancer tissues, suggesting that it may be involved in the development of RCC. MAT2A is a transcriptional corepressor for HO-1 expression by supplying SAM for methyltransferases, which may be one of potential mechanism of MAT2A as tumor suppressor in kidney carcinogenesis

  18. The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

    International Nuclear Information System (INIS)

    Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG + GG genotype, in conjunction with high urinary total arsenic (≥ 14.02 μg/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg72Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area. -- Highlights: ► Subjects with p53 Pro/Pro or MDM2 GG genotype significantly increased RCC risk. ► A significant multiplicative joint effect of p53 and p21 on RCC risk. ► RCC patients with p53 Arg/Arg genotype had efficient arsenic methylation capacity. ► Joint effect of p53 or MDM2 genotype and high urinary total arsenic on RCC risk.

  19. Review : Third Generation Tyrosine Kinase Inhibitors and Their Development in Advanced Renal Cell Carcinoma

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    Ronald M Bukowski

    2012-02-01

    Full Text Available Angiogenesis in general and the VEGF signaling axis in particular is a validated target in renal cell carcinoma. Clear cell carcinoma of the kidney is now recognized as a malignancy that is sensitive to inhibitors of the vascular endothelial growth factor pathway. Treatment options for patients with metastatic renal cell carcinoma have evolved in dramatic fashion over the past six years, and a new paradigm has developed. The cytokines interferon-α and interleukin-2 were previously utilized for therapy, but since December 2005, six new agents have been approved in the United States for the treatment of advanced RCC. Three are tyrosine kinase inhibitors (TKI’s including sunitinib, sorafenib, and recently pazopanib. The current review examines the evolving data with the next generation of TKI’s, axitinib and tivozanib being developed for the treatment of advanced RCC. These agents were synthesized to provide increased target specificity and enhanced target inhibition. The preclinical and clinical data are examined, an overview of the development of these TKI’s is provided, and discussion plus speculation concerning their potential roles as RCC therapy is provided.

  20. Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma

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    Xue Yi-Jun

    2012-09-01

    Full Text Available Abstract Background Fork head box M1 (FoxM1 is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC. Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models. Methods Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed. Results FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P P = 0.01, distant metastasis (P = 0.01, TNM stage (P P = 0.003. The Kaplan–Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P P = 0.008. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2, MMP-9 and vascular endothelial growth factor (VEGF, resulting in the inhibition of migration, invasion, and angiogenesis. Conclusions These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a

  1. Vasoactive intestinal peptide (VIP) inhibits human renal cell carcinoma proliferation.

    Science.gov (United States)

    Vacas, Eva; Fernández-Martínez, Ana B; Bajo, Ana M; Sánchez-Chapado, Manuel; Schally, Andrew V; Prieto, Juan C; Carmena, María J

    2012-10-01

    Clear renal cell carcinoma (cRCC) is an aggressive and fatal neoplasm. The present work was undertaken to investigate the antiproliferative potential of vasoactive intestinal peptide (VIP) exposure on non-tumoral (HK2) and tumoral (A498, cRCC) human proximal tubular epithelial cell lines. Reverse transcription and semiquantitative PCR was used at the VIP mRNA level whereas enzyme immunoanalysis was performed at the protein level. Both renal cell lines expressed VIP as well as VIP/pituitary adenylate cyclase-activating peptide (VPAC) receptors whereas only HK2 cells expressed formyl peptide receptor-like 1 (FPRL-1). Receptors were functional, as shown by VIP stimulation of adenylyl cyclase activity. Treatment with 0.1μM VIP (24h) inhibited proliferation of A498 but not HK2 cells as based on a reduction in the incorporation of [(3)H]-thymidine and BrdU (5'-Br-2'-deoxyuridine), PCNA (proliferating-cell nuclear antigen) expression and STAT3 (signal transducer and activator of transcription 3) expression and activation. VPAC(1)-receptor participation was established using JV-1-53 antagonist and siRNA transfection. Growth-inhibitory response to VIP was related to the cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP (EPAC)/phosphoinositide 3-kinase (PI3-K) signaling systems as shown by studies on adenylate cyclase stimulation, and using the EPAC-specific compound 8CPT-2Me-cAMP and specific kinase inhibitors such as H89, wortmannin and PD98059. The efficacy of VIP on the prevention of tumor progression was confirmed in vivo using xenografted athymic mouse. These actions support a potential role of this peptide and its agonists in new therapies for cRCC.

  2. Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

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    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.

  3. Impact of Gender in Renal Cell Carcinoma: The Relationship of FABP7 and BRN2 Expression with Overall Survival

    OpenAIRE

    Cheng Tan; Tatsuya Takayama; Naohisa Takaoka; Hiromi Fujita; Miki Miyazaki; Takayuki Sugiyama; Seiichiro Ozono

    2014-01-01

    OBJECTIVE To investigate the relationship between gender differences in fatty acid-binding protein7 (FABP7) and BRN2 (POU class 3 homeobox 2) expression in renal cell carcinoma (RCC) and the prognosis of patients with RCC. MATERIALS AND METHODS immunohistochemical (IHC) staining as well as reverse transcription-polymerase chain reaction (RT-PCR) was performed in renal tissues from 103 patients (83 men, mean age = 63.6 years old; 20 women, mean age = 63.1 years old) underwent radical nephrecto...

  4. A novel method to identify pathways associated with renal cell carcinoma based on a gene co-expression network

    OpenAIRE

    Ruan, Xiyun; Li, Hongyun; Liu, Bo; Chen, Jie; ZHANG, SHIBAO; Sun, Zeqiang; LIU, SHUANGQING; SUN, FAHAI; Liu, Qingyong

    2015-01-01

    The aim of the present study was to develop a novel method for identifying pathways associated with renal cell carcinoma (RCC) based on a gene co-expression network. A framework was established where a co-expression network was derived from the database as well as various co-expression approaches. First, the backbone of the network based on differentially expressed (DE) genes between RCC patients and normal controls was constructed by the Search Tool for the Retrieval of Interacting Genes/Pro...

  5. Penis squamous cell carcinoma

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    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  6. Physapubescin selectively induces apoptosis in VHL-null renal cell carcinoma cells through down-regulation of HIF-2α and inhibits tumor growth.

    Science.gov (United States)

    Chen, Lixia; Xia, Guiyang; Qiu, Feng; Wu, Chunli; Denmon, Andria P; Zi, Xiaolin

    2016-01-01

    We have purified physapubescin, a predominant steroidal lactone, from medicinal plant Physalis pubescens L., commonly named as "hairy groundcherry" in English and "Deng-Long-Cao" in Chinese. Von Hippel-Lindau (VHL)-null 786-O, RCC4 and A498 Renal Cell Carcinoma (RCC) cell lines expressing high levels of Hypoxia Inducible Factor (HIF)-2α are more sensitive to physapubescin-mediated apoptosis and growth inhibitory effect than VHL wild-type Caki-2 and ACHN RCC cell lines. Restoration of VHL in RCC4 cells attenuated the growth inhibitory effect of physapubescin. Physapubescin decreases the expression of HIF-2α and increases the expression of CCAAT/enhancer-binding protein homologus protein (CHOP), which leads to up-regulation of death receptor 5 (DR5), activation of caspase-8 and -3, cleavage of poly (ADP-Ribose) polymerase (PARP) and apoptosis. Under hypoxia conditions, the apoptotic and growth inhibitory effects of physapubescin are further enhanced. Additionally, physapubescin synergizes with TNF-related apoptosis-inducing ligand (TRAIL) for markedly enhanced induction of apoptosis in VHL-null 786-O cells but not in VHL wild-type Caki-2 cells. Physapubescin significantly inhibited in vivo angiogenesis in the 786-O xenograft. Physapubescin as a novel agent for elimination of VHL-null RCC cells via apoptosis is warranted for further investigation. PMID:27581364

  7. Evaluation of anti-apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Garg Neeraj K; Mangal Sharad; Sahu Tejram; Mehta Abhinav; Vyas Suresh P; Tyagi Rajeev K

    2011-01-01

    Objective: To evaluate the anti-apoptotic and radical scavenging activities of dietary phenolics, namely ascorbic acid, -tocopherol acetate, citric acid, salicylic acid, and estimate H2O2-induced apoptosis in renal cell carcinoma cells. Methods: The intracellular antioxidant potency of antioxidants was investigated. H2O2-induced apoptosis in RCC-26 was assayed with the following parameters: cell viability (% apoptosis), nucleosomal damage and DNA fragmentation, bcl-2 levels and flow cytometery analysis (ROS production evaluation). Results: The anticancer properties of antioxidants such as ascorbic acid, - tocopherol acetate, citric acid, salicylic acid with perdurable responses were investigated. It was observed that these antioxidants had protective effect (anti-apoptotic activity) against hydrogen peroxide (H2O2) in renal cell carcinoma (RCC-26) cell line. Conclusions: This study reveals and proves the anticancer properties. However, in cancer cell lines anti-apoptotic activity can indirectly reflect the cancer promoter activity through radicals scavenging, and significantly protect nucleus and bcl-2.

  8. MicroRNA Expression Profiling in Clear Cell Renal Cell Carcinoma: Identification and Functional Validation of Key miRNAs.

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    Haowei He

    Full Text Available This study aims to profile dysregulated microRNA (miRNA expression in clear cell renal cell carcinoma (ccRCC and to identify key regulatory miRNAs in ccRCC.miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452 and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429 were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3' untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes.This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429 may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

  9. Targeted Therapy for Metastatic Renal Carcinoma: An Update

    OpenAIRE

    Rodrigo Donalisio da Silva; Diedra Gustafson; Leticia Nogueira; Werahera, Priya N.; Molina, Wilson R.; Kim, Fernando J.

    2014-01-01

    Conventional chemotherapy is associated with poor outcomes in metastatic renal cell carcinoma (RCC). Advances in the understanding of tumor molecular biology and the implementation of new drugs that target these molecular pathways have increased the arsenal against advanced RCC and improved outcomes in these patients. Herein, we briefly describe the latest data on targeted therapies used in the treatment of advanced renal cell carcinoma. Search strategy was performed according to PRISMA guide...

  10. Trisacryl Gelatin Microembolism and Metastases in the Lung after Renal Artery Embolization and Nephrectomy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Andres Borja Alvarez

    2015-01-01

    Full Text Available This is the first report, to our knowledge, of widespread, histologically confirmed trisacryl gelatin pulmonary microembolism after renal artery embolization (RAE. In addition, this is the first report of lung involvement by both metastatic renal cell carcinoma (RCC and an embolic agent used for RAE. The patient was a 63-year-old woman who recently presented with both dyspnea on exertion and productive cough. Her past medical history included clear cell RCC, which was treated with preoperative trisacryl gelatin microsphere RAE and right nephrectomy 9 years earlier. Computed tomography of the chest showed multiple lung nodules, a mass-like density in the left lower lobe, and mediastinal and hilar lymphadenopathy. Wedge resections of the lung showed multiple foci of metastatic RCC and extensive involvement of the muscular pulmonary arteries by trisacryl gelatin microspheres.

  11. Mucinous Tubular and Spindle Cell Carcinoma of the Kidney: A Case Report

    Science.gov (United States)

    Chrysikos, Dimosthenis; Zagouri, Flora; Sergentanis, Theodoros N.; Goutas, Nikolaos; Vlachodimitropoulos, Dimitrios; Flessas, Ioannis; Theodoropoulos, George; Lymperi, Maria; Birbas, Kostantinos; Zografos, George C.; Mariolis-Sapsakos, Theodoros

    2012-01-01

    Background Mucinous tubular and spindle cell carcinoma (MTSC) is a rare and newly described type of renal cell carcinoma (RCC) with relatively indolent behavior. Although there are small series of this clinical entity in the literature, its histogenetic origin or line of differentiation remains unclear. Patients and Methods A 67-year-old woman was hospitalized for flank pain; imaging studies revealed a 6.5-cm mass in the right kidney. She was referred for fine needle aspiration of the lesion, which showed an epithelial tumor with round to oval nuclei associated with strands of metachromatic stromal tissue. Cytopathologic diagnosis was consistent with RCC. Results Subsequent right heminephrectomy was performed and the surgical pathology specimen showed an MTSC of the kidney. The patient has done well postoperatively, with 24 months of benign follow-up. Conclusion A precise differential diagnosis between MTSC and other renal carcinomas (e.g. papillary RCC with sarcomatoid transformation) is important for predicting patient prognosis. Even though MTSC is a rare cause of renal masses, it should be included in the differential diagnosis, especially because its imaging might be misleading, mimicking other benign renal diseases. Heminephrectomy is the preferred treatment in these subjects. PMID:22807903

  12. Mucinous Tubular and Spindle Cell Carcinoma of the Kidney:A Case Report

    Directory of Open Access Journals (Sweden)

    Dimosthenis Chrysikos

    2012-07-01

    Full Text Available Background: Mucinous tubular and spindle cell carcinoma (MTSC is a rare and newly described type of renal cell carcinoma (RCC with relatively indolent behavior. Although there are small series of this clinical entity in the literature, its histogenetic origin or line of differentiation remains unclear. Patients and Methods: A 67-year-old woman was hospitalized for flank pain; imaging studies revealed a 6.5-cm mass in the right kidney. She was referred for fine needle aspiration of the lesion, which showed an epithelial tumor with round to oval nuclei associated with strands of metachromatic stromal tissue. Cytopathologic diagnosis was consistent with RCC. Results: Subsequent right heminephrectomy was performed and the surgical pathology specimen showed an MTSC of the kidney. The patient has done well postoperatively, with 24 months of benign follow-up. Conclusion: A precise differential diagnosis between MTSC and other renal carcinomas (e.g. papillary RCC with sarcomatoid transformation is important for predicting patient prognosis. Even though MTSC is a rare cause of renal masses, it should be included in the differential diagnosis, especially because its imaging might be misleading, mimicking other benign renal diseases. Heminephrectomy is the preferred treatment in these subjects.

  13. Collecting Duct Renal Cell Carcinoma Found to Involve the Collecting System During Partial Nephrectomy: A Case Report

    Directory of Open Access Journals (Sweden)

    Andrew C Harbin

    2015-06-01

    Full Text Available Collecting duct carcinoma (CDC is a rare and aggressive form of renal cell carcinoma (RCC arising from the principal cells of the collecting duct.  One third of cases present with metastatic disease, but many present in a manner similar to conventional RCC or urothelial carcinoma (UC.  We discuss a case of CDC which presented as a small mass at the cortico-medullary junction, and was discovered at robotic partial nephrectomy (RPN to be grossly involving the collecting system. A 62-year-old man presented with a small renal mass suspicious for RCC, which was found on computed tomography (CT after an episode of gross hematuria.  After thorough workup, RPN was attempted; however, intraoperatively the mass was found to be involving the collecting system.  Radical nephroureterectomy was performed, and the pathology report revealed CDC.  CDC is a rare and aggressive form of RCC.  While many cases are metastatic at diagnosis, most patients present with the incidental finding of a small renal mass.  There are no reports of a CDC involving the collecting system at RPN after negative ureteroscopy preoperatively.  The adjuvant therapeutic options for CDC are limited, and long term survival is poor.    

  14. Optimized Temporal Window for Detection and Characterization of Renal Cell Carcinomas with Dynamic CT Scanning

    Institute of Scientific and Technical Information of China (English)

    Jinhong Wang; Peijun Wang; Xiaohu Zhao; Xinqin Mao; Xiaolong Gao; Jun Liu

    2005-01-01

    OBJECTIVE To investigate the optimized time period for detection and characterization of renal cell carcinomas (RCC) when the specific CT features appear during spiral dynamic CT scanning, and to optimize an effective scanning protocol of spiral CT for evaluating RCC.METHODS Twenty-four patients with RCC verified by pathology had undergone a dynamic CT (D-CT) scan. A plain scan was employed to select the target slice. Single-level dynamic scanning started at 14-17 s after the intravenous contrast media had been administered, with a scan interval of 4.9 s acquiring a total number of 17~24 frames. A regular CT scan of the whole kidney followed by a delayed single slice acquisition through the target slice in the excretory phase was performed. Images were assessed in two ways: (1) A group of experienced radiologists reviewed the CT images to find when the specific signs appeared and when the CT features of RCC were optimally displayed; (2) Data measurement of the time-density curves (T-DC) of RCC. The exact time was obtained when the densities of the tumor, renal parenchyma, medulla and aorta reached their peak enhancement, thus also the time when the density difference between tumor and parenchyma was at maximum (Max T-M). Based on the slope of the contrast media uptake curve, T-DC types were ranked from the smallest to the biggest of slope as type A, B and C.RESULTS 1. The review of the CT images by the radiologists showed that the CT features of RCC were optimally demonstrated at 70.2 s. The earliest time at which RCC CT features were examined was at 23.9 s. 2. Image data analysis: the time that the density (or CT value) of the tumor mass reached peak enhancement was at 54 s and peak value was at 80.4 Hu for RCC. The time of the maximal difference of densities between tumor and renal parenchyma was at 102 s.CONCLUSION The following proposal is the scanning protocol for detecting RCC recommended by our research: After a plain scan to determine the target level, a

  15. Automated grading of renal cell carcinoma using whole slide imaging

    Directory of Open Access Journals (Sweden)

    Fang-Cheng Yeh

    2014-01-01

    Full Text Available Introduction: Recent technology developments have demonstrated the benefit of using whole slide imaging (WSI in computer-aided diagnosis. In this paper, we explore the feasibility of using automatic WSI analysis to assist grading of clear cell renal cell carcinoma (RCC, which is a manual task traditionally performed by pathologists. Materials and Methods: Automatic WSI analysis was applied to 39 hematoxylin and eosin-stained digitized slides of clear cell RCC with varying grades. Kernel regression was used to estimate the spatial distribution of nuclear size across the entire slides. The analysis results were correlated with Fuhrman nuclear grades determined by pathologists. Results: The spatial distribution of nuclear size provided a panoramic view of the tissue sections. The distribution images facilitated locating regions of interest, such as high-grade regions and areas with necrosis. The statistical analysis showed that the maximum nuclear size was significantly different (P < 0.001 between low-grade (Grades I and II and high-grade tumors (Grades III and IV. The receiver operating characteristics analysis showed that the maximum nuclear size distinguished high-grade and low-grade tumors with a false positive rate of 0.2 and a true positive rate of 1.0. The area under the curve is 0.97. Conclusion: The automatic WSI analysis allows pathologists to see the spatial distribution of nuclei size inside the tumors. The maximum nuclear size can also be used to differentiate low-grade and high-grade clear cell RCC with good sensitivity and specificity. These data suggest that automatic WSI analysis may facilitate pathologic grading of renal tumors and reduce variability encountered with manual grading.

  16. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma.

    Science.gov (United States)

    Lucarelli, Giuseppe; Galleggiante, Vanessa; Rutigliano, Monica; Sanguedolce, Francesca; Cagiano, Simona; Bufo, Pantaleo; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Domenico; Giglio, Andrea; Serino, Grazia; Vavallo, Antonio; Bettocchi, Carlo; Selvaggi, Francesco Paolo; Battaglia, Michele; Ditonno, Pasquale

    2015-05-30

    The analysis of cancer metabolome has shown that proliferating tumor cells require a large quantities of different nutrients in order to support their high rate of proliferation. In this study we analyzed the metabolic profile of glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell proliferation, maintenance of NADPH levels, and production of reactive oxygen species (ROS). Metabolomic analysis showed a clear signature of increased glucose uptake and utilization in ccRCC tumor samples. Elevated levels of glucose-6-phosphate dehydrogenase (G6PDH) in association with higher levels of PPP-derived metabolites, suggested a prominent role of this pathway in RCC-associated metabolic alterations. G6PDH inhibition, caused a significant decrease in cancer cell survival, a decrease in NADPH levels, and an increased production of ROS, suggesting that the PPP plays an important role in the regulation of ccRCC redox homeostasis. Patients with high levels of glycolytic enzymes had reduced progression-free and cancer-specific survivals as compared to subjects with low levels. Our data suggest that oncogenic signaling pathways may promote ccRCC through rerouting the sugar metabolism. Blocking the flux through this pathway may serve as a novel therapeutic target. PMID:25945836

  17. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma.

    Science.gov (United States)

    Lucarelli, Giuseppe; Galleggiante, Vanessa; Rutigliano, Monica; Sanguedolce, Francesca; Cagiano, Simona; Bufo, Pantaleo; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Domenico; Giglio, Andrea; Serino, Grazia; Vavallo, Antonio; Bettocchi, Carlo; Selvaggi, Francesco Paolo; Battaglia, Michele; Ditonno, Pasquale

    2015-05-30

    The analysis of cancer metabolome has shown that proliferating tumor cells require a large quantities of different nutrients in order to support their high rate of proliferation. In this study we analyzed the metabolic profile of glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell proliferation, maintenance of NADPH levels, and production of reactive oxygen species (ROS). Metabolomic analysis showed a clear signature of increased glucose uptake and utilization in ccRCC tumor samples. Elevated levels of glucose-6-phosphate dehydrogenase (G6PDH) in association with higher levels of PPP-derived metabolites, suggested a prominent role of this pathway in RCC-associated metabolic alterations. G6PDH inhibition, caused a significant decrease in cancer cell survival, a decrease in NADPH levels, and an increased production of ROS, suggesting that the PPP plays an important role in the regulation of ccRCC redox homeostasis. Patients with high levels of glycolytic enzymes had reduced progression-free and cancer-specific survivals as compared to subjects with low levels. Our data suggest that oncogenic signaling pathways may promote ccRCC through rerouting the sugar metabolism. Blocking the flux through this pathway may serve as a novel therapeutic target.

  18. DNA methylation biomarkers predict progression-free and overall survival of metastatic renal cell cancer (mRCC treated with antiangiogenic therapies.

    Directory of Open Access Journals (Sweden)

    Inga Peters

    Full Text Available VEGF-targeted therapy increases both the progression-free (PFS and overall survival (OS of patients with metastasized renal cell cancer (mRCC. Identification of molecular phenotypes of RCC could improve risk-stratification and the prediction of the clinical disease course. We investigated whether gene-specific DNA hypermethylation can predict PFS and OS among patients undergoing anti-VEGF-based therapy. Primary tumor tissues from 18 patients receiving targeted therapy were examined retrospectively using quantitative methylation-specific PCR analysis of CST6, LAD1, hsa-miR-124-3, and hsa-miR-9-1 CpG islands. PFS and OS were analyzed for first-line and sequential antiangiogenic therapies using the log rank statistics. Sensitivity and specificity were determined for predicting first-line therapy failure. Hypermethylation of CST6 and LAD1 was associated with both a shortened PFS (log rank p = 0.009 and p = 0.004 and OS (p = 0.011 and p = 0.043. The median PFS observed for the high and low methylation groups of CST6 and LAD1 was 2.0 vs.11.4 months. LAD1 methylation had a specificity of 1.0 (95% CI 0.65-1.0 and a sensitivity of 0.73 (95% CI 0.43-0.90 for the prediction of first-line therapy. CST6 and LAD1 methylation are candidate epigenetic biomarkers showing unprecedented association with PFS and OS as well as specificity for the prediction of the response to therapy. DNA methylation markers should be considered for the prospective evaluation of larger patient cohorts in future studies.

  19. Joint Effect of Urinary Total Arsenic Level and VEGF-A Genetic Polymorphisms on the Recurrence of Renal Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Shu-Mei Yang

    Full Text Available The results of our previous study suggested that high urinary total arsenic levels were associated with an increased risk of renal cell carcinoma (RCC. Germline genetic polymorphisms might also affect cancer risk and clinical outcomes. Vascular endothelial growth factor (VEGF plays an important role in vasculogenesis and angiogenesis, but the combined effect of these factors on RCC remains unclear. In this study, we explored the association between the VEGF-A -2578C>A, -1498T>C, -1154G>A, -634G>C, and +936C>T gene polymorphisms and RCC. We also evaluated the combined effects of the VEGF-A haplotypes and urinary total arsenic levels on the prognosis of RCC. This case-control study was conducted with 191 RCC patients who were diagnosed with renal tumors on the basis of image-guided biopsy or surgical resections. An additional 376 age- and gender-matched controls were recruited. Concentrations of urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotyping was investigated using fluorescent-based TaqMan allelic discrimination. We observed no significant associations between VEGF-A haplotypes and RCC risk. However, the VEGF-A ACGG haplotype from VEGF-A -2578, -1498, -1154, and -634 was significantly associated with an increased recurrence of RCC (OR = 3.34, 95% CI = 1.03-10.91. Urinary total arsenic level was significantly associated with the risk of RCC in a dose-response manner, but it was not related to the recurrence of RCC. The combination of high urinary total arsenic level and VEGF-A risk haplotypes affected the OR of RCC recurrence in a dose-response manner. This is the first study to show that joint effect of high urinary total arsenic and VEGF-A risk haplotypes may influence the risk of RCC recurrence in humans who live in an area without obvious arsenic exposure.

  20. The Place of FDG PET/CT in Renal Cell Carcinoma: Value and Limitations

    Science.gov (United States)

    Liu, Yiyan

    2016-01-01

    Unlike for most other malignancies, application of FDG PET/CT is limited for renal cell carcinoma (RCC), mainly due to physiological excretion of 18F-fluoro-2-deoxy-2-d-glucose (FDG) from the kidneys, which decreases contrast between renal lesions and normal tissue, and may obscure or mask the lesions of the kidneys. Published clinical observations were discordant regarding the role of FDG PET/CT in diagnosing and staging RCC, and FDG PET/CT is not recommended for this purpose based on current national and international guidelines. However, quantitative FDG PET/CT imaging may facilitate the prediction of the degree of tumor differentiation and allows for prognosis of the disease. FDG PET/CT has potency as an imaging biomarker to provide useful information about patient’s survival. FDG PET/CT can be effectively used for postoperative surveillance and restaging with high sensitivity, specificity, and accuracy, as early diagnosis of recurrent/metastatic disease can drastically affect therapeutic decision and alter outcome of patients. FDG uptake is helpful for differentiating benign or bland emboli from tumor thrombosis in RCC patients. FDG PET/CT also has higher sensitivity and accuracy when compared with bone scan to detect RCC metastasis to the bone. FDG PET/CT can play a strong clinical role in the management of recurrent and metastatic RCC. In monitoring the efficacy of new target therapy such as tyrosine kinase inhibitors (TKIs) treatment for advanced RCC, FDG PET/CT has been increasingly used to assess the therapeutic efficacy, and change in FDG uptake is a strong indicator of biological response to TKI.

  1. The Place of FDG PET/CT in Renal Cell Carcinoma: Value and Limitations.

    Science.gov (United States)

    Liu, Yiyan

    2016-01-01

    Unlike for most other malignancies, application of FDG PET/CT is limited for renal cell carcinoma (RCC), mainly due to physiological excretion of 18F-fluoro-2-deoxy-2-d-glucose (FDG) from the kidneys, which decreases contrast between renal lesions and normal tissue, and may obscure or mask the lesions of the kidneys. Published clinical observations were discordant regarding the role of FDG PET/CT in diagnosing and staging RCC, and FDG PET/CT is not recommended for this purpose based on current national and international guidelines. However, quantitative FDG PET/CT imaging may facilitate the prediction of the degree of tumor differentiation and allows for prognosis of the disease. FDG PET/CT has potency as an imaging biomarker to provide useful information about patient's survival. FDG PET/CT can be effectively used for postoperative surveillance and restaging with high sensitivity, specificity, and accuracy, as early diagnosis of recurrent/metastatic disease can drastically affect therapeutic decision and alter outcome of patients. FDG uptake is helpful for differentiating benign or bland emboli from tumor thrombosis in RCC patients. FDG PET/CT also has higher sensitivity and accuracy when compared with bone scan to detect RCC metastasis to the bone. FDG PET/CT can play a strong clinical role in the management of recurrent and metastatic RCC. In monitoring the efficacy of new target therapy such as tyrosine kinase inhibitors (TKIs) treatment for advanced RCC, FDG PET/CT has been increasingly used to assess the therapeutic efficacy, and change in FDG uptake is a strong indicator of biological response to TKI. PMID:27656421

  2. Combination of mTOR and MAPK Inhibitors—A Potential Way to Treat Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ashutosh Chauhan

    2016-10-01

    Full Text Available Renal cell carcinoma (RCC is the most common neoplasm that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In the past few years, there have been significant advancements to understand the biology of RCC. This has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. Patients treated with targeted therapies for RCC had shown positive impact on overall survival, however, no cure is possible and patients need to undergo treatment for long periods of time, which raises challenges to manage the associated adverse events. Moreover, many patients may not respond to it and even response may not last long enough in the responders. Many inhibitors of the Mammalian target of Rapamycin (mTOR signaling pathway are currently being used in treatment of advanced RCC. Studies showed that inhibitions of mTOR pathways induce Mitogen-Activated Protein Kinase (MAPK escape cell death and cells become resistant to mTOR inhibitors. Because of this, there is a need to inhibit both pathways with their inhibitors comparatively for a better outcome and treatment of patients with RCC.

  3. Merkel cell carcinoma.

    Science.gov (United States)

    Minokadeh, Ardalan; Wulkan, Adam J; Beer, Kenneth; Waibel, Jill S

    2014-01-01

    A 92-year-old man presented for evaluation with a 1-month history of a rapidly growing asymptomatic pink nodule on his forearm. Biopsy results of the lesion demonstrated pathology consistent with Merkel cell carcinoma (MCC). Immunohistochemical studies displayed positive cytoplasmic staining for cytokeratin AE1/AE3, positive dot-like perinuclear staining for cytokeratin-20, diffuse cytoplasmic staining for neuron specific enolase, and no significant staining for S-100. Subsequent positron emission tomography did not reveal evidence of metastatic disease. Wide excision of the lesion was performed along with a sentinel node biopsy of his left axilla. The sentinel nodes were negative for MCC. Adjuvant radiation treatment of the tumor site was provided because the pathologist noted MCC within 2 mm of the deep margin. PMID:24933855

  4. Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3

    NARCIS (Netherlands)

    Purdue, Mark P.; Johansson, Mattias; Zelenika, Diana; Toro, Jorge R.; Scelo, Ghislaine; Moore, Lee E.; Prokhortchouk, Egor; Wu, Xifeng; Kiemeney, Lambertus A.; Gaborieau, Valerie; Jacobs, Kevin B.; Chow, Wong-Ho; Zaridze, David; Matveev, Vsevolod; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S.; Davis, Faith G.; Schwartz, Kendra L.; Banks, Rosamonde E.; Selby, Peter J.; Harnden, Patricia; Berg, Christine D.; Hsing, Ann W.; Grubb, Robert L.; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J.; Quiros, Jose Ramon; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Allen, Naomi E.; Bueno-de-Mesquita, H. Bas; Peeters, Petra H. M.; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Borje; Overvad, Kim; Tjonneland, Anne; Romieu, Isabelle; Riboli, Elio; Mukeria, Anush; Shangina, Oxana; Stevens, Victoria L.; Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan M.; Pharoah, Paul D.; Easton, Douglas F.; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Njolstad, Inger; Tell, Grethe S.; Stoltenberg, Camilla; Kumar, Rajiv; Koppova, Kvetoslava; Cussenot, Olivier; Benhamou, Simone; Oosterwijk, Egbert; Vermeulen, Sita H.; Aben, Katja K. H.; van der Marel, Saskia L.; Ye, Yuanqing; Wood, Christopher G.; Pu, Xia; Mazur, Alexander M.; Boulygina, Eugenia S.; Chekanov, Nikolai N.; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Blanche, Helene; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F.; Skryabin, Konstantin G.; McKay, James D.; Rothman, Nathaniel; Chanock, Stephen J.; Lathrop, Mark; Brennan, Paul

    2011-01-01

    We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and

  5. Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

    NARCIS (Netherlands)

    Patard, J.J.; Kim, H.L.; Lam, J.; Dorey, F.J.; Pantuck, A.J.; Zisman, A.; Ficarra, V.; Han, K.R.; Cindolo, L.; Taille, A. De La; Tostain, J.; Artibani, W.; Dinney, C.P.; Wood, C.G.; Swanson, D.A.; Abbou, C.C.; Lobel, B.; Mulders, P.F.A.; Chopin, D.K.; Figlin, R.A.; Belldegrun, A.S.

    2004-01-01

    PURPOSE: To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS: 4,202 patients from eight internationa

  6. Safety and clinical effect of subcutaneous human interleukin-21 in patients with metastatic melanoma or renal cell carcinoma: a phase I trial

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Brown, Janet; Mouritzen, Ulrik;

    2010-01-01

    This phase I study in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC) evaluated the safety and maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of s.c. treatment of human recombinant interleukin 21 (IL-21)....

  7. Relation of height, body mass, energy intake, and physical activity to 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

    2004-01-01

    Data from the Netherlands Cohort Study on Diet and Cancer were used to investigate the association between anthropometry, energy intake, and physical activity and risk of renal cell carcinoma (RCC). The Netherlands Cohort Study on Diet and Cancer consists of 120,852 men and women aged 55-69 years wh

  8. Renal Cell Carcinoma Initially Presenting as an Arteriovenous Malformation: A Case Presentation and a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Samuel Volin

    2013-01-01

    Full Text Available We describe a case of a patient who presented with hematuria and was diagnosed with a renal arteriovenous malformation (AVM. Transcatheter arterial embolization subsequently was performed on this lesion multiple times. Follow-up imaging demonstrated that the AVM was masking an underlying, rapidly growing renal cell carcinoma (RCC. We describe the pathological and radiographic characteristics of AVMs and RCC. We describe the strengths and weaknesses of computed tomography (CT and magnetic resonance imaging (MRI to detect and characterize RCC and AVM. We recommend initial and follow-up MR imaging in patients with an AVM to establish a baseline, monitor treatment response, and survey lesions for underlying and obscured malignancy.

  9. Role of imaging in successful management of malignant ovarian vein thrombosis in RCC.

    Science.gov (United States)

    Goyal, Ankur; Rangarajan, Krithika; Singh, Prabhjot; Das, Chandan Jyoti

    2014-02-07

    Renal cell carcinoma (RCC) is the most common renal malignancy in adults. Since complete surgical resection is the treatment of choice, accurate staging and extent delineation are imperative for optimal management. Owing to venous tropism, the tumour has a propensity to extend into renal vein and/or inferior vena cava. However, contiguous gonadal vein extension has rarely been reported. Here we present an unusual case of a 65-year-old woman who demonstrated a large left renal mass with extension of tumour thrombus into the left renal and ovarian veins with multiple retroperitoneal venous collaterals detected on multiphasic CT examination. This preoperative imaging information facilitated en bloc resection of the tumour and thrombosed vessels. To the best of our knowledge, this is the first case where comprehensive imaging evaluation enabled successful surgical management of RCC with malignant ovarian vein thrombosis and limited peroperative complications.

  10. Evaluation of EGFR, KRAS and BRAF gene mutations in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Omer Bayrak

    2014-08-01

    Full Text Available A subset of renal cell carcinoma (RCC patients has been shown to respond to anti-EGFR therapy. As KRAS and BRAF mutations are associated with poor response to anti-EGFR therapy in some cancers, it has been suggested that screening for KRAS and BRAF mutations in RCC may be a promising strategy to identify patients who might respond to EGFR-targeted therapy. The aim of this study was to investigate the mutation status of EGFR, KRAS and BRAF in RCC patients. Renal tumors and normal renal samples from forty-eight patients who underwent radical or partial nephrectomy for kidney cancer were used in this study. Histological classification of the tumors was performed according to International Union against Cancer (UICC / American Joint Committee on Cancer (AJCC classification. Seventeen patients (48% had clear-cell RCC, 7 (20% had chromophobe RCC, and 11 patients (32% had papillary RCC. DNA isolated from the samples was subjected to melting curve mutation analysis for EGFR, BRAF and KRAS using ABI-3130 DNA sequencer. DNA sequencing analysis of RCC samples, when compared with morphologically normal matched regions, did not show any exon mutations. Our results do not support the notion that EGFR, KRAS and BRAF might be mutated in RCC. Normal 0 false false false TR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0cm; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-ansi-language:TR; mso-fareast-language:EN-US;}

  11. Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells

    Science.gov (United States)

    Küper, Christoph; Beck, Franz-Xaver; Neuhofer, Wolfgang

    2016-01-01

    The chemokine monocyte chemoattractant protein-1 [MCP-1; also known as chemokine (C-C motif) ligand 2] is an important mediator of monocyte recruitment during inflammatory processes. Pathologically high expression levels of MCP-1 by tumor cells have been observed in a variety of cancer types. In the majority of cases, high MCP-1 expression is associated with a poor prognosis, as infiltration of the tumor with inflammatory monocytes promotes tumor progression and metastasis. MCP-1 is also expressed in renal cell carcinoma (RCC). In the present study, the function and the regulation of MCP-1 was investigated in two RCC cell lines, CaKi-1 and 786-O. In both cell lines, expression of MCP-1 was significantly enhanced compared with non-cancerous control cells. As expected, secretion of MCP-1 into the medium facilitated the recruitment of peripheral blood monocytes via the chemokine (C-C motif) receptor type 2 (CCR2). As expression of CCR2 was also detected in 786-O and CaKi-1 cells, the effect of autocrine MCP-1/CCR2 signaling was evaluated in these cells. In proliferation assays, administration of an MCP-1 neutralizing antibody or of a CCR2 antagonist to CaKi-1 and 786-O cells significantly decreased cell growth; supplementation of the growth medium with recombinant human MCP-1 had no additional effect on proliferation. The migration ability of RCC cells was impaired by MCP-1 neutralization or pharmacological CCR2 inhibition, while it was stimulated by the addition of recombinant human MCP-1, compared with untreated control cells. Finally, substantial differences in the regulation of MCP-1 expression were observed between RCC cell lines. In CaKi-1 cells, expression of MCP-1 appears to be largely mediated by the transcription factor nuclear factor of activated T cells 5, while in 786-O cells, deletion of the tumor suppressor gene Von-Hippel-Lindau appeared to be responsible for MCP-1 upregulation, as suggested by previous studies. Taken together, the results of the

  12. Correlation between Dynamic Spiral-CT Enhancement Parameters and Tumor Angiogenesis in Renal Cell Carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jinhong Wang; Weixia Chen; Xiuhui Zhang; Pengqiu Min; Rongbo Liu; Hengxuan Yang

    2005-01-01

    OBJECTIVE To prospectively investigate the correlation between the enhancement parameters of a dynamic-CT (D-CT) scan for renal cell carcinomas (RCC) and the carcinoma tissue microvessel density (MVD) in renal cell carcinomas (RCC).METHODS Twenty-four cases of renal cell carcinoma verifyied by histopathology were scanned via dynamic-CT, followed by a whole kidney scan. Enhancement parameters were derived as follows .The slope of the contrast media uptake curve (S), area under the curve(AR), the density difference before and after tissue enhancement (△HU) and tissue blood ratio (TBR) were calculated for all lesions. Time-density curve types were ranked from the lowest to the highest of the slope of the contrast media uptake curve (S) as type A, B and C. Pathologic slides corresponding to the CT imagings were subjected to CD34 monoclonal antibodies, then were evaluated with an image analyzer to count hot spots of MVD. By using the Spearman rank correlation tests, statistical analysis was performed to determine the strength of the relationship between enhancement parameters and MVD determinations.RESULTS The carcinoma tissue MVD showed a direct correlation with the enhancement parameters of D-CT (r=0.54, r=0.62, r=0.55, r=0.64, r=0.44,P< 0.05). Moreover the S, △HU, TBR and type curves all demonstrated a strong correlation with the MVD. By analyzing the various enhancement parameters of the time-density curves, the relationship between the enhancement CT parameters corresponding to the tumor's MVD was identified.CONCLUSION A dynamic spiral-CT scan may be a helpful method as a measurement of tumor angiogenesis in vivo in RCC.

  13. Clinical experience and critical evaluation of the role of sorafenib in renal cell carcinoma

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    Zustovich F

    2011-05-01

    Full Text Available Fable Zustovich1, Giuseppe Lombardi1, Davide Pastorelli1, Patrizia Farina1, Massimo Dal Bianco2, Luca De Zorzi2, Maurizia Dalla Palma1, Ornella Nicoletto1, Vittorina Zagonel11Oncologia Medica 1, Istituto Oncologico Veneto-IRCCS, Padova, Italy; 2UO Urologia, Ospedale Sant'Antonio, ULSS 16, Padova, ItalyAbstract: Renal cell carcinoma (RCC is a common malignancy worldwide with approximately 95,000 new cases per year and ranks as the sixth cause of cancer deaths. Until recently, the slightly active and very toxic cytokines were available for patients with advanced RCC. Advances have been made in understanding the molecular biology of renal cancer. The introduction of targeted agents has led to promising possibilities for treating these highly vascularized tumors. Angiogenesis inhibition is likely to represent the main potential therapeutic target. Sorafenib is an oral multikinase inhibitor with activity against tyrosine kinase receptors that are responsible for blood vessel development and has shown to be active in treating advanced RCC. In this review, we summarize the pharmacology, mode of action, pharmacokinetics, and safety of sorafenib use in therapy for advanced RCC.Keywords: sorafenib, pharmacokinetics, angiogenesis 

  14. Increased interferon alpha receptor 2 mRNA levels is associated with renal cell carcinoma metastasis

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    Yamanishi Tomonori

    2007-08-01

    Full Text Available Abstract Background Interferon-α (IFN-α is one of the central agents in immunotherapy for renal cell carcinoma (RCC and binds to the IFN-α receptor (IFNAR. We investigated the role of IFNAR in RCC. Methods We quantified IFNAR mRNA expression in paired tumor and non-tumor samples from the surgical specimens of 103 consecutive patients with RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR, and IFNAR2 protein using Western blotting. Results The absolute level of IFNAR1 and IFNAR2 mRNAs in tumor and non-tumor tissues did not correlate with the malignant and metastatic profiles. The relative yields of the PCR product from the tumor tissue to that from the corresponding non-tumor tissue (T/N for the expression of IFNAR mRNAs were calculated. While the T/N ratio of IFNAR1 did not correlate with any factor, a high T/N ratio of IFNAR2 correlated with poor differentiation (P P P P P Conclusion IFNAR2 is associated with the progression of RCC.

  15. Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma.

    Science.gov (United States)

    Bukowski, Ronald M

    2010-05-01

    Treatment options for patients with metastatic renal cell carcinoma (RCC) have changed dramatically, and a new paradigm has evolved. IFN-alpha and IL-2 were previously mainstays of therapy, but since December 2005, six new agents have been approved in the USA for the treatment of advanced RCC. Three of these new agents are multitargeted kinase inhibitors, including sunitinib, sorafenib, and recently pazopanib, two target the mTOR (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with IFN-alpha) that targets VEGF. Sunitinib has emerged as the standard of care for treatment-naive RCC patients, with the recently approved bevacizumab and IFN-alpha combination providing an additional option for this population. The recent approval of pazopanib, based on the results from sequential Phase II and III clinical trials demonstrating improved overall response rates and progression-free survival, provides yet another option for front-line therapy. The current article examines the pazopanib preclinical and clinical data, provides an overview of the development of this tyrosine kinase inhibitor, and provides some speculation concerning its role in RCC therapy.

  16. Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Gigante, Margherita; Lucarelli, Giuseppe; Divella, Chiara; Netti, Giuseppe Stefano; Pontrelli, Paola; Cafiero, Cesira; Grandaliano, Giuseppe; Castellano, Giuseppe; Rutigliano, Monica; Stallone, Giovanni; Bettocchi, Carlo; Ditonno, Pasquale; Gesualdo, Loreto; Battaglia, Michele; Ranieri, Elena

    2015-11-01

    Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and clear cell RCC (ccRCC), that has a high metastatic index and high relapse rate, is the most common histological subtype. The identification of new biomarkers in ccRCC is fundamental for stratifying patients into prognostic risk groups and to guide therapy. The renoprotective antiaging gene, αKlotho, has recently been found to work as a tumor suppressor in different human cancers. Here, we evaluated αKlotho expression in tissue and serum of ccRCC patients and correlated it with disease progression. Tissue αKlotho expression was studied by quantitative RT-PCR and immunohistochemistry. In addition, soluble serum αKlotho levels were preoperatively measured in 160 patients who underwent nephrectomy for RCC with ELISA. Estimates of cancer-specific (CSS) and progression-free survival (PFS) were calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS and PFS. αKlotho protein levels were significantly decreased in RCC tissues compared with normal tissues (P < 0.01) and the more advanced the disease, the more evident the down-regulation. This trend was also observed in serum samples. Statistically significant differences resulted between serum αKlotho levels and tumor size (P = 0.003), Fuhrman grade (P = 0.007), and clinical stage (P = 0.0004). CSS and PFS were significantly shorter in patients with lower levels of αKlotho (P < 0.0001 and P = 0.0004, respectively). At multivariate analysis low serum levels of αKlotho were independent adverse prognostic factors for CSS (HR = 2.11; P = 0.03) and PFS (HR = 2.18; P = 0.03).These results indicate that a decreased αKlotho expression is correlated with RCC progression, and suggest a key role of declining αKlotho in the onset of cancer metastasis. PMID:26559258

  17. Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma.

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    Benjamin A Neely

    Full Text Available Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC. This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of VHL that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC. Using pooled samples 1551 proteins were identified, of which 290 were differentially abundant, while 783 proteins were identified using individual samples, with 344 being differentially abundant. These 344 differentially abundant proteins were enriched in metabolic pathways and further examination revealed metabolic dysfunction consistent with the Warburg effect. Additionally, the protein data indicated activation of ESRRA and ESRRG, and HIF1A, as well as inhibition of FOXA1, MAPK1 and WISP2. A subset analysis of complementary gene expression array data on 47 pairs of these same tissues indicated similar upstream changes, such as increased HIF1A activation with stage, though ESRRA and ESRRG activation and FOXA1 inhibition were not predicted from the transcriptomic data. The activation of ESRRA and ESRRG implied that HIF2A may also be activated during later stages of ccRCC, which was confirmed in the transcriptional analysis. This combined analysis highlights the importance of HIF1A and HIF2A in developing the ccRCC molecular phenotype as well as the potential involvement of ESRRA and ESRRG in driving these changes. In addition, cofilin-1, profilin-1, nicotinamide N-methyltransferase, and fructose-bisphosphate aldolase A were identified as candidate markers of late stage ccRCC. Utilization of data collected from heterogeneous biological domains strengthened

  18. Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Neely, Benjamin A; Wilkins, Christopher E; Marlow, Laura A; Malyarenko, Dariya; Kim, Yunee; Ignatchenko, Alexandr; Sasinowska, Heather; Sasinowski, Maciek; Nyalwidhe, Julius O; Kislinger, Thomas; Copland, John A; Drake, Richard R

    2016-01-01

    Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC). This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of VHL that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC. Using pooled samples 1551 proteins were identified, of which 290 were differentially abundant, while 783 proteins were identified using individual samples, with 344 being differentially abundant. These 344 differentially abundant proteins were enriched in metabolic pathways and further examination revealed metabolic dysfunction consistent with the Warburg effect. Additionally, the protein data indicated activation of ESRRA and ESRRG, and HIF1A, as well as inhibition of FOXA1, MAPK1 and WISP2. A subset analysis of complementary gene expression array data on 47 pairs of these same tissues indicated similar upstream changes, such as increased HIF1A activation with stage, though ESRRA and ESRRG activation and FOXA1 inhibition were not predicted from the transcriptomic data. The activation of ESRRA and ESRRG implied that HIF2A may also be activated during later stages of ccRCC, which was confirmed in the transcriptional analysis. This combined analysis highlights the importance of HIF1A and HIF2A in developing the ccRCC molecular phenotype as well as the potential involvement of ESRRA and ESRRG in driving these changes. In addition, cofilin-1, profilin-1, nicotinamide N-methyltransferase, and fructose-bisphosphate aldolase A were identified as candidate markers of late stage ccRCC. Utilization of data collected from heterogeneous biological domains strengthened the findings from

  19. A Clear Cell Renal Cell Carcinoma Inhibiting the Response to Intravitreal Antivascular Endothelial Growth Factor Therapy in Wet Age-Related Macular Disease

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    Manuel S. Falcão

    2012-12-01

    Full Text Available Purpose: Wet age-related macular degeneration (AMD is an ocular disorder that can be successfully treated with intravitreal antivascular endothelial growth factor (VEGF therapy. We report a case of incomplete response to intravitreal therapy associated with a clear cell renal cell carcinoma (ccRCC. Methods: A 72-year-old male with wet AMD responded poorly to intravitreal bevacizumab and ranibizumab injections. The removal of a ccRCC led to the spontaneous stabilization of the choroidal neovascular lesion. The renal carcinoma was examined for Von Hippel-Lindau (VHL gene alterations. Immunohistochemical profiling of the hypoxia-inducible factor (HIF pathway addressing the marker HIF-1α and its downstream targets VEGF, glucose transporter 1 and carbonic anhydrase IX was performed. Results: Genotyping of the ccRCC revealed the presence of a truncating VHL mutation (p.E134fs*25. Immunohistochemistry displayed HIF pathway target activation and VEGF expression in the ccRCC tumour cells. Following tumour removal, the neovascular lesion remained stable for 6 months without any further anti-VEGF therapy. Conclusion: The somatic VHL mutation correlates with persistent high levels of HIF-1α pathway targets and VEGF expression in the ccRCC. We postulate that this increased VEGF in the tumour and subsequently in the plasma levels could have caused the incomplete response to intravitreal anti-VEGF therapy. Stabilization of the wet AMD following tumour removal indicates that the angiogenic secreting tumour (ccRCC abrogates the response to VEGF inhibitor therapy. Thus, in cases of poor response to intravitreal anti-VEGF therapy, systemic evaluation including plasma levels of VEGF and/or systemic screening for VEGF-producing tumours should be considered.

  20. Synchronous thyroid carcinoma and squamous cell carcinoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Seo [Chonnam National Univ. School of Dentistry, Kwangju (Korea, Republic of)

    2006-12-15

    Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (SCC) is unusual. This report presents a synchronous thyroid carcinoma and squamous cell carcinoma in the anterior palate region of a 41-year-old man. The clinical, radiologic, and histologic features are described. At 10-month follow-up after operation, no evidence of recurrence ana metastasis was present.

  1. Primary clear cell renal carcinoma cells display minimal mitochondrial respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition by 3-Bromopyruvate.

    Science.gov (United States)

    Nilsson, H; Lindgren, D; Mandahl Forsberg, A; Mulder, H; Axelson, H; Johansson, M E

    2015-01-01

    Changes of cellular metabolism are an integral property of the malignant potential of most cancer cells. Already in the 1930s, Otto Warburg observed that tumor cells preferably utilize glycolysis and lactate fermentation for energy production, rather than the mitochondrial oxidative phosphorylation dominating in normal cells, a phenomenon today known as the Warburg effect. Even though many tumor types display a high degree of aerobic glycolysis, they still retain the activity of other energy-producing metabolic pathways. One exception seems to be the clear cell variant of renal cell carcinoma, ccRCC, where the activity of most other pathways than that of glycolysis has been shown to be reduced. This makes ccRCC a promising candidate for the use of glycolytic inhibitors in treatment of the disease. However, few studies have so far addressed this issue. In this report, we show a strikingly reduced mitochondrial respiratory capacity of primary human ccRCC cells, resulting in enhanced sensitivity to glycolytic inhibition by 3-Bromopyruvate (3BrPA). This effect was largely absent in established ccRCC cell lines, a finding that highlights the importance of using biologically relevant models in the search for new candidate cancer therapies. 3BrPA markedly reduced ATP production in primary ccRCC cells, followed by cell death. Our data suggest that glycolytic inhibitors such as 3BrPA, that has been shown to be well tolerated in vivo, should be further analyzed for the possible development of selective treatment strategies for patients with ccRCC. PMID:25569102

  2. 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.

  3. Glucocorticoids Suppress Renal Cell Carcinoma Progression by Enhancing Na,K-ATPase Beta-1 Subunit Expression

    Science.gov (United States)

    Huynh, Thu P.; Barwe, Sonali P.; Lee, Seung J.; McSpadden, Ryan; Franco, Omar E.; Hayward, Simon W.; Damoiseaux, Robert; Grubbs, Stephen S.; Petrelli, Nicholas J.; Rajasekaran, Ayyappan K.

    2015-01-01

    Glucocorticoids are commonly used as palliative or chemotherapeutic clinical agents for treatment of a variety of cancers. Although steroid treatment is beneficial, the mechanisms by which steroids improve outcome in cancer patients are not well understood. Na,K-ATPase beta-subunit isoform 1 (NaK-β1) is a cell-cell adhesion molecule, and its expression is down-regulated in cancer cells undergoing epithelial-to mesenchymal-transition (EMT), a key event associated with cancer progression to metastatic disease. In this study, we performed high-throughput screening to identify small molecules that could up-regulate NaK-β1 expression in cancer cells. Compounds related to the glucocorticoids were identified as drug candidates enhancing NaK-β1 expression. Of these compounds, triamcinolone, dexamethasone, and fluorometholone were validated to increase NaK-β1 expression at the cell surface, enhance cell-cell adhesion, attenuate motility and invasiveness and induce mesenchymal to epithelial like transition of renal cell carcinoma (RCC) cells in vitro. Treatment of NaK-β1 knockdown cells with these drug candidates confirmed that these compounds mediate their effects through up-regulating NaK-β1. Furthermore, we demonstrated that these compounds attenuate tumor growth in subcutaneous RCC xenografts and reduce local invasiveness in orthotopically-implanted tumors. Our results strongly indicate that the addition of glucocorticoids in the treatment of RCC may improve outcome for RCC patients by augmenting NaK-β1 cell-cell adhesion function. PMID:25836370

  4. Pulmonary Metastasis of Basal Cell Carcinoma

    OpenAIRE

    Seo, Sang-Hee; Shim, Woo-Haing; SHIN, DONG-HOON; Kim, Yun-Seong; Sung, Hyun-Woo

    2011-01-01

    Although basal cell carcinoma is the most common skin cancer, it rarely metastasizes. Metastatic basal cell carcinoma may, therefore, initially elude diagnosis and management. We describe the case of a patient with a metastatic basal cell carcinoma present in the lungs. The differential diagnosis of suspected metastatic lesions should include metastases from a cutaneous basal cell carcinoma, in addition to those from more commonly metastasizing carcinomas, especially in patients with a histor...

  5. Editor’s Pick: Targeted Agents in Patients with Metastatic Renal Cell Carcinoma on Dialysis: Myths and Reality

    Directory of Open Access Journals (Sweden)

    Annalisa Guida

    2016-07-01

    Full Text Available Agents targeting the vascular endothelial growth factor (VEGF/VEGF receptor (VEGFR pathway, as well as mammalian target of rapamycin (mTOR inhibitors have revolutionised the therapeutic landscape of metastatic renal cell carcinoma (mRCC in the past decade, greatly improving the survival rates of these patients. However, translating results of registrative Phase III trials into everyday clinical practice is often troublesome, since real-world patients are completely different from those enrolled in randomised controlled Phase III trials. Prospective data on active oncological treatments in mRCC patients on dialysis are dramatically lacking. This literature review summarises and critically comments on available data relative to mRCC patients on dialysis receiving either VEGF/VEGFR-targeting agents, or mTOR inhibitors. Although prospective studies would definitely be warranted in these specific patient populations, all the available data suggest that mRCC patients on dialysis have the same outcome, both in terms of efficacy and safety, as mRCC patients with normal or marginally impaired kidney function, when treated with VEGF/VEGFR-targeting agents and/or mTOR inhibitors.

  6. Ruptured renal cell carcinoma in pregnancy: a rare case presentation

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    Prameela RC

    2016-05-01

    Full Text Available Malignancy in pregnancy is rare. Carcinomas in pregnancy are mostly kidney cell mass. Renal cell carcinoma (RCC is the commonest malignancy in pregnancy. Because of softness and increased vascularity, rupture of renal cell carcinoma is not uncommon. Here we are presenting a rare case of renal cell carcinoma in pregnancy with spontaneous rupture resulting in massive hemoperitoneum and serious outcome because of late presentation renal cell carcinoma seldom ruptures. A 26 year old woman G2P1L1 with term pregnancy was referred to hospital 80kms away from periphery with non-progression of labour. There was antenatal record suggesting hypertensive disorder of pregnancy in second trimester. On examination, patient was in hypovolemic shock with profuse distension of abdomen. Diagnosis of abruption grade 3 or rupture uterus was made and immediate laparotomy was done. On opening the abdomen, there was hemoperitoneum but uterus was intact. Emergency LSCS done extracted a stillborn baby. There were no retro placental clots also. There was lot of necrotic tissue in the abdomen and there was a tumour arising from lower pole of left kidney which had invaded the renal vessels and had ruptured. Peripartum hysterectomy and left nephrectomy was done. Women did not respond to treatment and died. The objective of presenting this case is the dilemmas faced by the obstetrician in case of shock in 2nd stage of labour. Simple diagnostic tool like renal ultrasound will help to detect at an early stage which could improve the outcome. All cases of hypertensive disorders of pregnancy should be investigated for secondary causes of hypertension. Abdominal USG must be done for all cases of hypertensive disorders of pregnancy in 2nd trimester. Prompt diagnosis and early treatment is the key in management of such condition in pregnancy. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1677-1679

  7. Optimal management of metastatic renal cell carcinoma: current status.

    Science.gov (United States)

    Escudier, Bernard; Albiges, Laurence; Sonpavde, Guru

    2013-04-01

    The armamentarium for the systemic therapy of advanced renal cell carcinoma (RCC) has undergone dramatic changes over the past 6 years. While high-dose interleukin (IL)-2 remains an option for highly selected good and intermediate risk patients with clear-cell histology because of durable complete responses in a small fraction of patients, cytokine-based therapy including interferon (IFN) has been supplanted by vascular-endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors. Treatment decision is initially based on prognostication of the disease. As metastatic RCC (mRCC) is commonly an indolent disease, a period of observation should always been considered. For good and intermediate risk disease, pazopanib, sunitinib or the combination of bevacizumab plus IFN are considered. Notably, recent data suggest non-inferiority for the efficacy of pazopanib compared to sunitinib coupled with a better toxicity profile. A novel VEGF receptor inhibitor, tivozanib, is expected to be approved based on improvement in PFS when compared to sorafenib in the first-line setting. The use of temsirolimus for poor risk disease is supported by a phase III trial dedicated to this group of patients. The role of cytoreductive nephrectomy in the context of VEGF and mTOR inhibitors is being studied in randomized trials. Selected patients with solitary or oligometastatic disease may be eligible for metastatectomy. Following first-line VEGF inhibitors, second-line therapy with everolimus and axitinib have demonstrated benefits in progression-free survival (PFS). One phase III trial comparing sorafenib and temsirolimus in the post-sunitinib setting showed no difference in PFS, the primary endpoint, but did show a superior overall survival for sorafenib. Sorafenib, pazopanib and axitinib have all demonstrated clinical benefit following cytokines. Therapy following first-line mTOR inhibitors remains undefined, although VEGF inhibitors have demonstrated activity in

  8. Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic renal cell carcinoma: preliminary results from the Danish Renal Cancer Group Study-1

    DEFF Research Database (Denmark)

    Mains, Jill Rachel; Donskov, Frede; Pedersen, Erik Morre;

    2014-01-01

    OBJECTIVES: The aim of this study was to explore the impact of dynamic contrast-enhanced (DCE) computer tomography (CT) as a biomarker in metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Twelve patients with favorable or intermediate Memorial Sloan Kettering Cancer Center risk group...... and clear cell mRCC participating in an ongoing prospective randomized phase II trial comprising interleukin-2-based immunotherapy and bevacizumab were included in this preliminary analysis. All patients had a follow-up time of at least 2 years. Interpretation of DCE-CT (max slope method) was...

  9. Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    GATA-5, a zinc-finger transcription factor and member of the GATA family proteins 1–6, is known to be involved in cellular differentiation. We recently found that tumor-specific hypermethylation of the GATA5 CpG island (CGI) occurs in renal cell carcinoma (RCC) and is associated with an adverse clinical outcome. In this study, we investigated whether epigenetic GATA5 alterations may result in changes in GATA5 mRNA expression levels and correlate with the observed prognostic impact of epigenetic changes in GATA5 in RCC. Quantitative real-time reverse-transcribed polymerase chain reaction was applied to measure relative GATA5 mRNA expression levels in 135 kidney tissue samples, including 77 clear cell RCC (ccRCC) tissues and 58 paired adjacent normal renal tissue samples. Relative GATA5 expression levels were determined using the ΔΔCt method and detection of three endogenous control genes then compared to previously measured values of relative methylation. The mean relative GATA5 mRNA expression level exhibited an approximately 31-fold reduction in tumor specimens compared with corresponding normal tissues (p < 0.001, paired t-test). Decreased GATA5 mRNA expression was inversely correlated with increased GATA5 CGI methylation (p < 0.001) and was associated with shortened recurrence-free survival in ccRCC patients (p = 0.023, hazard ratio = 0.25). GATA5 mRNA expression is decreased in ccRCC, likely due to gene silencing by methylation of the GATA5 CGI. Moreover, reduced GATA5 mRNA levels were associated with a poor clinical outcome, indicating a possible role of GATA5 for the development of aggressive ccRCC phenotypes

  10. Everolimus in the treatment of renal cell carcinoma and neuroendocrine tumors.

    Science.gov (United States)

    Chan, Hiu-yan; Grossman, Ashley B; Bukowski, Ronald M

    2010-08-01

    Renal cell carcinoma (RCC) and neuroendocrine tumors (NET) are uncommon malignancies, highly resistant to chemotherapy, that have emerged as attractive platforms for evaluating novel targeted regimens. Everolimus is an oral rapamycin derivative within the mammalian target of rapamycin class of agents. Preclinical series have shown that everolimus exhibits anticancer effects in RCC and NET cell lines. A phase 3 placebo-controlled study in advanced clear-cell RCC, known as RECORD-1 (for "REnal Cell cancer treatment with Oral RAD001 given Daily"), documented that everolimus stabilizes tumor progression, prolongs progression-free survival and has acceptable tolerability in patients previously treated with the multikinase inhibitors sunitinib and/or sorafenib. Everolimus has been granted regulatory approval for use in sunitinib-pretreated and/or sorafenib-pretreated advanced RCC and incorporated into clinical practice guidelines, and the RECORD-1 safety data are being used to develop recommendations for managing clinically important adverse events in everolimus-treated patients. Ongoing clinical trials are evaluating everolimus as earlier RCC therapy (first-line for advanced disease and as neoadjuvant therapy), in non-clear-cell tumors, and in combination with various other approved or investigational targeted therapies for RCC. Regarding advanced NET, recently published phase 2 data support the ability of everolimus to improve disease control in patients with advanced NET as monotherapy or in combination with somatostatin analogue therapy, octreotide long-acting release (LAR). Forthcoming data from phase 3 placebo-controlled trials of everolimus, one focused on monotherapy for pancreatic NET and the other on combination use with octreotide LAR for patients with advanced NET and a history of carcinoid syndrome, will provide insight into its future place in NET therapy. The results of a number of ongoing phase 3 evaluations of everolimus will determine its broader

  11. Lipid-poor renal angiomyolipoma: Differentiation from clear cell renal cell carcinoma using wash-in and washout characteristics on contrast-enhanced computed tomography

    OpenAIRE

    XIE, PINGKUN; Yang, Zhihui; Yuan, Zheng

    2016-01-01

    In the present study, a total of 82 patients (42 men and 40 women; age range, 24–84 years), including 34 patients with lipid-poor renal angiomyolipoma (AML) and 49 with clear cell renal cell carcinoma (RCC), who had undergone multiphase contrast-enhanced computed tomography (CT) (i.e., CT with unenhanced, corticomedullary, nephrographic and 5-min delay phase scanning) were evaluated. The peak enhancement attenuation value, net enhancement attenuation value, enhancement ratio, washout value an...

  12. AB109. Downregulation of tNASP inhibits proliferation through regulating cell cycle-related proteins and inactive ERK/MAPK signal pathway in renal cell carcinoma cells

    Science.gov (United States)

    Fang, Jianzheng; Wang, Hainan; Cheng, Gong; Wang, Shangqian; Deng, Yunfei; Song, Zhen; Xu, Aiming; Liu, Bianjiang; Wang, Zengjun

    2016-01-01

    Objective Nuclear auto-antigenic sperm protein (NASP), initially described as a highly auto-immunogenic testis and sperm-specific protein, is a histone chaperone that is proved to present in all dividing cells. NASP has two splice variants: testicular NASP (tNASP) and somatic form of NASP (sNASP). Only cancer, germ, transformed, and embryonic cells have a high level of expression of the tNASP. Up to now, little has been known about tNASP in renal cell carcinoma (RCC). In the present study, the molecular mechanism of tNASP in RCC was explored. Methods The expression level of tNASP in 16 paired human RCC specimens was determined. Downregulation of tNASP by small interfering RNA (siRNA) was transfected in RCC cell lines. The effect of downregulation of tNASP by siRNA on cell colony formation and proliferation was examined by colony formation assay and CCK-8 assay, cell cycle was analyzed by flow cytometry, and the expression of cyclin D1 and P21 were detected by Western blotting. ERK/MAPK signaling was also analyzed. Results tNASP has a relative high expression level in human RCC tissues. Via upregulation of P21 and downregulation of cyclinD1, silence of tNASP can inhibit cell proliferation, which induces cell cycle arrest. Furthermore, ERK signaling pathway is confirmed to mediate the regulation of cell cycle-related proteins caused by silence of tNASP. Conclusions Our research demonstrates that knockdown of tNASP effectively inhibits the proliferation and causes G1 phase arrest through ERK/MAPK signal pathway.

  13. Renal cell carcinoma: An update for the practicing urologist

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    Sumanta K. Pal

    2015-01-01

    Full Text Available Systemic therapy for metastatic renal cell carcinoma (mRCC has evolved drastically, with agents targeting vascular endothelial growth factor (VEGF and the mammalian target of rapamycin (mTOR now representing a standard of care. The present paper is to review the current status of relevant clinical trials that were either recently completed or ongoing. (1 Though observation remains a standard of care following resection of localized disease, multiple trials are underway to assess VEGF- and mTOR-directed therapies in this setting. (2 While the preponderance of retrospective data favors cytoreductive nephrectomy in the context of targeted agents, prospective data to support this approach is still forthcoming. (3 The first-line management of mRCC may change substantially with multiple studies exploring vaccines, immune checkpoint inhibitors, and novel targeted agents currently underway. In general, prospective studies that will report within the next several years will be critical in defining the role of adjuvant therapy and cytoreductive nephrectomy. Over the same span of time, the current treatment paradigm for first-line therapy may evolve.

  14. Plasma IFN-γ and IL-6 levels correlate with peripheral T-cell numbers but not toxicity in RCC patients treated with CAR T-cells.

    Science.gov (United States)

    Klaver, Yarne; van Steenbergen, Sabine C L; Sleijfer, Stefan; Debets, Reno; Lamers, Cor H J

    2016-08-01

    Autologous T-cells genetically modified to express a chimeric antigen receptor (CAR) against carboxy-anhydrase-IX (CAIX) were administered to twelve patients with CAIX-positive metastatic renal cell carcinoma. Here, we questioned whether plasma cytokine levels following treatment or in vitro cytokine production from the T-cell infusion products could serve as predictors for peripheral T-cell persistence or in vivo T-cell activity. We demonstrated that CAR surface as well as gene expression are down-regulated following T-cell infusion, and that peripheral numbers of CAR T-cells are best captured by flow cytometry and not by qPCR. Numbers of CAR T-cells in blood correlated with plasma levels of IFN-γ and IL-6, but not with any of the other cytokines tested. Plasma IFN-γ or IL-6 levels did not correlate with liver enzyme values. Thus, out of 27 cytokines tested, IFN-γ and IL-6 levels in plasma are potential surrogate markers for CAR T-cell persistence in solid tumors. PMID:27377533

  15. Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma.

    Science.gov (United States)

    Incorvaia, Lorena; Bronte, Giuseppe; Bazan, Viviana; Badalamenti, Giuseppe; Rizzo, Sergio; Pantuso, Gianni; Natoli, Clara; Russo, Antonio

    2016-04-19

    The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition.Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.

  16. Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Mondal

    2014-01-01

    Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy and cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Here, we report a case of ACC initially diagnosed by computed tomography (CT-guided fine needle aspiration cytology (FNAC with the help of immunocytochemistry. A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. A CT scan of her abdomen revealed a large mass arising from the upper part of the left kidney. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli. Based on cytomorphology, differential diagnoses of ACC and renal cell carcinoma (RCC were made. On immunocytochemistry, the tumor cells were synaptophysin, inhibin, vimentin and Melan-A positive but cytokeratin and epithelial membrane antigen negative. Thus, a cytodiagnosis of myxoid ACC was made and histopathologic examination was suggested. Subsequent histologic examination and immunohistochemistry proved the case to be myxoid ACC.

  17. Chromophobe renal cell cancer - review of the literature and potential methods of treating metastatic disease

    Directory of Open Access Journals (Sweden)

    Bodnar Lubomir

    2009-10-01

    Full Text Available Abstract Chromophobe renal cell carcinoma (ChRCC is a subtype of renal cell carcinoma (RCC. ChRCC is diagnosed mainly in 6th decade of life. An incidence of ChRCC is similar in both men and woman. Eighty six percent of ChRCCs cases are diagnosed in stage 1 or 2. Prognosis of ChRCC is better than in other types of RCC. Five- and 10-year disease free survival (DFS for ChRCC was 83.9% and 77.9%, respectively. Expression of immunohistological markers: cytokeratins (CK, vimentin, epithelial membrane antigen (EMA, CD10 could be potentially helpful in diagnosis of different subtypes of RCC. From all conventional RCC, CD 117 was detected (overexpression in membrane of cells ChRCC. Overexpression of CD117 on cellular membranes of ChRCC could be a potential target for kinase inhibitors like: imatinib, dasatinib, nilotinib. The potential targets for other kinase inhibitors (sunitinib and sorafenib in ChRCC seem to be VEGFR and PDGFR. On the basis for formulating research hypotheses which should be verified by prospective studies.

  18. Survival advantage of partial over radical nephrectomy in patients presenting with localized renal cell carcinoma

    International Nuclear Information System (INIS)

    Partial nephrectomy (PN) preserves renal function and has become the standard approach for T1a renal cell carcinoma (RCC). However, there is still an ongoing debate as to which patients will actually derive greater benefit from partial than from radical nephrectomy (RN). The aim of this study was to retrospectively evaluate the impact of the type of surgery on overall survival (OS) in patients with localized RCC. Renal surgery was performed in 4326 patients with localized RCC (pT ≤ 3a N/M0) at six German tertiary care centers from 1980 to 2010: RN in 2955 cases (68.3%), elective (ePN) in 1108 (25.6%), and imperative partial nephrectomy (iPN) in 263 (6.1%) cases. The median follow-up for all patients was 63 months. Kaplan-Meier and Cox regression analyses were carried out to identify prognosticators for OS. PN was performed significantly more often than RN in patients presenting with lower tumor stages, higher RCC differentiation, and non-clear cell histology. Accordingly, the calculated 5 (10)-year OS rates were 90.0 (74.6)% for ePN, 83.9 (57.5)% for iPN, and 81.2 (64.7)% for RN (p < 0.001). However, multivariate analysis including age, sex, tumor diameter and differentiation, histological subtype, and the year of surgery showed that ePN compared to RN still qualified as an independent factor for improved OS (HR 0.79, 95% CI 0.66-0.94, p = 0.008). Even allowing for the weaknesses of this retrospective analysis, our multicenter study indicates that in patients with localized RCC, PN appears to be associated with better OS than RN irrespective of age or tumor size

  19. Renal cell carcinoma metastases to the pancreas - Value of arterial phase imaging at MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Corwin, Michael T. [Univ. of California, Davis Medical Center, Dept. of Radiology, Sacramento (United States)], e-mail: Michael.corwin@ucdmc.ucdavis.edu; Lamba, Ramit; McGahan, John P. [Univ. of California, Davis Medical Center, Dept. of Radiology, Sacramento (United States); Wilson, Machelle [Univ. of California, Davis, Dept. of Public Health Sciences (United States)

    2013-04-15

    Background: The pancreas is an increasingly recognized site of renal cell carcinoma metastases. It is important to determine the optimal MDCT protocol to best detect RCC metastases to the pancreas. Purpose: To compare the rate of detection of renal cell carcinoma metastases to the pancreas between arterial and portal venous phase MDCT. Material and Methods: A retrospective review of CTs of the abdomen yielded six patients with metastatic RCC to the pancreas. Five of six patients had pathologically proven clear cell RCC. Two blinded reviewers independently reported the number of pancreatic lesions seen in arterial and venous phases. Each lesion was graded as definite or possible. The number of lesions was determined by consensus review of both phases. Attenuation values were obtained for metastatic lesions and adjacent normal pancreas in both phases. Results: There were a total of 24 metastatic lesions to the pancreas. Reviewer 1 identified 20/24 (83.3%) lesions on the arterial phase images and 13/24 (54.2%) lesions on the venous phase. Seventeen of 20 (85.0%) arterial lesions were deemed definite and 9/13 (69.2%) venous lesions were definite. Reviewer 2 identified 19/24 (79.2%) lesions on the arterial phase and 14/24 (58.3%) on the venous phase. Seventeen of 19 (89.5%) arterial lesions were definite and 7/14 (50%) venous lesions were definite. Mean attenuation differential between lesion and pancreas was 114 HU and 39 HU for arterial and venous phases, respectively (P<0.0001). Conclusion: Detection of RCC metastases to the pancreas at MDCT is improved using arterial phase imaging compared to portal venous phase imaging.

  20. Renal cell carcinoma metastases to the pancreas - Value of arterial phase imaging at MDCT

    International Nuclear Information System (INIS)

    Background: The pancreas is an increasingly recognized site of renal cell carcinoma metastases. It is important to determine the optimal MDCT protocol to best detect RCC metastases to the pancreas. Purpose: To compare the rate of detection of renal cell carcinoma metastases to the pancreas between arterial and portal venous phase MDCT. Material and Methods: A retrospective review of CTs of the abdomen yielded six patients with metastatic RCC to the pancreas. Five of six patients had pathologically proven clear cell RCC. Two blinded reviewers independently reported the number of pancreatic lesions seen in arterial and venous phases. Each lesion was graded as definite or possible. The number of lesions was determined by consensus review of both phases. Attenuation values were obtained for metastatic lesions and adjacent normal pancreas in both phases. Results: There were a total of 24 metastatic lesions to the pancreas. Reviewer 1 identified 20/24 (83.3%) lesions on the arterial phase images and 13/24 (54.2%) lesions on the venous phase. Seventeen of 20 (85.0%) arterial lesions were deemed definite and 9/13 (69.2%) venous lesions were definite. Reviewer 2 identified 19/24 (79.2%) lesions on the arterial phase and 14/24 (58.3%) on the venous phase. Seventeen of 19 (89.5%) arterial lesions were definite and 7/14 (50%) venous lesions were definite. Mean attenuation differential between lesion and pancreas was 114 HU and 39 HU for arterial and venous phases, respectively (P<0.0001). Conclusion: Detection of RCC metastases to the pancreas at MDCT is improved using arterial phase imaging compared to portal venous phase imaging

  1. Proposal of “cyclic therapy”, a novel treatment strategy with targeted agents for advanced renal cell carcinoma

    OpenAIRE

    Nozawa, Masahiro; Uemura, Hirotsugu

    2013-01-01

    The number of molecular targeted agents for advanced renal cell carcinoma (RCC) has gradually increased, but evidence on the optimal order of selection for such agents has not yet caught up with this trend. In addition, timing of switching molecular targeted drugs may also become an important issue for controlling the disease as types of these drugs grow in number. Based on the fact that the efficacy of a rechallenge of the drug previously used suggests the recovery of the sensitivity, a cycl...

  2. RESECTION OF THE S-SHAPED CROSSED DYSTOPIC KIDNEY IN A PATIENT WITH RENAL CELL CARCINOMA

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    B. Ya. Alekseev

    2014-07-01

    Full Text Available Renal cell carcinoma (RCC is one of the most urgent topics in modern oncourology. This is attributable to the high morbidity and mortality rates associated with this pathology. Renal dystopia is a rather rare developmental anomaly. The literature data describing cases of the diagnosis and treatment in patients with dystopic kidney malignancies are scarce. Moreover, if a tumor is present in the solitary dystopic kidney, it is often extremely difficult to perform an organ-saving operation for a number of features of the anatomic structure of the dystopic kidney and its vascular architectonics. The paper describes a clinical case of S-shaped crossed dystopic kidney resection in a patient with RCC.

  3. Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients

    DEFF Research Database (Denmark)

    Donskov, Frede; Michaelson, M Dror; Puzanov, Igor;

    2015-01-01

    BACKGROUND: Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities. METHODS: In sunitinib-treated mRCC patients (N=770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure ⩾140 mm Hg......), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand-foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. RESULTS: On-treatment neutropenia and hypertension were associated with longer....... Considering hypertension and neutropenia (developing both vs neither) changed IMDC-predicted median OS in each IMDC risk group (favourable: 45.3 vs 19.5 months; intermediate: 32.5 vs 8.0 months; poor: 21.1 vs 4.8 months). CONCLUSIONS: On-treatment neutropenia and hypertension are independent biomarkers...

  4. The Wide Experience of the Sequential Therapy for Patients with Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Lambea, Julio; Anido, Urbano; Etxániz, Olatz; Flores, Luis; Montesa, Álvaro; Sepúlveda, Juan Manuel; Esteban, Emilio

    2016-11-01

    Sequential targeted therapies are the standard of care for patients with metastatic renal cell carcinoma (mRCC). Several drugs are available for patients whose disease progresses while they receive initial tyrosine kinase inhibitor (TKI) therapy; these include nivolumab (an inhibitor of PD-1 receptor), everolimus (an inhibitor of the mechanistic target of rapamycin) or additional TKIs. Until now, there has been no clinical evidence to support the use of one strategy versus another, so investigators and physicians rely on experience, judgement and findings from molecular analyses to select the appropriate treatment. However, with the arrival of nivolumab and cabozantinib that provide an overall survival higher than other alternative treatments, therapeutic strategies may have changed. Here, we discuss findings from preclinical and clinical studies that might help clinicians to choose the optimal treatment approach for patients with mRCC who progress to initial therapy. PMID:27613167

  5. 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...... (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration......, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS: Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients...

  6. Simultaneous Laryngeal Squamous Cell Carcinoma and Papillary Thyroid Carcinoma

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    Bighan Khademi

    2011-04-01

    Full Text Available The association of squamous cell carcinoma of the larynx with thyroid papillary carcinoma is an unusual finding. From 2004 to 2011, approximately 250 patients underwent laryngectomies due to squamous cell carcinoma of the larynx at the Otolaryngology Department of Khalili Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. In three patients, synchronous occurrence of squamous cell carcinoma and thyroid papillary carcinoma was found. Histopathologic study of the lymph nodes revealed metastatic papillary thyroid carcinoma in one case. We report three cases of thyroid papillary carcinoma incidentally found on histological examinations of resected thyroid lobes, as a procedure required for treatment of head and neck squamous cell carcinoma. In comparison, laryngeal squamous cell carcinoma needs more aggressive treatment than well-differentiated thyroid carcinoma. The prevalence of thyroid papillary carcinoma, as an incidental finding in our study was 0.01%. Therefore, preoperative evaluation of the thyroid gland by ultrasonography and fine needle aspiration biopsy of suspicious lesions is recommended in patients who are candidates for open laryngectomy.

  7. Signalling pathways involved in antitumoral effects of VIP in human renal cell carcinoma A498 cells: VIP induction of p53 expression.

    Science.gov (United States)

    Vacas, Eva; Muñoz-Moreno, Laura; Fernández-Martínez, Ana B; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2014-08-01

    Vasoactive intestinal peptide (VIP) decreases cell proliferation through PI3K signalling and prevents tumour progression in clear renal cell carcinoma (RCC). Here we analyzed the signalling pathways that mediate such VIP effects by using human RCC A498 cells. The effects of treatment with 1 μM VIP and/or specific protein kinase inhibitors such as H89, Wortmannin and PD98059 were studied by cell adhesion assay, ELISA of VEGF165 and ROS production assays. Semiquantitative RT-PCR and western blot were performed to study p53 expression. VIP increased cell adhesion and ROS production, and decreased VEGF165 secretion through PI3K signalling. Moreover, VIP increased nuclear expression of tumour suppressor p53. VIP effects could be blocked by cell incubation with a specific p53 inhibitor, cyclin pifithrin-α hydrobromide (CPFT-αH). In conclusion, this study provides a p53-dependent mechanism by which VIP regulates cell proliferation in RCC development. It supports a potential usefulness of VIP in new therapies of RCC.

  8. Telomerase-pulsed dendritic cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Schmiedel, Alexandra

    2006-02-01

    Full Text Available Objective: Therapeutic vaccination with dendritic cells (DC showed promising results in first clinical trials in cases of metastatic renal cell carcinoma (RCC. Human telomerase reverse transcriptase (hTERT could be a potential target because it is detectable in more than 85% of human tumors including RCC. Design: 10 patients with progressive metastatic RCC were enrolled in a clinical phase I/II trial using DC pulsed with hTERT-peptide. Beside toxicity and feasibility aspects, a complex immune monitoring including in vitro data were evaluated. In addition to detection of tumor-specific effector cells we investigated their functionality like IFN-γ secretion and cytotoxic activity against tumor cells. Results: The vaccine was well tolerated. Two patients showed a mixed response (MR and one patient a stable disease (SD. Interestingly, responders showed cytotoxic activity already before start of therapy and there was a significant increase in cytotoxic activity of effector cells from all responders (SD and MR patients after the first vaccination. In contrast non-responders showed no cytotoxic activity before and during treatment. Therefore, cytotoxic activity might be used as a predictive marker in the future. Tetramer staining detected higher amounts of tumor-specific cytotoxic cells in responding patients compared to non-responders. Also, responders possessed increasing amounts of IFN-γ producing immunological effector cells. Conclusion: Telomerase-pulsed DC could enhance a tumor-specific immune response against RCC.

  9. Famitinib in metastatic renal cell carcinoma: a single center study

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen; ZHOU Ai-ping; QIN Qiong; CHANG Chun-xiao; JIANG Hao-yuan; MA Jian-hui; WANG Jin-wan

    2013-01-01

    Background Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor.The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum.The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).Methods The data of famitinib in treating patients with mRCC from the single-center phases Ⅰ and Ⅱ clinical trials were analyzed.Famitinib was administered orally at the dose of 13-30 mg once daily until tumor progression,occurrence of intolerable adverse reactions or withdrawal of the informed consent.Results A total of 24 patients with mRCC were treated including 17 patients at a dose of 25 mg once daily,4 patients at a dose of 27 mg and 1 patient each at a dose of 13 mg,20 mg and 30 mg,respectively.Twelve (50.0%) patients achieved partial response (PR) and 9 patients achieved stable disease (SD).Progressive disease was found in 3 (12.5%) patients.The disease control rate was 87.5%.The median follow-up time was 17.6 months; the median progression free survival (PFS) was 10.7 (95% Cl7.0-14.4) months; and the estimated median overall survival (OS) time was 33.0 (95% Cl8.7-57.3) months.The adverse drug reactions mainly included hypertension (54.1%),hand-foot skin reactions (45.8%),diarrhea (33.3%),mucositis (29.2%),neutropenia (45.8%),thrombocytopenia (29.2%),hyperlipidemia (41.7%) and proteinuria (41.7%).The incidence rate of grades 3 and 4 adverse events was low,mainly including hypertension 12.5%,hand-foot skin reactions 4.2%,neutropenia 4.2%,thrombocytopenia 4.2%,hyperlipidemia 4.2% and proteinuria 12.5%.Conclusions Famitinib has significant anti-tumor activity in mRCC.The common adverse reactions are generally manageable.

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

    Science.gov (United States)

    van Dijk, Boukje A C; Schouten, Leo J; Kiemeney, Lambertus A L M; Goldbohm, R Alexandra; van den Brandt, Piet A

    2005-11-20

    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 includes 150-item food-frequency questions and additional questions on lifestyle factors, at baseline in 1986. A case-cohort approach was used. After 9.3 years of follow-up, 275 microscopically confirmed incident cases were identified. Subjects with incomplete or inconsistent dietary data were excluded, leaving 260 RCC cases for analyses on fruit consumption and 249 RCC cases for analyses on vegetable consumption. Incidence rate ratios (RR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazard models. RRs for exposure variables are expressed per increment of 25 g/day and are adjusted for age, sex, smoking, body mass index and history of hypertension at baseline. The RRs for vegetable consumption were further adjusted for fruit consumption and vice versa. Total vegetable and fruit consumption (RR: 1.00; 95% CI 0.97-1.02), vegetable (RR: 1.00, 95% CI 0.96-1.06) and fruit consumption (RR: 1.00; 95% CI 0.97-1.03) were not associated with RCC risk. Also, no association existed for botanical subgroups of vegetables and fruit. For 30 individual vegetables and fruits, we observed one that significantly increased RR (mandarin consumption, RR: 1.76; 95% CI 1.28-2.42), which must be regarded cautiously because of multiple testing. These results suggest the absence of an association between vegetable and/or fruit consumption and RCC risk.

  11. Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma

    OpenAIRE

    Wang Yong; Zhang Rui; Wu Donglu; Lu Zhihua; Sun Wentao; Cai Yong; Wang Chunxi; Jin Jingji

    2013-01-01

    Abstract Background MYST1 (also known as hMOF), a member of the MYST family of histone acetyltransferases (HATs) as an epigenetic mark of active genes, is mainly responsible for histone H4K16 acetylation in the cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here we examined the involvement of hMOF expression and histone H4K16 acetylation in primary renal cell carcinoma (RCC). Simultaneously, we investigated the correlation be...

  12. In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Donskov, F; Marcussen, N; Hokland, M;

    2004-01-01

    The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-alpha) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)- and IFN.......016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-alpha in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival....

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

    Directory of Open Access Journals (Sweden)

    Turker Acar

    2014-01-01

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

  14. Biology of Metastatic Renal Cell Carcinoma

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    Michele Milella, Alessandra Felici

    2011-01-01

    Full Text Available In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1 even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2 prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3 although we have successfully identified classes of drugs (or molecular mechanisms of action that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4 finally (and perhaps most importantly, even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer

  15. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

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    Divvya

    2014-05-01

    Full Text Available Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differentiation is practically very rare.

  16. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    OpenAIRE

    Divvya; Rehana; Viswanathan; Krishnaswamy; Anvar Ali

    2014-01-01

    Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differen...

  17. Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma

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    Fairfax BP

    2012-12-01

    Full Text Available Abstract Background Sorafenib is an orally available kinase inhibitor with activity at Raf, PDGFβ and VEGF receptors that is licensed for the treatment of advanced renal cell carcinoma (RCC and hepatocellular carcinoma (HCC. Current evidence-based post-nephrectomy management of individuals with localized RCC consists of surveillance-based follow up. The SORCE trial is designed to investigate whether treatment with adjuvant sorafenib can reduce recurrence rates in this cohort. Case presentation Here we report an idiosyncratic reaction to sorafenib resulting in fatal hepatotoxicity and associated renal failure in a 62 year-old man treated with sorafenib within the SORCE trial. Conclusion This is the first reported case of sorafenib exposure associated fatal toxicity in the adjuvant setting and highlights the unpredictable adverse effects of novel adjuvant therapies.

  18. Multiparametric magnetic resonance imaging for the differentiation of low and high grade clear cell renal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cornelis, F.; Tricaud, E.; Lasserre, A.S.; Petitpierre, F.; Le Bras, Y.; Bouzgarrou, M.; Grenier, N. [Pellegrin Hospital, Department of Radiology, Bordeaux (France); Bernhard, J.C. [Pellegrin Hospital, Department of Urology, Bordeaux (France); Yacoub, M. [Pellegrin Hospital, Department of Pathology, Bordeaux (France); Ravaud, A. [Saint-Andre Hospital, Department of Oncology, Bordeaux (France)

    2015-01-15

    To retrospectively evaluate the ability of magnetic resonance (MR) imaging to differentiate low from high Fuhrman grade renal cell carcinoma (RCC). MR images from 80 consecutive pathologically proven RCC (57 clear cell, 16 papillary and 7 chromophobe) were evaluated. Double-echo chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps were reviewed independently. Signal intensity index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash-out indices (WoI) between different phases were calculated and compared to pathological grade and size. The Fuhrman scoring system was used. Low grade (score ≤2) and high grade (score ≥3) tumours were compared using univariate and multivariate analyses. No associations between grade and imaging factors were found for papillary and chromophobe RCCs. For clear cell RCCs, there was a significant association between the grade and parenchymal WiI (WiI2) (P = 0.02) or ADCr (P = 0.03). A significant association between tumour grade and size (P = 0.01), WiI2 (P = 0.02) and ADCr (P = 0.05) remained in multivariate analysis. Multiparametric MRI can be used to accurately differentiate low Fuhrman grade clear cell RCC from high grade. High Fuhrman grade (≥3) RCCs were larger, had lower parenchymal wash-in indices and lower ADC ratios than low grade. (orig.)

  19. The joint effects of arsenic and risk diplotypes of insulin-like growth factor binding protein-3 in renal cell carcinoma.

    Science.gov (United States)

    Huang, Chao-Yuan; Huang, Ya-Li; Pu, Yeong-Shiau; Shiue, Horng-Sheng; Chen, Wei-Jen; Chen, Shih-Shan; Lin, Ying-Chin; Su, Chien-Tien; Hsueh, Yu-Mei

    2016-07-01

    The association between renal cell carcinoma (RCC) and diabetes mellitus (DM), alcohol consumption, insulin-like growth factor binding protein-3 (IGFBP-3) gene, and arsenic exposure, has been the subject of independent studies. However, few studies have examined the combined effect of these factors on RCC risk. The aim of this study was to examine the association between these risk factors and the odds ratio (OR) of RCC. A hospital-based case-control study was conducted in 398 RCC patients and 756 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of IRS-1 (Gly972Arg), PI3-K (Met362Ile), IGFBP-3 (A[-202]C), and IGFBP-3 (C[-1590]A) by PCR-RFLP. Profiles of urinary arsenic were measured by high performance liquid chromatography linked with hydride generator and atomic absorption spectrometry. Participants who had never consumed alcohol and who had high total levels of urinary arsenic and DM had a high OR of RCC. IGFBP-3 (A[-202]C) and IGFBP-3 (C[-1590]A) were in linkage disequilibrium. Participants carrying high-risk IGFBP-3 diplotypes A-C/C-C, A-A/A-C, and C-A/C-A had a significantly higher odds ratio (OR) and 95% confidence interval (2.80, 1.91-4.12) of RCC compared to those carrying other IGFBP-3 diplotypes. This is the first study to show that borderline significant interaction of high total levels of urinary arsenic and IGFBP-3 high-risk diplotypes significantly enhanced the OR of RCC. Our data also provide evidence that subjects with more risk factors (e.g., high total levels of urinary arsenic, never consumed alcohol, IGFBP-3 high-risk diplotypes) may experience a higher OR of RCC. PMID:27038904

  20. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  1. Basal cell carcinoma of penis: case report.

    OpenAIRE

    Sulaiman, M Z; Polacarz, S V; Partington, P E

    1988-01-01

    Basal cell carcinoma of the penis is rare. A patient who presented with a penile and scrotal ulcer due to basal cell carcinoma is reported. Wide local excision and split skin grafting were performed to excise the lesion completely.

  2. Identification of Molecular Tumor Markers in Renal Cell Carcinomas with TFE3 Protein Expression by RNA Sequencing

    Directory of Open Access Journals (Sweden)

    Dorothee Pflueger

    2013-11-01

    Full Text Available TFE3 translocation renal cell carcinoma (tRCC is defined by chromosomal translocations involving the TFE3 transcription factor at chromosome Xp11.2. Genetically proven TFE3 tRCCs have a broad histologic spectrum with overlapping features to other renal tumor subtypes. In this study,we aimed for characterizing RCC with TFE3 protein expression. Using next-generation whole transcriptome sequencing (RNA-Seq as a discovery tool, we analyzed fusion transcripts, gene expression profile, and somatic mutations in frozen tissue of one TFE3 tRCC. By applying a computational analysis developed to call chimeric RNA molecules from paired-end RNA-Seq data, we confirmed the known TFE3 translocation. Its fusion partner SFPQ has already been described as fusion partner in tRCCs. In addition, an RNAread-through chimera between TMED6 and COG8 as well as MET and KDR (VEGFR2 point mutations were identified. An EGFR mutation, but no chromosomal rearrangements, was identified in a control group of five clear cell RCCs (ccRCCs. The TFE3 tRCC could be clearly distinguished from the ccRCCs by RNA-Seq gene expression measurements using a previously reported tRCC gene signature. In validation experiments using reverse transcription-PCR, TMED6-COG8 chimera expression was significantly higher in nine TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in 24 ccRCCs (P<.001 and 22 papillaryRCCs (P<.05-.07. Immunohistochemical analysis of selected genes from the tRCC gene signature showed significantly higher eukaryotic translation elongation factor 1 alpha 2 (EEF1A2 and Contactin 3 (CNTN3 expression in 16 TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in over 200 ccRCCs (P < .0001, both.

  3. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  4. Renal clear cell carcinoma metastasis to salivary glands - a series of 9 cases: clinico-pathological study.

    Science.gov (United States)

    Majewska, H; Skálová, A; Radecka, K; Stodulski, D; Hyrcza, M; Stankiewicz, C; Biernat, W

    2016-03-01

    Metastatic tumors involving salivary glands arising from the non-head and neck area are very rare. Renal cell carcinoma (RCC) is known for its high propensity for metastasis to unusual localizations. RCC metastasis to the maxillofacial area is an uncommon event (16%), but metastasis to salivary glands is extremely rare. We report a series of 9 such cases retrieved from two institutions. The group included 6 females and 3 males. The age at diagnosis ranged from 60 to 97 years (mean 72.6 years). The tumors involved the parotid gland in 7 cases, and the submandibular and small salivary gland of the oral cavity in 1 case each. The size of tumors ranged from 0.4 to 5 cm. Total parotidectomy with selective neck dissection was performed in 4 cases, while superficial parotidectomy was performed in 1 case and simple resection in 3 cases. Histologically, all the tumors were clear cell renal cell carcinomas, and therefore the differential diagnosis mainly included clear cell variants of salivary gland carcinomas. The parotid gland was the initial manifestation of renal malignancy in 4 of the cases, while in the remaining 5 cases a history of RCC had been known. The salivary gland involvement developed from 11 months to 13 years after the time of diagnosis of the primary tumor. In 2 cases it was the first site of dissemination. Pathologists need to maintain a high index of suspicion for the possibility of metastasis when confronted with oncocytic or clear cell neoplasms developing in salivary glands. RCC, although rare, should be included in this differential diagnosis. PMID:27179273

  5. Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

    International Nuclear Information System (INIS)

    Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

  6. Docetaxel enhances apoptosis and G2/M cell cycle arrest by suppressing mitogen-activated protein kinase signaling in human renal clear cell carcinoma.

    Science.gov (United States)

    Han, T D; Shang, D H; Tian, Y

    2016-01-01

    Tremendous efforts have been made in renal cell carcinoma (RCC) patients' research; however, clinical findings in patients have been disappointing. The aims of our study were to identify better or alternative therapeutic methods that can reverse chemotherapy resistance and to enhance sensitivity to docetaxel (DOX)-based chemotherapy drugs. We evaluated the anti-proliferative effect of DOX against RCC cells. DOX was found to suppress proliferation of RCC cells under in vitro and in vivo settings. Flow cytometric analysis revealed that DOX suppressed cell growth by induction of both apoptosis and G2/M cell cycle arrest in a dose-dependent manner. Various patterns of gene expression were observed by cluster analysis. In addition, based on network analysis using the ingenuity pathway analysis software, DOX was found to suppress phosphorylation of extracellular signal-regulated kinase 1/2 and p38, suggesting that the mitogen-activated protein kinase signaling pathway plays a vital role in the anti-proliferative effect of DOX against RCC. PMID:26909952

  7. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

    Directory of Open Access Journals (Sweden)

    Ronald M Bukowski

    2010-03-01

    Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, CCF Lerner College of Medicine of CWRU Cleveland, OH, USAAbstract: The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC. One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.Keywords: metastatic renal cell carcinoma, bevacizumab, interferon-α

  8. Antitumor and antiangiogenic activity of Schisandra chinensis polysaccharide in a renal cell carcinoma model.

    Science.gov (United States)

    Qu, Hai-Ming; Liu, Shi-Jian; Zhang, Chun-Ying

    2014-05-01

    The aim of this study was to determine the antitumor and antiangiogenic effects of the Schisandra chinensis polysaccharides (SCP) in selected renal cell carcinoma (RCC) cells and evaluate its potential mechanism of action. In vitro, endothelial growth factor (VEGF) secretion by Caki-1 was blockaded in response to SCP treatment for 48h. In vivo, a significant tumor growth inhibition effect was observed after SCP administration for 4 weeks. Moreover, SCP treatment decreased the level of VEGF, CD31 and CD34 in RCC tumor tissues. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly; the expression of Bax and p53 increased; and the expression of Bcl-2 decreased dramatically in transplanted tumor tissues following SCP administration. These results indicated that the potential mechanisms involved by which SCP exerted its antitumor and antiangiogenic activity might be associated with the up-regulation of Bax and p53, downregulation of Bcl-2, as well as the reduction of VEGF, CD31 and CD34 in xenografted tumors. These findings demonstrated that the SCP is a potential antitumor agent for RCC treatment.

  9. [The Dutch guideline 'Renal cell carcinoma'].

    NARCIS (Netherlands)

    Osanto, S.; Bex, A.; Hulsbergen- van de Kaa, C.A.; Soetekouw, P.M.M.B.; Stemkens, D.

    2012-01-01

    The Dutch guideline 'Renal Cell Carcinoma' has been revised on the basis of new literature. With the assistance of the Netherlands Cancer Registry an assessment was made of the current care for patients with renal cell carcinoma. Renal cell carcinoma is a type of cancer for which knowledge of the ge

  10. Basal cell carcinoma-treatment with cryosurgery

    Directory of Open Access Journals (Sweden)

    Kaur S

    2003-03-01

    Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  11. Basal cell carcinoma-treatment with cryosurgery

    OpenAIRE

    Kaur S; Thami G; Kanwar A

    2003-01-01

    Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  12. Vasoactive intestinal peptide induces oxidative stress and suppresses metastatic potential in human clear cell renal cell carcinoma.

    Science.gov (United States)

    Vacas, Eva; Bajo, Ana M; Schally, Andrew V; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2013-01-30

    Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas (ccRCCs) are poorly understood. A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau (VHL) gene, which contributes to cancer progression and metastasis. We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells. VIP increased adhesion but decreased expression of metalloproteinases, MMP2 and MMP9, as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells. VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells, suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma. VIP effects in A498 cells were blocked by the VPAC(1/2)-receptor antagonist JV-1-53. In conclusion, present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease.

  13. P2X7 receptor predicts postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma.

    Science.gov (United States)

    Liu, Zheng; Liu, Yidong; Xu, Le; An, Huimin; Chang, Yuan; Yang, Yuanfeng; Zhang, Weijuan; Xu, Jiejie

    2015-09-01

    The P2X7 receptor, an ATP-gated plasma membrane ion channel, is involved in inflammation, apoptosis and cell proliferation, and thereby plays a crucial role during oncogenic transformation in various malignancies. This study aims to evaluate the impact of P2X7 receptor expression on postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma (ccRCC). A total of 273 patients with ccRCC undergoing nephrectomy at a single institution were retrospectively enrolled in this study, among which 86 patients died of this disease and six patients died of other causes. Clinicopathologic features and cancer-specific survival (CSS) were recorded. P2X7 expression was assessed by immunohistochemistry in clinical specimens. Kaplan-Meier method with log rank test was performed to compare survival curves. Cox regression models were used to evaluate the prognostic values of variables on CSS. Concordance index was calculated to assess prognostic accuracy of prognostic models. Median follow-up period was 90 months (range, 11-120 months). Intratumoral P2X7 expression was significantly lower than peritumoral tissues (P independent prognostic factor for CSS (hazard ratio [HR], 1.693; P = 0.034). The prognostic accuracy of TNM stage, UISS and SSIGN scoring models was improved when intratumoral P2X7 expression was added. Intratumoral P2X7 expression is a potential independent adverse prognostic indicator for postoperative CSS of patients with ccRCC. PMID:26179886

  14. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  15. Coexistence of essential thrombocythemia, iron-refractory iron deficiency anemia and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sinem Namdaroğlu

    2016-03-01

    Full Text Available Essential thrombocythemia (ET is a Philadelphia chromosome (Ph-negative myeloproliferative neoplasm. It is characterized by thrombocytosis and megakaryocytic hyperplasia of the bone marrow with JAK2V617F mutation. Iron-refractory iron deficiency anemia (IRIDA is an autosomal recessive disorder, which is mainly characterized by iron deficiency anemia not responding to oral iron intake, but partially responding to parenteral iron therapy. Recently, it has been shown that IRIDA has stemmed from mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (matriptase- 2 expressed by the liver. Renal cell carcinoma (RCC accounts for 2-3% of all cancers. As the most common solid lesion in the kidneys, it represents approximately 90% of all renal malignancies. Approximately 30% of patients with symptomatic RCCs seem to display paraneoplastic syndromes. The symptom that may result from erythrocytosis is the most wellknown paraneoplastic hematological event. Here, we report a patient who presents with coexistence of RCC and thrombocytosis, which hasn’t been caused by hormonal factors that are produced in tumor cells. This patient has been therefore diagnosed with ET. The patient who was expected to display RCC with polycythemia, conversely present with IRIDA.

  16. Application of the revised Tumour Node Metastasis (TNM) staging system of clear cell renal cell carcinoma in eastern China: advantages and limitations

    Institute of Scientific and Technical Information of China (English)

    Chao Qin; Li-Jiang Sun; Li Cui; Qiang Cao; Jian Zhu; Pu Li; Gui-Ming Zhang

    2013-01-01

    This study was designed to evaluate whether the revised 2010 Tumour Node Metastasis (TNM) staging system could lead to a more accurate prediction of the prognosis of renal cell carcinoma (RCC) patients.A total of 1216 patients who had undergone radical nephrectomy or partial nephrectomy for RCC from 2003 to 2011 were enrolled.All of the patients had pathologically confirmed clear cell RCC (ccRCC).All cases were staged by both the 2002 and 2010 TNM staging systems after pathological review,and survival data were collected.Univariate and multivariate Cox regression models were used to evaluate cancer-specific survival (CSS) and progression-free survival (PFS) after surgery.Continuous variables,such as age and tumour diameter,were calculated as mean values and standard deviations (s.d.) or as median values.Survival was calculated by the Kaplan-Meier method,and the log-rank test assessed differences between groups.Statistically significant differences in CSS and PFS were noted among patients in T3 subgroups using the new 2010 staging system.Therefore,the revised 2010 TNM staging system can lead to a more accurate prediction of the prognosis of ccRCC patients.However,when using the revised 2010 staging system,we found that more than 92% of patients (288/313) with T3 tumours were staged in the T3a subgroup,and their survival data were not significantly different from those of patients with T2b tumours.In addition,T2 subclassification failed to independently predict survival in RCC patients.

  17. Major role for a 3p21 region and lack of involvement of the t(3;8) breakpoint region in the development of renal cell carcinoma suggested by loss of heterozygosity analysis

    NARCIS (Netherlands)

    van den Berg, Anke; Hulsbeek, MMF; deJong, D; Kok, K; Veldhuis, PMJF; Roche, J; Buys, CHCM

    1996-01-01

    In a loss of heterozygosity analysis of 3p, we examined 44 sporadic cases of renal cell carcinoma (RCC) and matched normal tissue with 18 markers distributed over the whole p-arm. The majority of these markers clustered in three regions that have been suggested to be involved in the development of R

  18. Small cell undifferentiated carcinoma in the epididymis

    Institute of Scientific and Technical Information of China (English)

    CHEN Jia-wei; YUAN Lin; Hu Hong-hui

    2005-01-01

    @@ Small cell undifferentiated carcinoma is a special type of tumor which is usually found in the lungs. However, it is very rare in extra pulmonary tissues, especially in epididymis. One case of small cell undifferentiated carcinoma in the right epididymis, with partial differentiation to adenocarcinoma and neuroendocrine carcinoma is reported as follows.

  19. Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

    DEFF Research Database (Denmark)

    Sørensen, Anne V.; Donskov, Frede; Hermann, Gregers G.;

    2014-01-01

    AbstractAim To evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC). Methods All Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between...... received first line treatment. From 2006 to 2010 we observed a significant increase in the number of referred patients; a significant increase in treated patients (64% versus 75%, P = 0.0188); a significant increase in first line targeted therapy (22% versus 75%, P ....06–0.60; P = 0.0051) were significantly associated with longer OS. Conclusion This retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients....

  20. 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

  1. Type 1 papillary renal cell carcinoma in a patient with schwannomatosis: Mosaic versus loss of SMARCB1 expression in respectively schwannoma and renal tumor cells.

    Science.gov (United States)

    Hulsebos, Theo J M; Kenter, Susan; Baas, Frank; Nannenberg, Eline A; Bleeker, Fonnet E; van Minkelen, Rick; van den Ouweland, Ans M W; Wesseling, Pieter; Flucke, Uta

    2016-04-01

    In schwannomatosis, germline SMARCB1 or LZTR1 mutations predispose to the development of multiple benign schwannomas. Besides these, other tumors may occur in schwannomatosis patients. We present a 45-year-old male patient who developed multiple schwannomas and in addition a malignant type 1 papillary renal cell carcinoma (pRCC1). We identified a duplication of exon 7 of SMARCB1 on chromosome 22 in the constitutional DNA of the patient (c.796-2246_986 + 5250dup7686), resulting in the generation of a premature stop codon in the second exon 7 copy (p.Glu330*). The mutant SMARCB1 allele proved to be retained in three schwannomas and in the pRCC1 of the patient. Loss of heterozygosity analysis demonstrated partial loss of the wild-type SMARCB1 allele containing chromosome 22, suggesting loss of that chromosome in only a subset of tumor cells, in all four tumors. Immunohistochemical staining with a SMARCB1 antibody revealed a mosaic SMARCB1 expression pattern in the three benign schwannomas, but absence of expression in the malignant tumor cells of the pRCC1. To our knowledge, this difference in SMARCB1 protein expression has not been reported before. We conclude that a germline SMARCB1 mutation may predispose to the development of pRCC1, thereby further widening the spectrum of tumors that can develop in the context of schwannomatosis. PMID:26799435

  2. The many faces of basal cell carcinoma

    OpenAIRE

    Jackson, Robert

    1982-01-01

    Basal cell carcinoma is the most easily cured carcinoma, but because of the many forms it can take, and because it grows so slowly, it can be misdiagnosed or neglected. The author discusses its more common forms and etiologic considerations.

  3. Cloning and functional research of renal cell carci noma related novel gene-G YLZ-R CC1 8

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    After the renal cell carcinoma related novel gene fragment GYLZ-RCC18 was cloned by using suppres sion subtractive hybridization (SSH), we used the SMART RACE technology to clone the full length of GYLZ-RCC18and performed chromosome location by the FISH method.RT-PCR was used to detect the expression of the first read ing frame of GYLZ-RCC18 in different stages and grades of renal cell carcinoma tissue and other tissues. Also we trans fected the antisense oligonucleotide of GYLZ-RCC18 to renal cell carcinoma cell line GRC-1, and analyzed the prolifera tion activity, growth speed, apoptosis and mortality changes in GRC-1. The results show that the full length of GYLZ-RCC18 (GenBank accession No.: BE825133) cDNA is about 3.5 kb long which is located at No. 14 chromosome.GYLZ-RCC18 has a higher expression in higher grades and stages of renal cell carcinoma than in the lower ones. The expression of GYLZ-RCC18 in renal cell carcinoma was much higher than that in normal kidney and other tissues.After transfection of GYLZ-RCC18 antisense oligonucleotide,the mortality of GRC-1 increases evidently, the proliferation activity and growth speed were inhibited remarkably at the same time. Also the antisense oligonucleotide can induce the apoptosis of GRC-1 all through the observation time. Our results indicated that GYLZ-RCC18 is an important novel gene related to renal cell carcinoma. Its overexpression would stimulate the growth and proliferation activity and plays an antidead and antiapoptosis effect in renal cell car cinoma. Transfection of antisense oligonucleotide could in hibit the generation and development of renal cell carcinoma.The study provides a new clue for the research of renal cell carcinoma, and also provides an instruction for special ge netic diagnosis and the therapy of renal cell carcinoma.

  4. Paraffin-embedded tissue is less accurate than frozen section analysis for determining VHL mutational status in sporadic renal cell carcinoma.

    OpenAIRE

    Verhoest, Grégory; Patard, Jean-Jacques; Fergelot, Patricia; Jouan, Florence; Zerrouki, Salim; Dréano, Stéphane; Mottier, Stéphanie; Rioux-Leclercq, Nathalie; Denis, Marc,

    2012-01-01

    International audience INTRODUCTION: Literature controversies exist regarding the prognostic value of VHL mutations. The objective was to compare paraffin-embedded and frozen section specimens for VHL mutations detection and to evaluate the reliability of DNA analysis in formalin-fixed tissues. METHODS: Seventy-six patients with clear cell renal cell carcinoma (RCC) previously assessed for VHL status from frozen samples were included. Seventy-three tumor samples were known to be mutated fo...

  5. Combined blood/tissue analysis for cancer biomarker discovery: application to renal cell carcinoma.

    Science.gov (United States)

    Johann, Donald J; Wei, Bih-Rong; Prieto, DaRue A; Chan, King C; Ye, Xiaying; Valera, Vladimir A; Simpson, R Mark; Rudnick, Paul A; Xiao, Zhen; Issaq, Haleem J; Linehan, W Marston; Stein, Stephen E; Veenstra, Timothy D; Blonder, Josip

    2010-03-01

    A method that relies on subtractive tissue-directed shot-gun proteomics to identify tumor proteins in the blood of a patient newly diagnosed with cancer is described. To avoid analytical and statistical biases caused by physiologic variability of protein expression in the human population, this method was applied on clinical specimens obtained from a single patient diagnosed with nonmetastatic renal cell carcinoma (RCC). The proteomes extracted from tumor, normal adjacent tissue and preoperative plasma were analyzed using 2D-liquid chromatography-mass spectrometry (LC-MS). The lists of identified proteins were filtered to discover proteins that (i) were found in the tumor but not normal tissue, (ii) were identified in matching plasma, and (iii) whose spectral count was higher in tumor tissue than plasma. These filtering criteria resulted in identification of eight tumor proteins in the blood. Subsequent Western-blot analysis confirmed the presence of cadherin-5, cadherin-11, DEAD-box protein-23, and pyruvate kinase in the blood of the patient in the study as well as in the blood of four other patients diagnosed with RCC. These results demonstrate the utility of a combined blood/tissue analysis strategy that permits the detection of tumor proteins in the blood of a patient diagnosed with RCC. PMID:20121140

  6. Relationship study between platelet count and stage and grade of renal cell carcinoma in indoor patients

    Institute of Scientific and Technical Information of China (English)

    Mohammad Salehi; Zahra Panahandeh; Mahsa Olia; Seyedeh Atefeh Emadi

    2009-01-01

    Objective:Thrombocytosis has been reported in many types of malignancies and has been studied as a prognostic factor.The aim of this survey iS to investigate the relation between platelet count and stage and grade of tumor in indoor patients with renal cell carcinoma(RCC)in order to evaluate the prognostic value of thrembocytosis.Methods:In a descriptive and retrospective survey 82 patients treated by radical nephreetomy for RCC were enrolled.In all cases,TNM stage,Fuhrman grade,invasion and platelet count were recorded and entered in SPSS software for analysis.Results:In this study,76 patients (92.7%)with norlnal platelet and 6 patients(7.3%)with thrombocytosis were studied.In this survey there Was no significant correlation between the thrombocytosis and pathological stage in all patients,both genders and various age groups.In addition,the correlation between thrombocytosis and nuclear grade was investigated and a significant correlation between them in all patients and both genders Was found,Finally,there was no significant correlation between thrombocytosis and nuclear grade at various age groups.Conclusion:Prognostic indicators that can accurately predict survival rates in patients with RCC can be used to select those patients most hkdy to benefit from adjuvant therapy.In this survey there was a significant correlation between thrombocytosis and nuclear grade,however,further clinical studies are needed.

  7. 18-F fluorodeoxyglucose uptake in positron emission tomography as a pathological grade predictor for renal clear cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Yoshifumi; Goshima, Satoshi; Kondo, Hiroshi; Watanabe, Haruo; Kawada, Hiroshi; Kawai, Nobuyuki; Tanahashi, Yukichi [Gifu University Hospital, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University Hospital, Department of Radiology, Gifu (Japan); Gifu University Hospital, Department of Radiology Services, Gifu (Japan); Suzui, Natsuko [Gifu University Hospital, Department of Pathology, Gifu (Japan); Hirose, Yoshinobu [Osaka Medical College, Department of Pathology, Osaka (Japan); Matsunaga, Kengo [Kizawa Memorial Hospital, Department of Pathology, Minokamo (Japan); Nishibori, Hironori [Kizawa Memorial Hospital, Department of Radiology, Minokamo (Japan); Bae, Kyongtae T. [University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States)

    2015-10-15

    To evaluate the usefulness of Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18-F FDG-PET/CT) in the prediction of Fuhrman pathological grades of renal clear cell carcinoma (cRCC). This retrospective study was approved by our institutional review board, and written informed consent was waived. Thirty-one patients with pathologically proven cRCC underwent 18-F FDG-PET/CT for tumour staging. Maximum standardized uptake value of cRCC (tumour SUV{sub max}) and mean SUV of the liver and spleen (liver and spleen SUV{sub mean}) were measured by two independent observers. Tumour SUV{sub max}, tumour-to-liver SUV ratio, and tumour-to-spleen SUV ratio were correlated with the pathological grades. Logistic analysis demonstrated that only the tumour-to-liver SUV ratio was a significant parameter for differentiating high-grade (Fuhrman grades 3 and 4) tumours from low-grade (Fuhrman grades 1 and 2) tumours (P = 0.007 and 0.010 for observers 1 and 2, respectively). Sensitivity, specificity, and positive and negative predictive values for detecting tumours of Fuhrman grades 3 and 4 were 64, 100, 100, and 77 %, respectively, for observer 1, and 79, 88, 85, and 83 %, respectively, for observer 2. The tumour-to-liver SUV ratio with 18-F FDG-PET/CT appeared to be a valuable imaging biomarker in the prediction of high-grade cRCC. (orig.)

  8. A novel method to identify pathways associated with renal cell carcinoma based on a gene co-expression network.

    Science.gov (United States)

    Ruan, Xiyun; Li, Hongyun; Liu, Bo; Chen, Jie; Zhang, Shibao; Sun, Zeqiang; Liu, Shuangqing; Sun, Fahai; Liu, Qingyong

    2015-08-01

    The aim of the present study was to develop a novel method for identifying pathways associated with renal cell carcinoma (RCC) based on a gene co-expression network. A framework was established where a co-expression network was derived from the database as well as various co-expression approaches. First, the backbone of the network based on differentially expressed (DE) genes between RCC patients and normal controls was constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The differentially co-expressed links were detected by Pearson's correlation, the empirical Bayesian (EB) approach and Weighted Gene Co-expression Network Analysis (WGCNA). The co-expressed gene pairs were merged by a rank-based algorithm. We obtained 842; 371; 2,883 and 1,595 co-expressed gene pairs from the co-expression networks of the STRING database, Pearson's correlation EB method and WGCNA, respectively. Two hundred and eighty-one differentially co-expressed (DC) gene pairs were obtained from the merged network using this novel method. Pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the network enrichment analysis (NEA) method were performed to verify feasibility of the merged method. Results of the KEGG and NEA pathway analyses showed that the network was associated with RCC. The suggested method was computationally efficient to identify pathways associated with RCC and has been identified as a useful complement to traditional co-expression analysis. PMID:26058425

  9. Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas

    International Nuclear Information System (INIS)

    High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs

  10. Recurrent renal cell carcinoma manifesting as a large intrathoracic fibrotic mass: A case report

    Science.gov (United States)

    KIM, JI HYUN; JEONG, JAE HOON; PARK, SUNG-HYUN; JEONG, JIN SEON; RYU, YOUNG-JOON; SONG, SEO-YOUNG

    2016-01-01

    Renal cell carcinomas (RCCs) have a strong tendency to metastasize, and the most common sites are the lungs, bones and liver. Late recurrence is another feature of the RCC, with lesions appearing ≥10 years after surgical treatment. However, fibrosis has rarely been associated with the disease. The present study reports a case of recurrent RCC that manifested as a fibrotic mass within the thorax. A 48-year-old man presented with dyspnea that had persisted for 3 days. The patient had undergone a right radical nephrectomy for stage II clear cell carcinoma of the kidney 6 years previously. The patient was a current smoker, with a smoking history of 20 pack-years. Chest radiography showed pleural effusion in the right thorax with an egg-sized mass shadow within the right upper lung (RUL) field. Computed tomography (CT) showed a main mass, 7 cm in diameter, within the RUL, with heterogeneous enhancement and multiple nodules of various sizes in the lungs, suggestive of primary lung cancer or metastatic RCC. A CT-guided percutaneous needle aspiration biopsy was obtained from the main mass, but histology revealed dense fibrous tissue without any malignant cells. Positron emission tomography-CT demonstrated an irregular hypermetabolic RUL mass, with a standardized uptake value (SUV) of 5.0, along the right pleura, and small pulmonary nodules (SUV, 2.0). Ultrasound-guided biopsy was attempted for a smaller hypermetabolic pleural nodule and the result was clear cell adenocarcinoma, consistent with the previous renal histology. The present study describes the case, along with a review of the relevant literature. PMID:27313703

  11. Immunotherapy in renal cell carcinoma.

    Science.gov (United States)

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  12. Gastric Large Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    Case: A 63-year-old male presented with unintentional weight loss of 20 pounds over a 4-month duration. He reported loss of appetite, intermittent post-prandial nausea, bloating and early satiety. He also complained of dyspepsia and had been treated for reflux during the previous 2 years. He denied vomiting, dysphagia, odynophagia, abdominal pain, melena, hematochezia, or alterations in bowel habits. Additionally, he denied fevers, night sweats, cough, or dyspnea. He quit smoking 25 years ago, and denied alcohol use. His past medical history was significant for basal cell carcinoma treated with local curative therapy and he was without recurrence on surveillance. Pertinent family history included a paternal uncle with lung cancer at the age of 74. Physical examination was unremarkable except for occult heme-positive stools. Laboratory evaluation revealed elevated liver enzymes (ALT-112, AST-81, AlkPhos-364). CT scan of the chest, abdomen and pelvis showed diffuse heterogeneous liver with extensive nodularity, raising the concern for metastases. Serum tumor-markers: PSA, CEA, CA 19-9, and AFP were all within normal limits. Screening colonoscopy was normal, but esophagogastroduodenoscopy revealed a malignant-appearing ulcerative lesion involving the gastro-esophageal junction and gastric cardia. Pathology confirmed an invasive gastric large cell neuroendocrine carcinoma. Ultrasound-guided fine needle aspiration of a hepatic lesion revealed malignant cells with cytologic features consistent with large-cell type carcinoma and positive immunostaining for synaptophysin favoring neuroendocrine differentiation. A PET-CT demonstrated intense diffuse FDG uptake of the liver, suggesting diffuse hepatic parenchymal infiltration by tumor. There were multiple foci of intense osseous FDG uptake with corresponding osteolytic lesions seen on CT scan. The remaining intra-abdominal and intra-thoracic structures were unremarkable. The patient will receive palliative systemic therapy

  13. Novel three missense mutations observed in Von Hippel-Lindau gene in a patient reported with renal cell carcinoma

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    Pasupuleti Santhosh Kumar

    2013-01-01

    Full Text Available Von Hippel-Lindau (VHL disease is an autosomal dominant hereditary cancer syndrome that predisposes to the development of a variety of benign and malignant tumors, especially cerebellar hemangioblastomas, retinal angiomas and clear-cell renal cell carcinomas (RCC. We have identified of VHL gene using immunohistochemistry in a patient who was diagnosed for RCC. In order to understand the involvement of mutation in the VHL gene exon 1 was amplified and sequenced (accession number: JX 401534. The sequence analysis revealed the presence of novel missense mutations c.194 C>T, c.239 G>A, c.278 G>A, c.319 C>G, c. 337 C > G leading to the following variations p.Ala 65 Val, p.Gly 80 Asp, p.Gly 93 Glu, p.Gln 107 Glu, p.Gln 113 Glu in the protein.

  14. A new method using multiphoton imaging and morphometric analysis for differentiating chromophobe renal cell carcinoma and oncocytoma kidney tumors

    Science.gov (United States)

    Wu, Binlin; Mukherjee, Sushmita; Jain, Manu

    2016-03-01

    Distinguishing chromophobe renal cell carcinoma (chRCC) from oncocytoma on hematoxylin and eosin images may be difficult and require time-consuming ancillary procedures. Multiphoton microscopy (MPM), an optical imaging modality, was used to rapidly generate sub-cellular histological resolution images from formalin-fixed unstained tissue sections from chRCC and oncocytoma.Tissues were excited using 780nm wavelength and emission signals (including second harmonic generation and autofluorescence) were collected in different channels between 390 nm and 650 nm. Granular structure in the cell cytoplasm was observed in both chRCC and oncocytoma. Quantitative morphometric analysis was conducted to distinguish chRCC and oncocytoma. To perform the analysis, cytoplasm and granules in tumor cells were segmented from the images. Their area and fluorescence intensity were found in different channels. Multiple features were measured to quantify the morphological and fluorescence properties. Linear support vector machine (SVM) was used for classification. Re-substitution validation, cross validation and receiver operating characteristic (ROC) curve were implemented to evaluate the efficacy of the SVM classifier. A wrapper feature algorithm was used to select the optimal features which provided the best predictive performance in separating the two tissue types (classes). Statistical measures such as sensitivity, specificity, accuracy and area under curve (AUC) of ROC were calculated to evaluate the efficacy of the classification. Over 80% accuracy was achieved as the predictive performance. This method, if validated on a larger and more diverse sample set, may serve as an automated rapid diagnostic tool to differentiate between chRCC and oncocytoma. An advantage of such automated methods are that they are free from investigator bias and variability.

  15. Analysis of two single nucleotide polymorphisms and loss of heterozygosity detection in the VHL gene in Chinese patients with sporadic renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    LIU Ning; GONG Kan; NA Xi; WU Guan; NA Yan-qun

    2005-01-01

    @@ Renal cell carcinoma (RCC) is the most common malignant tumour in the adult kidney.Recent studies have shown that inactivation of the tumour suppressor gene VHL located in chromosome 3p25-26 region is responsible for sporadic RCCs.1 According to Kundson's two hit theory,the mechanism of inactivation of a tumour suppressor gene involves mutation,hyper-methylation and loss of heterozygosity (LOH).Mutations and hypermethylation of the VHL gene have been well analysed in RCC,but due to the deficiency of specific gene markers in the VHL region,the exact LOH frequency of the VHL gene in RCC is still unknown.Single nucleotide polymorphisms (SNPs) are regarded as the third generation of human gene markers and are appropriate for LOH analysis.We searched the SNP database in the National Centre for Biotechnology Information,and selected two SNP sites located within the VHL gene region as gene markers.We analysed these two SNP sites in 79 Chinese sporadic RCC patients by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) to detect LOH frequency of the VHL gene and analyse the relationship between VHL LOH and the pathological parameters of RCC.

  16. C-reactive protein in patients with advanced metastatic renal cell carcinoma: Usefulness in identifying patients most likely to benefit from initial nephrectomy

    International Nuclear Information System (INIS)

    C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied. We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests. ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0–1 and ≥2). The retrospective design is a limitation of this study. Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC

  17. Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

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    Mijušković Mirjana

    2016-01-01

    Full Text Available Background/Aim. Kidney injury molecule-1 (KIM-1 and aquaporin-1 (AQP-1 are potential early urinary biomarkers of clear renal cell carcinoma (cRCC. The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1 and urinary AQP-1 (uAQP-1 were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr] were significantly greater compared with controls (healthy volunteers (0.210 ± 0.082 ng/mgUcr (p = 0.0227. Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively. The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr compared with the control group (0.202 ± 0.078 ng/mgUcr (p = 0.0014. Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy. [Projekat Ministarstva nauke Republike Srbije, br. III41018

  18. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model

    Science.gov (United States)

    Suarez, Eloah Rabello; Chang, De-Kuan; Sun, Jiusong; Sui, Jianhua; Freeman, Gordon J.; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A.

    2016-01-01

    Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen. PMID:27145284

  19. Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy

    Directory of Open Access Journals (Sweden)

    Slaby Ondrej

    2010-07-01

    Full Text Available Abstract Background MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies have shown altered expression levels of several microRNAs in renal cell carcinoma. Methods We examined the expression levels of selected microRNAs in 38 samples of conventional renal cell carcinoma (RCC and 10 samples of non-tumoral renal parenchyma using TaqMan real-time PCR method. Results The expression levels of miRNA-155 (p Conclusions We have confirmed previous observations obtained by miRNA microarray analysis using standardized real-time PCR method. For the first time, we have identified a prognostic significance of miRNA-106b, which, after validation on a larger group of patients, maybe useful as a promising biomarker in patients with RCC.

  20. Expression of CD44 and P53 in renal cell carcinoma: Association with tumor subtypes

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    Farahnaz Noroozinia

    2014-01-01

    Full Text Available Renal cell carcinoma (RCC is a common malignancy of the kidney and accurate prediction of prognosis is valuable for the design of adjuvant therapy and counseling and effective scheduling of follow-up visits. Molecular genetic investigations of CD44 and P53 in RCC may be helpful in this regard. We studied the CD44 and P53 expressions semi-quantitatively on paraffin-embedded specimens of 64 RCC patients (37 male/27 female who underwent surgery from 2003 to 2008 by immunohistochemistry and analyzed the correlation of P53 and CD44 expression in RCC and outcome. Thirteen of 64 (20.3% specimens were P53 positive, 30/64 (46.9% were CD44 positive and five tumors with positive P53 expressed CD44 protein (P = 0.5. A statistically significant correlation was not found between CD44 and P53 expression (P = 0.5 and age (P = 0.07, sex (P= 0.3, tumor size (P = 0.7, grade (P = 0.23, vascular invasion (P = 1.00 and ureteral invasion (P = 1.00. Furthermore, a significant correlation was not found between P53 expression with age (P = 0.3, sex (P = 0.7, tumor size (P = 0.7, grade (P = 0.1, vascular inva-sion (P = 1.00 and ureteral invasion (P = 1.00. According to our findings, only P53 expression is generally accompanied by non-conventional subtype tumor.

  1. Detection of renal cell carcinoma using neutron time of flight spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Viana, Rodrigo S.; Yoriyaz, Helio, E-mail: rodrigossviana@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Lakshmanan, Manu N.; Agasthya, Greeshma A.; Kapadia, Anuj J. [Duke University Medical Center, Durham, NC, (United States). Ravin Advanced Imaging Labs, Radiology

    2013-07-01

    The diagnosis of renal cell carcinoma (RCC) is challenging because the symptoms accompanying it are not unique to the disease, and can therefore be misdiagnosed as other diseases. Due to this characteristic, detection of renal cancer is incidental most of time, occurring via abdominal radiographic examinations unrelated to the disease. Presently, biopsy, which is invasive and an unpleasant procedure for the patient, is the most commonly used technique to diagnose RCC. In this study, we demonstrate the application of a novel noninvasive technique for detecting and imaging RCC in vivo. The elemental composition of biological tissues including kidneys has been investigated using a new technique called Neutron Stimulated Emission Computed Tomography (NSECT). This technique is based on detecting the energy signature emitted by the stable isotopes of elements in the body, which are stimulated to emit gamma radiation via inelastic neutron scattering. Methods for improving detection sensitivity and reducing dose, such as time-of-flight neutron spectroscopy have been explored. MCNP5 simulations were used to model the NSECT scanning of the human kidney where the energy and time of arrival of gamma photons were recorded in an ideal detector placed around the human torso. A 5 MeV collimated neutron beam was used to irradiate the kidney containing an RCC lesion. The resulting spectra were resolved in 100 picosecond and 1 keV time and energy bins, respectively. The preliminary results demonstrate the ability to localize the lesion through neutron time of flight spectroscopy and generate a tomographic image at a low dose to the patient. (author)

  2. Intraoperative EBRT and resection for renal cell carcinoma. Twenty-year outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, F.A. [Hospital Gneral Universitario Gregorio Maranon, Madrid (Spain). Dept. of Oncology; Complutense Univ., Madrid (Spain). School of Medicine; Sole, C.V. [Hospital Gneral Universitario Gregorio Maranon, Madrid (Spain). Dept. of Oncology; Complutense Univ., Madrid (Spain). School of Medicine; Instituto de Radiomedicina, Santiago (Spain). Service of Radiation Oncology; Martinez-Monge, R.; Aristu, J. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Radiation Oncology; Azinovic, I. [Hospital de San Jaime, Torrevieja (Spain). Dept. of Radiation Oncology; Zudaire, J.; Berian, J.M. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Urology; Garcia-Sabrido, J.L. [Hospital General Universitario Gregorio Maranon, Madrid (Spain). Dept. of General Surgery

    2013-02-15

    Purpose: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. Patients and methods: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. Results: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. Conclusion: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation. (orig.)

  3. Fibre intake and renal cell carcinoma: a case-control study from Italy.

    Science.gov (United States)

    Galeone, Carlotta; Pelucchi, Claudio; Talamini, Renato; Negri, Eva; Montella, Maurizio; Ramazzotti, Valerio; Zucchetto, Antonella; Dal Maso, Luigino; Franceschi, Silvia; La Vecchia, Carlo

    2007-10-15

    Only 2 previous studies, conducted in Australia, United States and northern Europe, considered the role of dietary fibre intake on renal cell carcinoma (RCC) risk, and both showed a modest, inverse association. Therefore, we investigated in depth the topic of fibres and RCC, using data from a multicenter case-control study conducted in Italy from 1992 to 2004, including 767 cases with incident, histologically confirmed RCC and 1,534 controls admitted to the same network of hospitals as cases with acute nonmalignant conditions. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained after allowance for major identified confounding factors, including total energy intake. The continuous OR for an increase in intake equal to the difference between the 80th and the 20th percentile were 0.94 (95% CI: 0.82-1.08) for total dietary fibre, 0.98 (95% CI: 0.85-1.13) for soluble noncellulose polysaccharides, 0.92 (95% CI: 0.80-1.05) for total insoluble fibre, 0.90 (95% CI: 0.78-1.04) for cellulose, 0.95 (95% CI: 0.84-1.06) for insoluble noncellulose polysaccharides and 1.06 (95% CI: 0.93-1.21) for lignin. With reference to the sources of fibre, we found an inverse association with vegetable fibre (OR = 0.84, 95% CI: 0.73-0.97), but no association with fruit (OR = 0.98, 95% CI: 0.86-1.12) and grain fibre (OR = 1.05, 95% CI: 0.95-1.15). The inverse association with vegetable fibre may reflect a real favorable effect, or be an indicator of a beneficial role of a diet rich in vegetable on RCC risk. PMID:17582601

  4. Elevated expression of stromal palladin predicts poor clinical outcome in renal cell carcinoma.

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    Vivekanand Gupta

    Full Text Available The role that stromal renal cell carcinoma (RCC plays in support of tumor progression is unclear. Here we sought to determine the predictive value on patient survival of several markers of stromal activation and the feasibility of a fibroblast-derived extracellular matrix (ECM based three-dimensional (3D culture stemming from clinical specimens to recapitulate stromal behavior in vitro. The clinical relevance of selected stromal markers was assessed using a well annotated tumor microarray where stromal-marker levels of expression were evaluated and compared to patient outcomes. Also, an in vitro 3D system derived from fibroblasts harvested from patient matched normal kidney, primary RCC and metastatic tumors was employed to evaluate levels and localizations of known stromal markers such as the actin binding proteins palladin, alpha-smooth muscle actin (α-SMA, fibronectin and its spliced form EDA. Results suggested that RCCs exhibiting high levels of stromal palladin correlate with a poor prognosis, as demonstrated by overall survival time. Conversely, cases of RCCs where stroma presents low levels of palladin expression indicate increased survival times and, hence, better outcomes. Fibroblast-derived 3D cultures, which facilitate the categorization of stromal RCCs into discrete progressive stromal stages, also show increased levels of expression and stress fiber localization of α-SMA and palladin, as well as topographical organization of fibronectin and its splice variant EDA. These observations are concordant with expression levels of these markers in vivo. The study proposes that palladin constitutes a useful marker of poor prognosis in non-metastatic RCCs, while in vitro 3D cultures accurately represent the specific patient's tumor-associated stromal compartment. Our observations support the belief that stromal palladin assessments have clinical relevance thus validating the use of these 3D cultures to study both progressive RCC

  5. Outcome and Safety of Sorafenib in Metastatic Renal Cell Carcinoma Dialysis Patients: A Systematic Review.

    Science.gov (United States)

    Leonetti, Alessandro; Bersanelli, Melissa; Castagneto, Bruno; Masini, Cristina; Di Meglio, Giovanni; Pellegrino, Benedetta; Buti, Sebastiano

    2016-08-01

    Few data are available about sorafenib use in patients with metastatic renal cell carcinoma (mRCC) undergoing hemodialysis. No systematic review has been previously performed about this issue. The objective of the present review is to investigate pharmacokinetics and clinical outcomes of sorafenib in mRCC patients undergoing hemodialysis. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, all the literature about mRCC dialysis patients receiving sorafenib, published from January 1946 to August 2015, was evaluated. Applying inclusion/exclusion criteria, 11 articles were selected for the analysis; 1 patient from our department was also included. The investigated outcomes were pharmacokinetics, toxicity, response rate, progression-free survival, and overall survival where available. A total of 36 patients were included. Median treatment duration was 6.0 months on overall population; median progression-free survival was 6.3 months (calculated on 19 patients); response rate was 22% (on 29 patients); median overall survival was 14.9 months (on 28 patients). Of note, 24 patients started sorafenib at reduced dose; 6 of 36 patients (17%) required dose reduction due to adverse events (AEs). Sorafenib treatment was discontinued in 7 patients (19%) because of AEs. Most of AEs were Grade 1-2; severe toxicities (Grade 4-5) included G4 anemia (1 case), G4 hypertension (1 case), G4 cerebellar hemorrhage (1 patient), and a case of G5 subarachnoid hemorrhage. This review confirmed the efficacy of sorafenib treatment in mRCC patients receiving hemodialysis. Nevertheless, drug toxicity seems to be increased in these patients, despite the initiation of therapy at reduced doses; therefore, sorafenib should be used with caution in dialysis patients. PMID:26899142

  6. Lingual metastasis from renal cell carcinoma: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Camillo Porta

    2012-06-01

    Full Text Available Renal cell carcinoma (RCC accounts for the 3% of all solid tumors. Despite continuous improvement in the therapy regimen, less has been achieved in terms of enabling an earlier diagnosis: the neoplasia usually reveals its presence at an advanced stage, obviously affecting prognosis. The most frequent sites of secondary disease are shown to be lungs (50-60%, bone (30-40%, liver (30-40% and brain (5%; while the head and neck district seems to account for less than 1% of patients with primary kidney lesion. We report here the case of a 70-year old man who presented with acute renal failure due to abdominal recurrence of RCC 18 years post nephrectomy. After a few months of follow up without any systemic therapy due to the renal impairment, the patient presented a vascularized tongue lesion that was demonstrated to be a secondary localization of the RCC. This lesion has, therefore, been treated with microsphere embolization to stop the frequent bleeding and to lessen the unbearable concomitant symptoms it caused, such as dysphagia and pain. A tongue lesion that appears in a RCC patient should always be considered suspect and a multidisciplinary study should be conducted both to assess whether it is a metastasis or a primary new lesion and to understand which method should be selected, if necessary, to treat it (surgery, radiation or embolization. Lingual metastasis should be examined accurately not only because they seem to implicate a poor prognosis, but also because they carry a burden of symptoms that not only threatens patients’ lives but also has a strong impact on their quality of life.

  7. Small cell glioblastoma or small cell carcinoma

    DEFF Research Database (Denmark)

    Hilbrandt, Christine; Sathyadas, Sathya; Dahlrot, Rikke H;

    2013-01-01

    was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed...

  8. Network spatio-temporal analysis predicts disease stage-related genes and pathways in renal cell carcinoma.

    Science.gov (United States)

    Li1, X H; Yang, C Z; Wang, J

    2016-01-01

    The purpose of this study was to screen the key genes and pathways of renal cell carcinoma (RCC) and lay the foundation for its diagnosis and therapy. Microarray data of normal subjects and RCC patients at different stages of disease were used to screen differentially expressed genes (DEGs). Based on the DEGs in the four disease stages, four co-expression networks were constructed using the Empirical Bayes method and hub genes were obtained by centrality analysis. The enriched pathways of the DEGs and the mutual hub genes in the cluster of each disease stage were investigated. The mutual hub genes of the four disease stages in RCC tissue were validated using reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. A total of 432 DEGs were screened, including 233 upregulated and 199 downregulated genes, by statistical analysis. Centrality analysis of co-expression networks in different disease stages suggested that PLXDC1, IKZF1, RUNX2, and RNF125 were mutual hub genes. Pathway analysis showed that the DEGs were significantly enriched in seven terms. The hub modules in stage I disease were significantly enriched in the complement coagulation cascade pathway and the hub modules of the other three disease stages were enriched in natural killer cell-mediated cytotoxicity. The expression levels of PLXDC1, IKZF1, RUNX2, and RNF125 were significantly different between normal subjects and RCC patients by RT-PCR and western blot. Our study revealed four hub genes (PLXDC1, IKZF1, RUNX2, and RNF125) and two biological pathways that might be underlying biomarkers involved in RCC. PMID:27173324

  9. Scalp squamous cell carcinoma in xeroderma pigmentosum

    OpenAIRE

    Awan, Basim A; Hanadi Alzanbagi; Osama A Samargandi; Hossam Ammar

    2014-01-01

    Context: Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Case Report: Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child...

  10. Synchronous Squamous Cell Carcinoma in Multiple Digits

    OpenAIRE

    Abner, Sabra; Redstone, Jeremiah; Chowdhry, Saeed; Kasdan, Morton L.; Wilhelmi, Bradon J.

    2011-01-01

    Cancers of the perionychium are relatively rare occurrences and are often related to chronic inflammation associated with trauma, infection, exposure to ultraviolet radiation, or other carcinogens. Squamous cell carcinoma is the most common tumor reported of the nail bed. Synchronous squamous cell carcinomas of the perionychium have been rarely reported. We present a case of a 46-year-old woman with synchronous squamous cell carcinomas involving both hands and multiple digits. Treatment modal...

  11. Merkel Cell Carcinoma Concurrent with Bowen's Disease

    OpenAIRE

    Park, Hyun Chul; Kang, Ho Song; Park, Kyoung Tae; Oh, Young Ha; Yu, Hee Joon; Kim, Joung Soo

    2012-01-01

    Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the elderly and immunocompromised patients. It is occasionally found coexisting with other diseases, such as squamous cell carcinoma, basal cell carcinoma, actinic keratosis, miscellaneous adnexal tumors, and rarely Bowen disease. A 75-year-old woman presented with a 6-month history of an irregularly shaped erythematous patch on the left mandibular angle. Three months later, a 1.5×1.0 cm sized painless and rapidly growi...

  12. Neglected Giant Scalp Basal Cell Carcinoma

    OpenAIRE

    Anne Kristine Larsen, MD; Waseem-Asim Ghulam El-Charnoubi, MD; Julie Gehl, MD, PhD; Christen Krag, MD, PhD

    2014-01-01

    Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstruct...

  13. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  14. Erythropoietin production in renal cell carcinoma and renal cysts in autosomal dominant polycystic kidney disease in a chronic dialysis patient with polycythemia: A case report

    OpenAIRE

    Ito, Keiichi; Asano, Takako; TOMINAGA, SUSUMU; Yoshii, Hidehiko; SAWAZAKI, HARUTAKE; ASANO, TOMOHIKO

    2014-01-01

    In patients undergoing chronic hemodialysis (HD), erythropoietin (EPO) production from the kidney generally decreases and renal anemia develops. Patients without anemia, but with high serum EPO (sEPO) levels are rare among HD patients. The current study presents the case of a 67-year-old female HD patient with autosomal dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC), manifesting polycythemia with elevated sEPO levels. A radical nephrectomy was performed, which dimin...

  15. Metastatic Renal Cell Carcinoma to the Thyroid Gland: A Case Report and Brief Review of the Literature

    Directory of Open Access Journals (Sweden)

    Georgios Kyriakos

    2014-06-01

    Full Text Available Thyroid metastases are rarely seen in clinical practice but should be considered particularly in patients with a history of non-thyroidal malignancies. Renal cell carcinoma (RCC is the most common tumor to metastasize to the thyroid gland and may present many years after a nephrectomy. Thus, patients require a long-term follow-up and, physicians should have a high index of suspicion particularly in patients with benign disorders of the thyroid gland. Fine needle aspiration cytology (FNAC and thyroglobulin immunohistochemical staining are considered the most effective methods for diagnosis. Surgical treatment of solitary thyroid metastases is recommended and prolongs survival. Adjuvant medical treatment may also be useful in specific situations. We present the unusual case of a relative young patient with goiter who presented with an intrathyroidal metastasis of RCC. Turk Jem 2014; 2: 58-60

  16. Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

    Science.gov (United States)

    Mlcochova, Hana; Machackova, Tana; Rabien, Anja; Radova, Lenka; Fabian, Pavel; Iliev, Robert; Slaba, Katerina; Poprach, Alexandr; Kilic, Ergin; Stanik, Michal; Redova-Lojova, Martina; Svoboda, Marek; Dolezel, Jan; Vyzula, Rostislav; Jung, Klaus; Slaby, Ondrej

    2016-01-01

    Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro. PMID:27549611

  17. Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.

    Directory of Open Access Journals (Sweden)

    Magdalena B Wozniak

    Full Text Available Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05 mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA project and identified 60% (402 of the downregulated and 74% (469 of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.

  18. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review.

    Science.gov (United States)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-06-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis. PMID:27398205

  19. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne – case report and literature review

    OpenAIRE

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P.

    2016-01-01

    Key Clinical Message Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment‐resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.

  20. Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Xue-song; ZHANG Zheng; ZHANG Qian; WANG Gang; HE Zhi-song; ZHOU Li-quan; JIN Jie; WU Xiang; ZHAO Peng-ju; HUANG Li-hua; SONG Yi; GONG Kan; SHEN Cheng YU Wei; SONG Gang; ZHAO Zheng

    2011-01-01

    Background The tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.Methods A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level.Results The median follow-up was 15 months (10 cycles, range 1.5-30.0 months (1-20 cycles)). Ten patients (29.4%)achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting >2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0-28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7-24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival

  1. 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.

  2. Merkel cell carcinoma versus metastatic small cell primary bronchogenic carcinoma

    Directory of Open Access Journals (Sweden)

    Katya Lisette Velasquez Cantillo

    2013-01-01

    Full Text Available Merkel cell carcinoma (MCC of the skin is a rare, aggressive, malignant neuroendocrine neoplasm. The tumor classically demonstrates positive immunohistochemistry (IHC staining for chromogranin A(ChrA, cytokeratin 20 (CK20, neuron specific enolase (NSE and/or achaete-acute complex-like 1 (MASH1. The newly identified Merkel cell polyomavirus (MCPyV has been found to be associated with most MCC cases. The primary histologic differential diagnoses of cutaneous MCC is small cell primary bronchogenic carcinoma (SCLC; moreover, both are of neuroendocrine origin. SCLC accounts for approximately 10-15% of all primary lung cancer cases; this histologic subtype is a distinct entity with biological and oncological features distinct from non-small cell lung cancer (NSCLC. In contradistinction to MCC, SCLC is classically IHC positive for cytokeratin 7 (CK7 and transcription factor (TTF-1. Similar to SCLC, MCC cell lines may be classified into two different biochemical subgroups designated as Classic and Variant. In our review and case report, we aim to emphasize the importance of a multidisciplinary approach to the approach to this difficult differential diagnosis. We also aim to comment about features of the cells of origin of MCC and SCLC; to summarize the microscopic features of both tumors; and to review their respective epidemiologic, clinical, prognostic and treatment features. We want to emphasize the initial workup study of the differential diagnosis patient, including evaluating clinical lymph nodes, a clinical history of any respiratory abnormality, and chest radiogram. If a diagnosis of primary cutaneous MCC is confirmed, classic treatment includes excision of the primary tumor with wide margins, excision of a sentinel lymph node, and computed tomography, positron emission tomography and/or Fluorine-18-fluorodeoxyglucose positron emission tomography scan studies

  3. Characterization of N-diethylnitrosamine-initiated and ferric nitrilotriacetate-promoted renal cell carcinoma experimental model and effect of a tamarind seed extract against acute nephrotoxicity and carcinogenesis.

    Science.gov (United States)

    Vargas-Olvera, Chabetty Y; Sánchez-González, Dolores Javier; Solano, José D; Aguilar-Alonso, Francisco A; Montalvo-Muñoz, Fernando; Martínez-Martínez, Claudia María; Medina-Campos, Omar N; Ibarra-Rubio, María Elena

    2012-10-01

    Renal cell carcinoma (RCC), the commonest malignancy in adult kidney, lacks of early signs, resulting often in metastasis at first diagnosis. N-Diethylnitrosamine (DEN)-initiated and ferric nitrilotriacetate (FeNTA)-promoted RCC may be a useful experimental model, but it is not well characterized. In this study, histological alterations and oxidative stress markers were analyzed at different times throughout RCC development, histological subtype was re-evaluated in the light of current classification, and a tamarind seed extract (TSE) effect was examined. Male Wistar rats experimental groups were control, TSE, DEN, DEN+FeNTA, and TSE+DEN+FeNTA. TSE was given 2 weeks before DEN administration (200 mg/kg) and throughout the experiment. Fourteen days after DEN treatment, two FeNTA doses (9 mg Fe/kg) for acute nephrotoxicity study, and increasing FeNTA doses (3-9 mg Fe/kg) twice a week for 16 weeks for carcinogenesis protocol, were administered. In acute study, necrosis and renal failure were observed and TSE ameliorated them. Throughout carcinogenesis protocol, preneoplastic lesions were observed since 1 month of FeNTA treatment, which were more evident at 2 months, when also renal cysts and RCC were already detected. RCC tumors were obtained without changes in renal function, and clear cell histological subtype was identified in all cases. 4-Hydroxy-2-nonenal and 3-nitro-L: -tyrosine levels increased progressively throughout protocol. TSE decreased both oxidative stress markers and, although there was no statistical difference, it delayed RCC progress and decreased its incidence (21 %). This study brings an insight of the time course events in this carcinogenesis model, identifies clear cell subtype and establishes TSE renoprotective effects.

  4. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma*

    Science.gov (United States)

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado Filho, Carlos D'Apparecida Santos

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  5. Comprehensive analysis of 5-aminolevulinic acid dehydrogenase (ALAD variants and renal cell carcinoma risk among individuals exposed to lead.

    Directory of Open Access Journals (Sweden)

    Dana M van Bemmel

    Full Text Available BACKGROUND: Epidemiologic studies are reporting associations between lead exposure and human cancers. A polymorphism in the 5-aminolevulinic acid dehydratase (ALAD gene affects lead toxicokinetics and may modify the adverse effects of lead. METHODS: The objective of this study was to evaluate single-nucleotide polymorphisms (SNPs tagging the ALAD region among renal cancer cases and controls to determine whether genetic variation alters the relationship between lead and renal cancer. Occupational exposure to lead and risk of cancer was examined in a case-control study of renal cell carcinoma (RCC. Comprehensive analysis of variation across the ALAD gene was assessed using a tagging SNP approach among 987 cases and 1298 controls. Occupational lead exposure was estimated using questionnaire-based exposure assessment and expert review. Odds ratios (OR and 95% confidence intervals (CI were calculated using logistic regression. RESULTS: The adjusted risk associated with the ALAD variant rs8177796(CT/TT was increased (OR = 1.35, 95%CI = 1.05-1.73, p-value = 0.02 when compared to the major allele, regardless of lead exposure. Joint effects of lead and ALAD rs2761016 suggest an increased RCC risk for the homozygous wild-type and heterozygous alleles ((GGOR = 2.68, 95%CI = 1.17-6.12, p = 0.01; (GAOR = 1.79, 95%CI = 1.06-3.04 with an interaction approaching significance (p(int = 0.06. No significant modification in RCC risk was observed for the functional variant rs1800435(K68N. Haplotype analysis identified a region associated with risk supporting tagging SNP results. CONCLUSION: A common genetic variation in ALAD may alter the risk of RCC overall, and among individuals occupationally exposed to lead. Further work in larger exposed populations is warranted to determine if ALAD modifies RCC risk associated with lead exposure.

  6. Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

    International Nuclear Information System (INIS)

    The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0-16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (> 25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC

  7. Squamous Cell Carcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Andre Luiz De Souza

    2014-11-01

    Full Text Available We previously published our and Johns Hopkins data titled: "Platinum-based therapy in adenosquamous pancreatic cancer: experience at two institutions” [1]. We will here like to submit a related case report as a letter to the editor to JOP in reference to the above paper. Squamous cell carcinoma of the pancreas has various reported incidence rates, ranging from 0.5% to as high as 5% of pancreatic ductal carcinomas [2, 3]. Of the 1300 cases of pancreatic cancers observed at autopsy in a survey in Japan in 1992, 0.7% were squamous cell carcinoma [4]. A Mayo clinic review of very rare exocrine tumors showed an even rarer incidence of squamous cell carcinoma when compared to acinar and small cell carcinoma of the pancreas [5]. This discrepancy in the reported incidence rates related to the fact that some of the cases represent adenosquamous carcinoma rather than pure squamous cell carcinoma of pancreas. In an analysis of 25 patients, mean age at diagnosis of pancreatic squamous cell carcinoma was 62 years (range: 33–80 years and there was no gender difference [6]. There is no study about the molecular profile of squamous carcinoma of the pancreas. There are no retrospective or prospective studies about the best therapy for these tumors

  8. The Expression of p53 and Cox-2 in Basal Cell Carcinoma, Squamous Cell Carcinoma and Actinic Keratosis Cases

    OpenAIRE

    Ülker KARAGECE YALÇIN; Selda SEÇKİN

    2012-01-01

    Objective: The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship.Material and Method: 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostainin...

  9. Acinar Cell Carcinoma of the Pancreas

    Institute of Scientific and Technical Information of China (English)

    Hua Li; Qiang Li

    2008-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor which is defined as a carcinoma that exhibits pancreatic enzyme production by neoplastic cells. This review includes re-cent developments in our understanding of the epidemiology and pathogenesis of ACC, imaging and pathological diagnosis and ap-proaches to treatment with reference to the literature.

  10. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  11. Fabrication of mAb G250-SPIO molecular magnetic resonance imaging nanoprobe for the specific detection of renal cell carcinoma in vitro.

    Directory of Open Access Journals (Sweden)

    Cailuan Lu

    Full Text Available Molecular magnetic resonance imaging (mMRI has been paid more and more attention for early diagnosis of cancer. A sensitive and specific mMRI probe plays the most important role in this technique. In this study, superparamagnetic iron oxide (SPIO nanoparticles and mAb G250 were conjugated as mMRI probe for the detection of clear cell renal cell carcinoma (ccRCC using 3.0-Tesla MRI in vitro. mAb G250 could specifically recognize carbonic anhydrase IX (CAIX antigen overexpressed in ccRCC and the SPIO nanoparticles as MRI contrast agent presented excellent MRI response and good biocompatibility. The successful assembly of this nanoprobe was confirmed by UV-vis spectrum, FT-IR spectroscopy and DLS analysis. In vitro MRI study on ccRCC cells and control cells indicated that our fabricated mAb G250-SPIO nanoprobe could be used in the specific labeling of clear cell renal carcinoma cells successfully.

  12. Xenotransplanted human prostate carcinoma (DU145) cells develop into carcinomas and cribriform carcinomas: ultrastructural aspects.

    Science.gov (United States)

    Gilloteaux, Jacques; Jamison, James M; Neal, Deborah R; Summers, Jack L; Taper, Henryk S

    2012-10-01

    Androgen-independent, human prostate carcinoma cells (DU145) develop into solid, carcinomatous xenotransplants on the diaphragm of nu/nu mice. Tumors encompass at least two poorly differentiated cell types: a rapidly dividing, eosinophilic cell comprises the main cell population and a few, but large basophilic cells able to invade the peritoneal stroma, the muscular tissue, lymph vessels. Poor cell contacts, intracytoplasmic lumina, and signet cells are noted. Lysosomal activities are reflected by entoses and programmed cell deaths forming cribriform carcinomas. In large tumors, degraded cells may align with others to facilitate formation of blood supply routes. Malignant cells would spread via ascites and through lymphatics.

  13. Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

    Directory of Open Access Journals (Sweden)

    Marcelo Zerati

    2013-07-01

    Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

  14. Immunotherapeutic strategies for the treatment of renal cell carcinoma: where are we now?

    Science.gov (United States)

    Bedke, Jens; Stenzl, Arnulf

    2013-12-01

    Immunotherapy with cytokines was the first effective treatment in metastatic renal cell carcinoma (mRCC). Long-term responders and complete remissions were observed, but efficacy in the overall population was limited with the consequence that targeted agents replaced cytokines. The discovery of tumor associated antigens as direct targets paved the way from theses rather unspecific to specific immunotherapeutic strategies, which are discussed in this review. Autologous or dendritic cell (DC) based tumor vaccination with vitespen or AGS-003, adoptive T-cell transfer and synthetic peptide vaccination with IMA901 are new and promising approaches. Besides that the more passive strategies of antibody dependent cytotoxicity with the VEGF antibody bevacizumab or the carbonic anhydrase IX antibody girentuximab are discussed. Immunomodulation by cyclophosphamide, tyrosine kinase inhibitors or nivolumab, which targets the PD-1 axis, further promote T-cell activation and combinatory strategies with these agents are outlined.

  15. The early response of renal cell carcinoma to tyrosine kinase inhibitors evaluated by FDG PET/CT was not influenced by metastatic organ

    International Nuclear Information System (INIS)

    Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for advanced renal cell carcinoma (RCC), but it has been unclear whether the antitumor effect of TKIs depends on the organ where the RCC metastasis is located. We previously reported that the FDG accumulation assessed by FDG PET/CT, was a powerful index for evaluating the biological response to TKI. In this study we investigated the differences in FDG accumulation and the response to TKI as assessed by FDG PET/CT among various organs where RCC were located. A total of 48 patients with advanced RCC treated with a TKI (25 with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at 1 month after a TKI treatment initiation. The maximum standardized uptake value (SUVmax) of all RCC lesions were measured and analyzed. We evaluated 190 RCC lesions. The pretreatment SUVmax values (mean ± SD) were as follows: in the 49 lung metastases, 4.1 ± 3.3; in the 40 bone metastases, 5.4 ± 1.6; in the 37 lymph node metastases, 6.7 ± 2.7; in the 29 abdominal parenchymal organ metastases, 6.6 ± 2.7; in the 26 muscle or soft tissue metastases, 4.4 ± 2.6; and in the nine primary lesions, 8.9 ± 3.9. Significant differences in the SUVmax were revealed between metastases and primary lesions (p = 0.006) and between lung metastases and non-lung metastases (p < 0.001). The SUVmax change ratios at 1 month after TKI treatment started were -14.2 ± 48.4% in the lung metastases, -10.4 ± 23.3% in the bone metastases, -9.3 ± 47.4% in the lymph node metastases, -24.5 ± 41.7% in the abdominal parenchymal organ metastases, -10.6 ± 47.4% in the muscle or soft tissue metastases, and -24.2 ± 18.3% in the primary lesions. There was no significant difference among the organs (p = 0.531). The decrease ratio of FDG accumulation of RCC lesions evaluated by PET/CT at 1 month after TKI treatment initiation was not influenced by the organs where the RCC metastasis was located. This result suggests that TKIs can

  16. Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens

    Science.gov (United States)

    Baine, Marina K.; Turcu, Gabriela; Zito, Christopher R.; Adeniran, Adebowale J.; Camp, Robert L.; Chen, Lieping

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites. Utilizing a quantitative immunofluorescence technique, TIL subsets were examined in matched primary and metastatic specimens. In metastatic specimens, we found an association between low CD8+ to Foxp3+ T-cell ratios and high levels of PD-L1. High PD-L1-expressing metastases were also found to be associated with tumors that were high in both CD4+ and Foxp3+ T-cell content. Taken together these results provide the basis for combining agents that target the PD-1/PD-L1 pathway with agonist of immune activation, particularly in treating RCC metastases with unfavorable tumor characteristics and microenvironment. In addition, CD8+ TIL density and CD8:Foxp3 T-cell ratio were higher in primary than metastatic specimens, supporting the need to assess distant sites for predictive biomarkers when treating disseminated disease. PMID:26317902

  17. CYTOGENETIC ANALYSIS OF EPITHELIAL RENAL-CELL TUMORS - RELATIONSHIP WITH A NEW HISTOPATHOLOGICAL CLASSIFICATION

    NARCIS (Netherlands)

    VANDENBERG, E; VANDERHOUT, AH; OOSTERHUIS, JW; STORKEL, S; DIJKHUIZEN, T; ZWEERS, HMM; MENSINK, HJA; BUYS, CHCM; DEJONG, B; Dam, A.

    1993-01-01

    Renal-cell carcinomas (RCC) are clinically, histologically and cytogenetically very heterogeneous. The present histological WHO classification shows no clear correlation between histologic subtypes and specific chromosomal abnormalities. In 1986, a new classification was proposed by Thoenes and Stor

  18. Gender Specific Mutation Incidence and Survival Associations in Clear Cell Renal Cell Carcinoma (CCRCC.

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    Christopher J Ricketts

    Full Text Available Renal cell carcinoma (RCC is diagnosed in >200,000 individuals worldwide each year, accounting for ~2% of all cancers, but the spread of this disease amongst genders is distinctly uneven. In the U.S. the male:female incidence ratio is approximately 2:1. A potential hypothesis is mutation spectra may differ between tumors dependent upon the gender of the patient, such as mutations of X chromosome encoded genes being more prevalent in male-derived tumors. Combined analysis of three recent large-scale clear cell renal cell carcinoma (CCRCC mutation sequencing projects identified a significantly increased mutation frequency of PBRM1 and the X chromosome encoded KDM5C in tumors from male patients and BAP1 in tumors from female patients. Mutation of BAP1 had previously been significantly associated with poorer overall survival; however, when stratified by gender, mutation of BAP1 only significantly affected overall survival in female patients. Mutation of chromatin remodeling genes alters gene regulation, but the overall effect of these alterations may also be modified by the presence of other gender specific factors. Thus, the combination of gender and mutation of a specific gene, such as BAP1, may have implications not only for prognosis but also for understanding the role of chromatin remodeling gene mutations in kidney cancer progression.

  19. Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs. The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC. The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients. To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC

  20. Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents. Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment. Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034). Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM

  1. Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Vogl Ursula M

    2010-09-01

    Full Text Available Abstract Background In the era of cytokines, patients with brain metastases (BM from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA have improved the outcome of patients with metastatic renal cell carcinoma (mRCC however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents. Methods Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR, progression free survival (PFS and overall survival (OS. All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment. Results Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC patients (10.5% were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3 and 11.4 months (95% CI 8.7 - 14.1 for BM-patients and non-BM-patients, respectively (p = 0.232. The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9 and 33.3 months (95% CI 18.6 - 47.0 (p = 0.358, respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034. Conclusions Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.

  2. DNA甲基化在肾癌诊治的应用%Application of DNA methylation in diagnosis and treatment of renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    范博; 张开立; 张亮

    2011-01-01

    The formation of renal cell carcinoma (RCC) is a complicated process including a large number of gene modifications. There are two key mechanisms in this process; ①Genetics of RCC-mutation formation by means of DNA nucleotide sequences alteration ;②Epigenetics of RCC-the levels of genes change through base modification without DNA nucleotide sequences alteration. As the major member of epigenetic family, abnormal DNA methylation can induce the RCC occurrence through influencing the transcription of RCC associated genes. Now we summarizes the roles of DNA methylation in clinical diagnosis, treatment, prognosis and pathologic staging of RCC.%肾癌的发生与形成是多基因改变的复杂过程,而参与其中的机制主要有2类:①遗传学机制,即通过DNA核苷酸序列改变而形成突变,引起肿瘤形成;②表观遗传学机制,即在DNA核苷酸序列不变的情况下,通过碱基修饰而引起基因水平的变化.作为表观遗传学家族中的重要成员,DNA甲基化程度的异常变化可影响肾癌相关基因的转录,从而影响肾癌的发生.现对DNA甲基化在肾细胞癌中的早期诊断、治疗靶点、预后监测和病理分期等临床应用作一综述.

  3. Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma

    International Nuclear Information System (INIS)

    Hepcidin has an important role in iron metabolism. We investigated whether hepcidin was involved in renal cell carcinoma (RCC). We measured serum hepcidin-25 levels in 32 patients by liquid chromatograpy (LC)-mass spectrometry (MS)/MS, and assessed hepcidin mRNA expression in paired tumor and non-tumor tissue samples from the surgical specimens of 53 consecutive patients with RCC by real-time reverse transcription polymerase chain reaction. The serum hepcidin-25 level was higher in patients with metastatic RCC than nonmetastatic RCC (P < 0.0001), and was positively correlated with the serum interleukin-6 and C-reactive protein levels (P < 0.001). Expression of hepcidin mRNA was lower in tumor tissues than in non-tumor tissues (P < 0.0001). The serum hepcidin-25 level was not correlated with the expression of hepcidin mRNA in the corresponding tumor tissue specimens from 32 patients. Hepcidin mRNA expression in tumor tissue was correlated with metastatic potential, but not with histological differentiation or tumor stage. Kaplan-Meier analysis showed that over expression of hepcidin mRNA was related to shorter overall survival in RCC patients. Univariate analysis (Cox proportional hazards model) showed that the hepcidin mRNA level was an independent prognostic factor for overall survival. Our findings suggest that a high serum hepcidin-25 level may indicate the progression of RCC, and that upregulation of hepcidin mRNA expression in tumor tissue may be related to increased metastatic potential

  4. Surgical management of renal cell carcinoma with inferior vena caval thrombus: A teaching hospital experience

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    Kulkarni Jagdeesh

    2007-01-01

    Full Text Available Purpose: To evaluate the outcome of patients of renal cell carcinoma (RCC with inferior vena caval (IVC thrombus treated by radical nephrectomy and IVC thrombectomy in terms of clinical and pathological factors and prognosis. Materials and Methods: Sixty-three consecutive patients of RCC with IVC thrombus who underwent radical nephrectomy with IVC thrombectomy between June 1993 and May 2003 were included in this retrospective analysis. Data was analyzed in terms of clinical factors, such as level of thrombus, and pathological factors, such as grade, local invasion and N status. Results: Tumor thrombus level was infrahepatic in 35 patients, retrohepatic in 20 and suprahepatic in 8, including 5 with right atrial thrombus. The immediate post-operative mortality was 3%, and the incidence of major post-operative complications was 34%, but most of them improved after conservative management except one who needed surgery for burst abdomen. The disease free survival (DFS was 48.5%, 50.6%, 66.6% and 40% for infrahepatic, retrohepatic, suprahepatic and intra-atrial tumors, respectively. Of the histological types, patients with clear cell tumors had the best prognosis; those with granular cell had the worst prognosis (DFS of 53.5% vs 33.3%, though statistically not significant. Grade-2 tumors had better prognosis than grade-4 tumors (DFS 66.6% vs 0%, P < 0.001. Sixty-eight percent of patients without perinephric fat invasion were free of disease as compared to 31% of those with perinephric fat invasion (P < 0.01. Further, N status showed DFS of 60.9% in patients with negative nodes and 30% in patients with positive nodes (P < 0.05. Conclusion: Though surgery for RCC with IVC thrombus has high morbidity, it can give good results in terms of prolonged DFS in expert hands. Regarding long-term survival, pathological factors, such as local stage and grade, are more important than clinical factors, such as level of thrombus.

  5. Factors associated with improved survival following surgery for renal cell carcinoma spinal metastases.

    Science.gov (United States)

    Petteys, Rory J; Spitz, Steven M; Goodwin, C Rory; Abu-Bonsrah, Nancy; Bydon, Ali; Witham, Timothy F; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Sciubba, Daniel M

    2016-08-01

    OBJECTIVE Renal cell carcinoma (RCC) frequently metastasizes to the spine, causing pain or neurological dysfunction, and is often resistant to standard therapies. Spinal surgery is frequently required, but may result in high morbidity rates. The authors sought to identify prognostic factors and determine clinical outcomes in patients undergoing surgery for RCC spinal metastases. METHODS The authors searched the records of patients who had undergone spinal surgery for metastatic disease at a single institution during a 12-year period and retrieved data for 30 patients with metastatic RCC. The records were retrospectively reviewed for data on preoperative conditions, treatment, and survival. Statistical analyses (i.e., Kaplan-Meier survival analysis and log-rank test in univariate analysis) were performed with R version 2.15.2. RESULTS The 30 patients (23 men and 7 women with a mean age of 57.6 years [range 29-79 years]) had in total 40 spinal surgeries for metastatic RCC. The indications for surgery included pain (70%) and weakness (30%). Fourteen patients (47%) had a Spinal Instability Neoplastic Score (SINS) indicating indeterminate or impending instability, and 6 patients (20%) had a SINS denoting instability. The median length of postoperative survival estimated with Kaplan-Meier analysis was 11.4 months. Younger age (p = 0.001) and disease control at the primary site (p = 0.005), were both significantly associated with improved survival. In contrast, visceral (p = 0.002) and osseous (p = 0.009) metastases, nonambulatory status (p = 0.001), and major comorbidities (p = 0.015) were all significantly associated with decreased survival. Postoperative Frankel grades were the same or had improved in 78% of patients. Major complications occurred in 9 patients, and there were 3 deaths (10%) during the 30-day in-hospital period. Three en bloc resections were performed. CONCLUSIONS Resection and fixation may provide pain relief and neurological stabilization in patients

  6. Renal cell carcinoma and synchronous thyroid metastasis with neoplastic thrombosis of the internal jugular vein: report of a case.

    Science.gov (United States)

    Matei, Deliu-Victor; Brescia, Antonio; Nordio, Andrea; Spinelli, Matteo Giulio; Melegari, Sara; Cozzi, Gabriele; Andrioli, Massimiliano; Salvatori, Pietro

    2011-12-01

    A case of thyroid metastasis of a renal clear cell carcinoma is presented. The fine-needle aspiration cytology pointed out the primary tumor origin. The patient underwent robot-assisted radical nephrectomy and contextual thyroidectomy. During the operative procedure, a neoplastic thrombus extending from the thyroid metastasis and protruding into the internal jugular vein was found. As a result, thrombectomy and ligation of the internal jugular vein were required. In cases of single synchronous thyroid metastases form RCC, radical surgery should be advisable. Robotic approach allows to associate major surgery procedures, as nephrectomy, with radical metastasectomy.

  7. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    OpenAIRE

    Steven M Yip; Heng, Daniel Y. C.; Tang, Patricia A.

    2016-01-01

    Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium dat...

  8. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma

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    Mahesh Deshmukh

    2011-01-01

    Full Text Available Tubulocystic renal cell carcinoma (TCRCC is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

  9. The high-dose aldesleukin (IL-2) "select" trial: a trial designed to prospectively validate predictive models of response to high-dose IL-2 treatment in patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Clement, Jessica M; McDermott, David F

    2009-08-01

    For patients with metastatic renal cell carcinoma (RCC), the prognosis is poor. Despite the recent approval of drugs such as sorafenib, sunitinib, and temsirolimus, durable remissions of metastatic disease are rare. This is largely due to the fact that these drugs, while effective, do not result in the eradication of disease. In 1992, the FDA approved the use of high-dose interleukin-2 (IL-2) for the treatment of patients with metastatic RCC because of a small number of patients that achieved durable responses. However, IL-2 has not become a mainstay of treatment because of the expense and toxicity associated with this therapy. This review article discusses a phase II trial that investigates predictive biomarkers that might help clinicians identify the patient population with metastatic RCC that would benefit from IL-2 therapy and therefore limit patients who receive this toxic therapy to those most likely to benefit. PMID:19692326

  10. TFE3 Translocation-Associated Renal Cell Carcinoma Presenting as Avascular Necrosis of the Femur in a 19-Year-Old Patient: Case Report and Review of the Literature

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    T. Nelius

    2011-01-01

    Full Text Available In the United States, renal cell carcinoma (RCC accounts for approximately 3% of adult malignancies and 90–95% of all neoplasms arising from the kidney. According to the National Cancer Institute, 58 240 new cases and 13 040 deaths from renal cancer will occur in 2010. RCC usually occurs in older adults between the ages of 50 and 70 and is rare in young adults and children. We describe a case of a TFE3 translocation-associated RCC in a 19-year-old patient presenting as avascular necrosis of the femur. Due to the rarity of this malignancy, we present this case including a review of the existing literature relative to diagnosis and treatment.

  11. Cisplatin, Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2016-05-16

    Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  12. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    OpenAIRE

    Yeliz Bilir; Erkan Gokce; Banu Ozturk; Faik Alev Deresoy; Ruken Yuksekkaya; Emel Yaman

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity...

  13. p21-activated kinase 1 determines stem-like phenotype and sunitinib resistance via NF-κB/IL-6 activation in renal cell carcinoma.

    Science.gov (United States)

    Zhu, Y; Liu, H; Xu, L; An, H; Liu, W; Liu, Y; Lin, Z; Xu, J

    2015-02-12

    The p21-activated kinase 1 (PAK1), a serine/threonine kinase that orchestrates cytoskeletal remodeling and cell motility, has been shown to function as downstream node for various oncogenic signaling pathways to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, resulting in tumor formation and invasiveness. Although alterations in PAK1 expression and activity have been detected in various human malignancies, its potential biological and clinical significance in renal cell carcinoma (RCC) remains obscure. In this study, we found increased PAK1 and phosphorylated PAK1 levels in tumor tissues according to TNM stage progression. Elevated phosphorylated PAK1 levels associated with progressive features and indicated unfavorable overall survival (OS) as an independent adverse prognosticator for patients with RCC. Moreover, PAK1 kinase activation with constitutive active PAK1 mutant T423E promoted growth, colony formation, migration, invasion and stem-like phenotype of RCC cells, and vice versa, in PAK1 inhibition by PAK1 kinase inactivation with specific PAK1 shRNA, dead kinase PAK1 mutant K299R or allosteric inhibitor IPA3. Stem-like phenotype due to sunitinib administration via increased PAK1 kinase activation could be ameliorated by PAK1 shRNA, PAK1 mutant K299R and IPA3. Furthermore, nuclear factor-κB (NF-κB)/interleukin-6 (IL-6) activation was found to be responsible for PAK1-mediated stem-like phenotype following sunitinib treatment. Both IL-6 neutralizing antibody and IPA3 administration enhanced tumor growth inhibition effect of sunitinib treatment on RCC cells in vitro and in vivo. Our results unraveled that oncogenic activation of PAK1 defines an important mechanism for maintaining stem-like phenotype and sunitinib resistance through NF-κB/IL-6 activation in RCC, lending PAK1-mediated NF-κB/IL-6 activation considerable appeal as novel pharmacological therapeutic targets against sunitinib resistance.

  14. Prognostic factors of the therapeutic efficacy of mTOR and VEGFR inhibitors in patients with metastatic renal cell carcinoma

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    Е. А. Voroshilova

    2015-01-01

    Full Text Available Background. Thorough study of the molecular genetic alterations in patients with hereditary and sporadic renal cell carcinoma (RCC enabled to reveal potential therapeutic targets - vascular endothelial growth factor (VEGF, platelet-derived growth factor (PDGF, growth factor receptors (VEGFR, PDGFR, EGFR, FGFR, mTOR signaling protein. Advances in targeted therapy treatment in the current therapeutic practice have brought a problem of its rational use and ultimately effective outcomes. The main solution of solving this problem is to establish independent clinical and laboratory prognostic factors and molecular markers which could predict the efficacy of targeted therapy.Objective – optimization of targeted therapy in patients with RCC by using both molecular and genetic prognostic factors as predictors of the treatment efficacy.Materials and methods. We assessed the level of mRNA expression of 13 potential target genes in primary tumor and metastatic site of patients suffering from metastatic RCC (n = 43 and evaluated the influence of the selected genes’ expression on the therapeutic efficacy of mTOR inhibitors and VEGFR inhibitors.Conclusion. VEGFR1 mRNA overexpression in metastatic site as well as mTOR and/or PI3K mRNA overexpression could be assessed as potential biomarkers in predicting the treatment efficacy of VEGFR inhibitors and mTOR inhibitors respectively. The higher expression of RAF1 mRNA and mTOR signaling pathway are not typical molecular alterations in patients with mRCC. RAF1 mRNA overexpression in metastatic site as well as activation of the alternative signaling pathway (RAS-RAF-MAPK in tumor cell are negative prognostic factors of the efficacy of targeted therapy. Activation of the signaling RAS-RAF-MAPK pathway in tumor cells is probably an alternative independent mechanism that “drives” tumor development in certain groups of patients.

  15. Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Vascular Changes Induced by Sunitinib in Papillary Renal Cell Carcinoma Xenograft Tumors

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    Gilda G. Hillman

    2009-09-01

    Full Text Available To investigate further the antiangiogenic potential of sunitinib for renal cell carcinoma (RCC treatment, its effects on tumor vasculature were monitored by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI using an orthotopic KCI-18 model of human RCC xenografts in nude mice. Tumor-bearing mice were treated with various doses of sunitinib, and vascular changes were assessed by DCE-MRI and histologic studies. Sunitinib induced dose-dependent vascular changes, which were observed both in kidney tumors and in normal kidneys by DCE-MRI. A dosage of 10 mg/kg per day caused mild changes in Gd uptake and clearance kinetics in kidney tumors. A dosage of 40 mg/kg per day induced increased vascular tumor permeability with Gd retention, probably resulting from the destruction of tumor vasculature, and also caused vascular alterations of normal vessels. However, sunitinib at 20 mg/kg per day caused increased tumor perfusion and decreased vascular permeability associated with thinning and regularization of tumor vessels while mildly affecting normal vessels as confirmed by histologic diagnosis. Alterations in tumor vasculature resulted in a significant inhibition of KCI-18 RCC tumor growth at sunitinib dosages of 20 and 40 mg/kg per day. Sunitinib also exerted a direct cytotoxic effect in KCI-18 cells in vitro. KCI-18 cells and tumors expressed vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β molecular targets of sunitinib that were modulated by the drug treatment. These data suggest that a sunitinib dosage of 20 mg/kg per day, which inhibits RCC tumor growth and regularizes tumor vessels with milder effects on normal vessels, could be used to improve blood flow for combination with chemotherapy. These studies emphasize the clinical potential of DCE-MRI in selecting the dose and schedule of antiangiogenic compounds.

  16. Clinical efficacy of sunitinib combined with autologous DC and CIK for patients with metastatic renal cell carcinoma

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    Liang ZHANG

    2014-01-01

    Full Text Available Objective To analyze the clinical efficacy and safety of sunitinib combined with autologous dentritic cell (DC and cytokine induced killer cell (CIK for patients suffering from metastatic renal cell carcinoma (mRCC. Methods Clinical data of 27 mRCC patients treated with sunitinib combined with autologous DC and CIK were reviewed retrospectively. Efficacy, quality of life, immunology and safety of this treatment were evaluated. Results Follow-up time ranged from 4 to 25 months. Out of all the patients, sunitinib was reduced in 1 and discontinued in 2 due to side effects; 1 patient quit for personal reasons; 14 patients developed progressive disease. The progression-free survival (PFS was 4 to 19.5 months. Ten patients died from tumor, the overall survival time (OS was 6 to 21 months. The median PFS was 16 months (95%CI 12.5-19.5. The OS was not achieved. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST. All the patients received treatment over 1 cycle. After one course of treatment, among 27 patients, 0 had complete remission (CR, 4 had partial remission (PR, 17 had stable disease (SD, and 6 had progressive disease (PD. The overall objective remission rate (ORR and disease control rate (DCR were 14.8% (4/27 and 77.8% (21/27, respectively. Sunitinib and autologous transfusion of DC and CIK improved the immune function and quality of life. The major adverse events were fatigue, hand-foot syndrome, hypertension, hypothyroidism, thrombocytopenia, neutropenia and fever. Most of the adverse events were ameliorated by supportive treatment or dose reduction. Conclusions  Sunitinib combined with autologous DC and CIK may be beneficial in the treatment of mRCC with acceptable toxic reactions, and it may be considered as a new approach for the comprehensive treatment of RCC. DOI: 10.11855/j.issn.0577-7402.2013.12.06

  17. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;

    2014-01-01

    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  18. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  19. CLINICAL VALUE OF THE MARKERS OF PROLIFERATION AND APOPTOSIS IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-07-01

    Full Text Available Renal cell carcinoma (RCC is a heterogeneous disease in which the patients survive for months to years. At the present time the prognostic models have no sufficient information or exact prognostic value. Cell proliferation and apoptosis play a key role in cell cycle regulation; and impairment in these processes is commonly detected in different human tumors. The investigation enrolled 76 patients (49 men, 27 women aged 32 to 73 years (mean age 56 ± 7.6 years diagnosed with RCC. The follow-up was 8 to 116 months (mean 36.5 months. All the patients underwent nephrectomy; antibodies against р53, Bcl-2, and Ki-67 were investigated by immunohistochemistry. The expression of p53 and none or reduced expression of Bcl-2 are poor prognostic factors and associated with the metastatic potential of a tumor and with low relapse-free survival. High Ki-67 levels are a risk factor for metastases. A combination of p53 expression and high proliferative activity reflects the aggressive potential of a tumor and suggests the high risk of metastases just at the disease diagnosis and early tumor dissemination. 

  20. Basal cell carcinoma in oculo-cutaneous albinism

    OpenAIRE

    Ajay Kumar; Ashish Chauhan; Subhash Kashyap

    2016-01-01

    The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition ...

  1. Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    This study was conducted to clarify the genomic profiles of metastatic clear cell renal cell carcinomas (ccRCCs) and identify the genes responsible for development of metastasis. We analyzed the genomic profiles of 20 cases of primary ccRCC and their corresponding metastases using array-based comparative genomic hybridization, and identified 32 chromosomal regions in which gene copy number alterations were detected more frequently in metastases than in the primary tumors. Among these 32 regions, 9p24.1-p13.3 loss was the most statistically significant alteration. Furthermore, we found that patients with 9p24.1-p13.3 loss in primary tumors exhibited significantly lower rates of recurrence-free and cancer-specific survival, suggesting that 9p loss in the primary tumor is a potential biomarker predicting early recurrence of metastasis. Interestingly, the genomic profiles of primary tumors with 9p loss resembled those of their corresponding metastases, though 9p loss was accumulated in the metastases derived from the primary tumors without 9p loss. Comparison of the mRNA expression levels revealed that 2 of 58 genes located at 9p24.1-p13.3 were downregulated due to gene copy number loss in ccRCCs. An overexpression study of these two genes in ccRCC cell lines revealed that downregulation of NDUFB6 due to loss at 9p24.1-p13.3 may confer a growth advantage on metastatic ccRCC cells. These results were confirmed by analyzing the data of 405 cases of ccRCC obtained from The Cancer Genome Atlas (TCGA). On the basis of our present data, we propose that NDUFB6 is a possible tumor suppressor of metastatic ccRCCs

  2. The changes of lipid metabolism in advanced renal cell carcinoma patients treated with everolimus: a new pharmacodynamic marker?

    Directory of Open Access Journals (Sweden)

    Francesco Pantano

    Full Text Available Everolimus is a mammalian target of rapamycin (mTOR inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC. We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C, triglycerides (T, body mass index (BMI, fasting blood glucose level (FBG and blood pressure (BP levels and the outcome of patients treated with everolimus for mRCC.177 patients were included in this retrospective analysis. Time to progression (TTP, clinical benefit (CB and overall survival (OS were evaluated.Basal BMI was significantly higher in patients who experienced a CB (p=0,0145. C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001. Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030, C (8 vs 5, p=0.042 and C+T raise (10.9 vs 5.0, p=0.003. At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005. T raise (21.0 vs 14.0, p=0.002 and C+T increase (21.0 vs 14.0, p=0.006 were correlated with improved OS but were not significant at multivariate analysis.C+T raise is an early predictor for everolimus efficacy for patients with mRCC.

  3. What role do combinations of interferon and targeted agents play in the first-line therapy of metastatic renal cell carcinoma?

    Science.gov (United States)

    Bukowski, Ronald M

    2008-12-01

    Interferons (IFNs) are a class of cytokines with pleotropic actions that regulate a variety of cellular activities. Clinical trials with recombinant IFNs (IFN-alpha2a and IFN-alpha2b) have demonstrated clinical activity in patients with advanced renal cell carcinoma (RCC). Their efficacy is characterized by a low overall tumor regression rate of < 15%, progression-free survival of 4-5 months, and overall median survival of 10-18 months. This cytokine became the standard of care for patients with metastatic RCC and was then used as the comparator arm in a series of phase II and III clinical trials that have defined a new treatment paradigm for patients with advanced RCC. This paradigm uses the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib, the mammalian target of rapamycin (mTOR) inhibitor temsirolimus, and the vascular endothelial growth factor monoclonal antibody bevacizumab. These 3 categories of agents were then investigated in combination with IFN-alpha in a series of preclinical and clinical studies. The collective data from these reports suggest the combination of IFN-alpha and bevacizumab is active and has a role in RCC therapy, whereas combinations with the TKIs or mTOR inhibitors have limited efficacy and/or excessive toxicity. The clinical and preclinical studies leading to these conclusions are reviewed herein.

  4. Immunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma.

    Science.gov (United States)

    Demirović, Alma; Džombeta, Tihana; Tomas, Davor; Spajić, Borislav; Pavić, Ivana; Hudolin, Tvrtko; Milošević, Milan; Cupić, Hrvoje; Krušlin, Božo

    2010-10-15

    The distinction between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), especially the eosinophilic variant, can often be difficult. Our study has documented for the first time the expression of MAGE-A3/4 and NY-ESO-1 cancer testis antigens (CTAs) in these tumors. A total of 35 patients (17 ROs and 18 ChRCCs) were included in the study. Two antibodies were used for immunohistochemical staining: 57B recognizing multiple MAGE-A and D8.38 recognizing NY-ESO-1 CTAs. Fifteen (88.2%) samples of RO stained positively for both MAGE-A3/4 and NY-ESO-1 antigens. Regarding ChRCC, seven (38.9%) stained positively for MAGE-A3/4 and six (33.3%) for NY-ESO-1 antigens. Median MAGE-A3/4 expression was moderately positive in RO and negative in ChRCC. The difference in MAGE-A3/4 expression between two tumor groups was significant (P=0.0013). Median NY-ESO-1 expression was strongly positive in RO and negative in ChRCC. The difference in NY-ESO-1 expression between two tumor groups was also significant (P=0.0008). Our study has shown that RO had a significantly higher expression of both CTAs. However, additional research is needed to clarify their potential diagnostic implications.

  5. Paraneoplastic Cough and Renal Cell Carcinoma.

    Science.gov (United States)

    Sullivan, Stephen

    2016-01-01

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

  6. Sunitinib benefits patients with renal cell carcinoma

    Science.gov (United States)

    Findings from clinical trial patients with metastatic renal cell carcinoma, a common kidney cancer, show they did not have accelerated tumor growth after treatment with sunitinib, in contrast to some study results in animals.

  7. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    Science.gov (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  8. Squamous cell carcinoma arising in an odontogenic cyst

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jae Jung; Hwang, Eui Hwan; Lee, Sang Rae [Kyunghee University College of Medicine, Seoul (Korea, Republic of); Choi, Jeong Hee [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)

    2003-12-15

    Squamous cell carcinoma arising in an odontogenic cyst is uncommon. The diagnosis of carcinoma arising in a cyst requires that there must be an area of microscopic transition from the benign epithelial cyst lining to the invasive squamous cell carcinoma. We report a histopathologically proven case of squamous cell carcinoma arising in a residual mandibular cyst in a 54-year-old woman.

  9. Hurthle cell carcinoma of the thyroid

    OpenAIRE

    Sandoval, Mark Anthony S; Paz-Pacheco, Elizabeth

    2011-01-01

    A 63-year-old man consulted for a non-toxic thyroid nodule of 2 years’ duration. Fine needle aspiration revealed cell findings consistent with papillary thyroid carcinoma. He eventually underwent total thyroidectomy. Microscopic examination revealed histologic features of Hurthle cell carcinoma of the thyroid. He received radioactive iodine therapy and suppressive levothyroxine treatment. Post-therapy whole body iodine-131 scan revealed thyroid tissue remnants limited to the anterior neck. Fo...

  10. Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

    Science.gov (United States)

    Alfaro, Clint M; Jarmusch, Alan K; Pirro, Valentina; Kerian, Kevin S; Masterson, Timothy A; Cheng, Liang; Cooks, R Graham

    2016-08-01

    Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1-5 cm(3)), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700-1000) data provided the separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA-compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98 and 95 %, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization-MS imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700-1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100 and 89 %, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1 + Cl](-) and 844 [PC 38:4 + Cl](-) for TS vs. m/z 788 [PS 36:1 - H](-) and 810 [PS 38:4 - H](-) for DESI), while m/z 885 ([PI 38:4 - H](-)) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis are discussed. Graphical abstract Touch spray-mass spectrometry used for

  11. Efficacy and safety of axitinib in elderly patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Miyake, Hideaki; Harada, Ken-Ichi; Ozono, Seiichiro; Fujisawa, Masato

    2016-08-01

    The objective of this study was to analyze the impact of age on clinical outcomes of metastatic renal cell carcinoma (mRCC) patients receiving axitinib. This study included 144 consecutive mRCC patients who received axitinib for at least 12 weeks as second-line therapy in a routine clinical setting. The efficacy, safety and quality of life (QOL) were compared between patients aged <75 (n = 116) and ≥75 (n = 28) years. No significant differences in the clinicopathological characteristics were noted between younger and older patients. There was no significant difference in the response rate, clinical benefit rate or proportion of patients going on to receive third-line therapy between these two groups. In addition, the progression-free and overall survivals in older patients were similar to those in younger patients. There were no significant differences in the incidences of adverse events between these two groups, except for that of fatigue, which was significantly more frequent in older than younger patients. There was no significant difference in the incidence of the discontinuation of axitinib due to adverse events between the two groups. QOL assessment at 12 weeks after the introduction of axitinib using the Medical Outcomes Study 36-Item Short Form showed no significant differences in any of the eight scale scores between the two groups. Taken together, it might be possible to achieve clinical outcomes in older patients receiving axitinib comparable to those in younger patients, suggesting that advanced age should not be a contraindication to treatment with axitinib as a second-line setting in mRCC patients. PMID:27444960

  12. Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy

    Directory of Open Access Journals (Sweden)

    Brian W. Cross

    2012-01-01

    Full Text Available Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR and overall survival in localized renal cell carcinoma (RCC following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr, intermediate (20.1–50.0 mm/hr, and high risk (>50.0 mm/hr groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI survival was 44.1 (42.6–45.5 months, 35.5 (32.3–38.8 months, and 32.1 (25.5–38.6 months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649 and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228 increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC.

  13. The antioxidant protein PARK7 plays an important role in cell resistance to Cisplatin-induced apoptosis in case of clear cell renal cell carcinoma.

    Science.gov (United States)

    Trivedi, Rachana; Dihazi, Gry H; Eltoweissy, Marwa; Mishra, Durga P; Mueller, Gerhard A; Dihazi, Hassan

    2016-08-01

    Clear cell renal cell carcinoma (ccRCC) is the most malignant tumor in the adult kidney. Many factors are responsible for the development and progression of this tumor. Increased reactive oxygen species accumulation and altered redox status have been observed in cancer cells and this biochemical property of cancer cells can be exploited for therapeutic benefits. In earlier work we identified and characterize Protein DJ-1 (PARK7) as an oxidative stress squevenger in renal cells exposed to oxidative stress. To investigate whether the PARK7 or other oxidative stress proteins play a role in the renal cell carcinoma and its sensitivity or resistance to cytostatic drug treatment, differential proteomics analysis was performed with a cell model for clear cell renal carcinoma (Caki-2 and A498). Caki-2 cells were treated with cisplatin and differentially expressed proteins were investigated. The cisplatin treatment resulted in an increase in reactive oxygen species accumulation and ultimately apoptosis of Caki-2 and A498 cells. In parallel, the apoptotic effect was accompanied by a significant downregulation of antioxidant proteins especially PARK7. Knockdown of PARK7 using siRNA and overexpression using plasmid highlights the role of PARK7 as a key player in renal cell carcinoma response to cisplatin induced apoptosis. Overexpression of PARK7 resulted in significant decrease in apoptosis, whereas knockdown of the protein was accompanied by an increase in apoptosis in Caki-2 and A498 cells treated with cisplatin. These results highlights for the first time the important role of PARK7 in cisplatin induced apoptosis in clear renal cell carcinoma cells. PMID:27112662

  14. Prognostic investigations of B7-H1 and B7-H4 expression levels as independent predictor markers of renal cell carcinoma.

    Science.gov (United States)

    Safaei, Hamid Reza; Rostamzadeh, Ayoob; Rahmani, Omid; Mohammadi, Mohsen; Ghaderi, Omar; Yahaghi, Hamid; Ahmadi, Koroosh

    2016-06-01

    In order to evaluate the correlation of B7-H4 and B7-H1 with renal cell carcinoma (RCC), we analyzed B7-H1 and B7-H4 expressions and their clinical significance by immunohistochemical method. Our result indicated that B7-H4-positive staining was detected in 58.13 % of RCC tissues (25 tissues tumors), and there were 18 tissues of patients without detectable B7-H4. Furthermore, 21 cases (48.83 %) were B7-H1-positive. Positive tumor expressions of B7-H4 and B7-H1 were markedly related to advanced TNM stage (P = 0.001; P = 0.014), high grade (P = 0.001; P = 002), and larger tumor size (P = 0.002; P = 024) in RCC tissues than patients with B7-H4-negative and B7-H1-negative in RCC tissues. The patients with B7-H1 and B7-H4-positive expressions were found to be markedly correlated with the overall survival of the patients (P < 0.05) and tended to have an increased risk of death when compared with negative expression groups. Univariate analysis showed that B7-H4 and B7-H1 expressions, TNM stage, high grade, and tumor size were significantly related to the prognosis of RCC. Furthermore, multivariate analysis showed that B7-H4 and B7-H1 expressions decreased overall survival. The adjusted HR for B7-H1 was 2.83 (95 % CI 1.210-2.971; P = 0.031) and also was 2.918 (95 % CI 1.243-3.102; P = 0.006) for B7-H4 that showed these markers were independent prognostic factors in RCC patients. The expressions of B7-H1 and B7-H4 in RCC patients indicate that these markers may be as a predictor of tumor development and death risk. Further investigations can be helpful to confirm B7-H1 and B7-H4 roles as an independent predictor of clinical RCC outcome. PMID:26687644

  15. Renal Cell Carcinoma Metastasized to Pagetic Bone.

    Science.gov (United States)

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

    2016-01-01

    Paget's disease of the bone, historically known as osteitis deformans, is an uncommon disease typically affecting individuals of European descent. Patients with Paget's disease of the bone are at increased risk for primary bone neoplasms, particularly osteosarcoma. Many cases of metastatic disease to pagetic bone have been reported. However, renal cell carcinoma metastasized to pagetic bone is extremely rare. A 94-year-old male presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen demonstrated a large mass in the right kidney compatible with renal cell carcinoma. The patient was also noted to have Paget's disease of the pelvic bones and sacrum. Within the pagetic bone of the sacrum, there was an enhancing mass compatible with renal cell carcinoma. A subsequent biopsy of the renal lesion confirmed renal cell carcinoma. Paget's disease of the bone places the patient at an increased risk for bone neoplasms. The most commonly reported sites for malignant transformation are the femur, pelvis, and humerus. In cases of malignant transformation, osteosarcoma is the most common diagnosis. Breast, lung, and prostate carcinomas are the most common to metastasize to pagetic bone. Renal cell carcinoma associated with Paget's disease of the bone is very rare, with only one prior reported case. Malignancy in Paget's disease of the bone is uncommon with metastatic disease to pagetic bone being extremely rare. We report a patient diagnosed with concomitant renal cell carcinoma and metastatic disease within Paget's disease of the sacrum. Further research is needed to assess the true incidence of renal cell carcinoma associated with pagetic bone.

  16. DNA methyltransferase inhibitor-mediated apoptosis in the Wnt/β-catenin signal pathway in a renal cell carcinoma cell line.

    Science.gov (United States)

    Konac, Ece; Varol, Nuray; Yilmaz, Akin; Menevse, Sevda; Sozen, Sinan

    2013-09-01

    The Wnt signaling pathway is activated in most cancer types when Wnt antagonist genes are inactivated. Glycogen synthase kinase 3 (GSK3β) is an important regulator of the Wnt/β-catenin signaling pathway. The mechanisms underlying GSK3β regulation of neoplastic transformation and tumor development are unclear. Studies have raised the possibility that the Wnt signaling pathway may be implicated in renal cell carcinoma (RCC). Therefore, in the present study, we hypothesize that the expression and methylation status of the secreted frizzled-related protein 2 (sFRP2) gene, one of the secreted antagonists that bind Wnt protein, and re-expression of this gene with the demethylation agent (5-aza-2'-deoxycytidine; DAC) may induce apoptosis in RCC cells. To test this hypothesis, we investigated the relationship among epigenetic inactivation of sFRP2 and p-GSK3β (Ser9) and other Wnt antagonists (sFRP1, DKK3, WIF-1) and apoptotic factors (Bax and Caspase3) as well as the anti-apoptotic factor BCL2. Our results indicate that DAC-mediated inhibition of DNA methylation led to a re-activation of sFRP2 expression and increased expression levels of the Wnt antagonists and apoptotic factors. In contrast, the level of β-catenin (CTNNB1) expression decreased. The p-GSK3β (Ser9) protein level in Caki-2 cells was significantly down-regulated, while the DNA fragmentation rate increased after treatment with 5 μM DAC at 96 h. Our data show that sFRP2 functions as a tumor suppressor gene in RCC and that its restoration may offer a new therapeutic approach for the treatment of RCC. Moreover, our study draws attention to the regulatory features of epigenetic molecules and analyses their underlying molecular mechanisms of action and their potential use in clinical practice. PMID:23975733

  17. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Reiko; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori; Tanabe, Kazunari [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan)

    2016-06-15

    We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. (orig.)

  18. Mucinous tubular and spindle cell carcinoma of the kidney: Diagnosis by fine needle aspiration and review of the literature

    Directory of Open Access Journals (Sweden)

    Jiang Huimiao

    2015-01-01

    Full Text Available Renal mucinous tubular and spindle cell carcinoma (MTSCC was recently described as a distinct subtype of renal cell carcinoma (RCC in the 2004 World Health Organization classification of kidney tumors. MTSCC is a rare low grade malignancy with < 100 cases reported in the literature. To the best of our knowledge, there are 5 case reports with a total of 6 patients describing its diagnosis by fine needle aspiration (FNA. All of these cases were diagnosed as conventional RCC on FNA. Subsequent excisions proved them to be MTSCC. We herein report a case in a 67-year-old male. He presented with abdominal pain and was found to have a new colon adenocarcinoma with metastasis to the liver and lungs. The extent of disease made the patient ineligible for surgical excision, and he received chemotherapy. Work-up also revealed a kidney mass which was later biopsied by FNA and core biopsy. The tumor was composed of epithelial and spindled cell components embedded in a myxoid background. It was positive for CK7, AMCAR, vimentin, and epithelial membrane antigen. The tumor was diagnosed as MTSCC. One year later the kidney mass remained stable. However, the patient developed new metastasis to the liver from colonic primary. The kidney mass was not resected. Although rarely encountered in FNA cytology of the kidney, we believe the cytologic features of this tumor are distinctive and are different from conventional and other subtypes of RCC. Therefore, its accurate diagnosis on FNA is possible once pathologists are aware that MTSCC should be considered in the differential diagnosis of kidney tumors.

  19. Renal cell carcinomas with t(6;11)(p21;q12) presenting with tubulocystic renal cell carcinoma-like features.

    Science.gov (United States)

    Rao, Qiu; Zhang, Xiu-Mei; Tu, Pin; Xia, Qiu-Yuan; Shen, Qin; Zhou, Xiao-Jun; Shi, Qun-Li

    2013-01-01

    In this study, we reported an additional genetically confirmed case of renal cell carcinomas (RCCs) with t(6;11)(p21;q12) showing an unusual histological pattern. Histologically, the tumor was entirely composed of small to intermediate sized tubules and cysts. The tubules and cysts were lined by a single layer of flat, hobnail, cuboidal to columnar epithelial cells. Most cells demonstrated abundant eosinophilic cytoplasm with regular, round or oval nuclei and some inconspicuous nucleoli. All these morphological features are suggestive of tubulocystic carcinoma of the kidney. However, the tumor demonstrated moderately (2+) or strongly (3+) positive staining for TFEB, Cathepsin K, Ksp-cadherin, and vimentin but negative for TFE3, CD10, HMB45, melan A, CKpan, and CK7. Using a recently developed TFEB split FISH assay, the presence of TFEB rearrangement was demonstrated. Our results support the clinical application of a TFEB break-apart FISH assay for diagnosis and confirmation of TFEB RCC and further expand the morphologic spectrum that may be present in these neoplasms, sometimes raising a challenging differential diagnosis with other renal tumors.

  20. Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma

    Science.gov (United States)

    Gore, M E; Szczylik, C; Porta, C; Bracarda, S; Bjarnason, G A; Oudard, S; Lee, S-H; Haanen, J; Castellano, D; Vrdoljak, E; Schöffski, P; Mainwaring, P; Hawkins, R E; Crinò, L; Kim, T M; Carteni, G; Eberhardt, W E E; Zhang, K; Fly, K; Matczak, E; Lechuga, M J; Hariharan, S; Bukowski, R

    2015-01-01

    Background: We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials. Methods: Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on–2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice. Results: A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15–17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8–10.0) and 18.7 months (95% CI: 17.5–19.5). Median PFS in subgroups of interest: aged ⩾65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ⩾2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand–foot syndrome (each 7%). Conclusion: Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results. PMID:26086878

  1. Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

    Science.gov (United States)

    Gołąbek, T; Przydacz, M; Okoń, K; Kopczyński, J; Bukowczan, J; Sobczyński, R; Curyło, Ł; Gołąbek, K; Curyło, Ł; Chłosta, P

    2016-06-01

    The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up.

  2. Development of coronary artery stenosis in a patient with metastatic renal cell carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Pantaleo Maria

    2012-06-01

    Full Text Available Abstract Background Tyrosine kinase inhibitors (TKIs are currently approved for the treatment of metastatic renal cell carcinoma (mRCC. The cardiotoxic effects of sorafenib and sunitinib may cause hypertension, left ventricular ejection fraction (LVEF dysfunction and/or congestive heart failure (CHF, and arterial thrombo-embolic events (ATE. Only three cases of coronary artery disease related to sorafenib therapy have been described in the literature, and all were due to arterial vasospasm without evidence of coronary artery stenosis on angiography. Cardiotoxicity is commonly associated with the presence of cardiovascular risk factors, such as a history of hypertension or coronary artery disease. Case presentation We describe a patient who experienced an unusual cardiac event after 2 years of sorafenib treatment. A 58-year-old man with mRCC developed acute coronary syndrome (ischemia/infarction associated with critical sub-occlusion of the common trunk of the left coronary artery and some of its branches, which was documented on coronary angiography. The patient underwent triple coronary artery bypass surgery, and sorafenib treatment was discontinued. He did not have any cardiovascular risk factors, and his cardiac function and morphology were normal prior to sorafenib treatment. Conclusions Further investigation of a larger patient population is needed to better understand cardiac damage due to TKI treatment. Understanding the usefulness of careful cardiovascular monitoring might be important for the prevention of fatal cardiovascular events, and to avoid discontinuation of therapy for the underlying cancer.

  3. Tumour thrombus consistency has no impact on survival in patients with renal cell carcinoma.

    Science.gov (United States)

    Gołąbek, T; Przydacz, M; Okoń, K; Kopczyński, J; Bukowczan, J; Sobczyński, R; Curyło, Ł; Gołąbek, K; Curyło, Ł; Chłosta, P

    2016-06-01

    The prognosis of renal cell carcinoma (RCC) with venous tumour thrombus (VTT) is variable and not always possible to predict. The prognostic impact and independence of tumour thrombus-related factors including the recently introduced tumour thrombus consistency (TTC) on overall survival remain controversial. The aim of this study was to investigate the prognostic role of TTC in patients' survival. We determined the tumour thrombus consistency (solid vs. friable) in a cohort of 84 patients with RCC and VTT who underwent nephrectomy with thrombectomy, and performed a retrospective evaluation of the patients' data from the prospectively maintained database. A total of 45% of patients had solid thrombus (sTT) and 55% had friable thrombus (fTT). The venous tumour thrombus consistency was not predictive of overall survival. Further studies, preferably prospective and with a larger number of patients, are needed to validate the obtained results, as well as to evaluate the usefulness of tumour thrombus consistency in clinical practice for stratifying the risk of recurrence and planning further follow-up. PMID:27543869

  4. Renal cell carcinoma: review of novel single-agent therapeutics and combination regimens.

    Science.gov (United States)

    Amato, R J

    2005-01-01

    A search of the Medline database and ASCO 2003 conference proceedings was conducted to identify clinical trials currently underway using single-agent therapy for renal cell carcinoma (RCC). Combination trials were identified using the ASCO 2003 conference proceedings. Fourteen single-agent therapies employing different mechanisms of action were identified in the published literature: imatinib mesylate (Gleevec); bevacizumab (Avastin); thalidomide (Thalomid); gefitinib (ZD1839) (Iressa); cetuximab (IMC-C225) (Erbitux); bortezomib (PS-341) (Velcade); HSPPC-96 (Oncophage); BAY 59-8862; ABT-510; G250; CCI-779; SU5416; PTK/ZK; and ABX-EGF. Six distinct fields of clinical research have emerged: monoclonal antibodies, small molecules, vaccines, second-generation taxanes, nonapeptides and immunomodulators. Five combination regimens, primarily biological response modifiers (interleukin-2 or interferon-alpha), chemotherapy- or thalidomide-based, were identified. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed based on each study's reported criteria: antitumor response (regression or stability) ranged from 5% to 71%. In the past several years, significant advances in the underlying biological mechanisms of RCC, particularly the role of tumor angiogenesis, have permitted the design of molecularly targeted therapeutics. Based on preliminary and limited studies, combination therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted.

  5. Drug therapy of renal cell carcinoma%肾癌的药物治疗

    Institute of Scientific and Technical Information of China (English)

    康马飞

    2008-01-01

    肾癌的药物治疗目前仍以免疫化学治疗为主,单纯化疗也有效,吉西他滨联合顺铂是目前的标准化疗方案.靶向治疗药物的出现使肾癌的治疗发生了改变,多靶点受体酪氨酸激酶抑制剂(如舒尼替尼和索拉非尼)、哺乳动物雷帕霉素靶蛋白抑制剂(temsirolimus)和抗肿瘤单克隆抗体(如贝伐单抗)等已成为肾癌的一线治疗选择.%Immunochemotherapy is still the primary drug therapy of renal cell carcinoma(RCC), and chemotherapy is effective too. The combination of gemcitabine and cisplatin is the standard regimen now. How-ever, emerge of targeted therapeutic agents has altered the treatment of RCC. Multitargeted tyrosine kinase in-hibitor, such as sunitinib and sorafenib, and mammalian target of rapamycin (roTOR) inhibitors( temsiroll-mus), and anti-tumor monoclonal antibody, such as bevacizumab, have already become the first line election.

  6. A prospective Phase II trial of using extracranial stereotactic radiotherapy in primary and metastatic renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Svedman, Christer; Sandstroem, Per; Pisa, Pavel; Kaelkner, Karl-Mikael; Nilsson, Sten; Wersaell, Peter [Karolinska Univ. Hospital, Radiumhemmet, Stockholm (Sweden). Dept. of General Oncology; Blomgren, Henric [Malzoni Radiosurgery Inst., Agropoli (Italy); Lax, Ingemar [Karolinska Univ. Hospital, Radiumhemmet, Stockholm (Sweden). Dept. of Radiotherapy

    2006-09-15

    A retrospective study has indicated that stereotactic radiotherapy (SRT) has a value in treating both primary tumors and singular metastatic lesions that cause local symptoms. Here we present the results of a prospective study evaluating the safety and local efficacy of SRT in metastatic or inoperable primary renal cancer. Thirty patients with metastatic renal cell carcinoma (RCC) or inoperable primary RCC received high-dose fraction SRT. In total, 82 lesions were treated. Dose/fractionation schedules varied depending on target location and size. The most frequently used fractionations were 8 Gyx4, 10 Gyx4, 15 Gyx2 or 15 Gyx3 prescribed to the periphery of the PTV. Local control, defined as radiologically stable disease (SD) or partial/complete response (PR/CR) was obtained in 98% of treated lesions but 19% of lesions were in patients with a follow time of less than 6 months. CR was observed in 21% of the patients and 58% of the patients had a partial volume reduction or local stable disease after a median follow-up of 52 months (range 11-66) for patients alive and 18 months (range 4-57) for deceased patients. Local progression was seen in two lesions. Side effects were grade I-II in 90% of cases. The overall survival was 32 months. SRT for patients with primary and metastatic RCC resulted in high local control rate with generally low toxicity. The method can thus be considered a therapeutic option to surgery in patients with a limited number of metastases, as local treatment in RCC with an indolent presentation or as a method of reducing tumor burden prior to medical treatment.

  7. Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma

    Science.gov (United States)

    He, Hai-Tao; Xu, Mu; Kuang, Ye; Han, Xiao-Yun; Wang, Ming-Qi; Yang, Qing

    2016-01-01

    Background Accumulating evidence suggests long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of cancers. However, their functions in chromophobe renal cell carcinoma (chRCC) are not fully understood. Methods We analyzed the expression profiles of lncRNA, microRNA, and protein-coding RNA, along with the clinical information of 59 primary chRCC patients collected from The Cancer Genome Atlas database to identify lncRNA biomarkers for prognosis. We also constructed an lncRNA–microRNA–mRNA coexpression network (competitive endogenous RNAs network) by bioinformational approach. Results One hundred and forty-two lncRNAs were found to be differentially expressed between the cancer and normal tissues (fold change ≥1.5, P<0.001). Among them, 12 lncRNAs were also differentially expressed with the corresponding clinical characteristics (fold change ≥1.5, P<0.01). Besides, 7 lncRNAs (COL18A1-AS, BRE-AS1, SNHG7, TMEM51-AS1, C21orf62-AS1, LINC00336, and LINC00882) were identified to be significantly correlated with overall survival (log-rank P<0.05). A competitive endogenous RNA network in chRCC containing 16 lncRNAs, 18 miRNAs, and 168 protein-coding RNAs was constructed. Conclusion Our results identified specific lncRNAs associated with chRCC progression and prognosis, and presented competing endogenous RNA potential of lncRNAs in the tumor.

  8. Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability

    NARCIS (Netherlands)

    den Bakker, Michael A.; Willemsen, Sten; Gruenberg, Katrien; Noorduijn, L. Arnold; van Oosterhout, Matthijs F. M.; van Suylen, Robert J.; Timens, Wim; Vrugt, Bart; Wiersma-van Tilburg, Anne; Thunnissen, Frederik B. J. M.

    2010-01-01

    Aims: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation. Methods and results: One hundred and seventy cases of SCLC,

  9. Open Partial Nephrectomy in Solitary Kidney with Multiple Renal Cell Carcinoma: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Ji-rui Niu; Quan-zong Mao; Zhi-gang Ji

    2011-01-01

    RENAL cell carcinoma (RCC) in a solitary kidney presents a unique clinical challenge to urological surgeons.Partial nephrectomy (PN) or nephron-sparing surgery in this condition provides good oncological and renal fuctional outcomes with an acceptable complication rate.1,2 Long-term renal function remains stable in most patients with solitary kidneys after a reduction of more than 50% in renal mass.3 PN is a surgical procedure reserved for patients with a tumor in a solitary kidney,bilateral renal tumors,or renal function impairment.4 The challenge of preserving renal parenchyma is significantly complicated with the discovery of multiple masses in a solitary kidney because any subsequent complications may result in a significant decline in quality of life.Particularly in the case of postoperative renal failure,dialysis becomes necessary.

  10. Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters

    Science.gov (United States)

    Wang, Hai-yi; Su, Zi-hua; Xu, Xiao; Sun, Zhi-peng; Duan, Fei-xue; Song, Yuan-yuan; Li, Lu; Wang, Ying-wei; Ma, Xin; Guo, Ai-tao; Ma, Lin; Ye, Hui-yi

    2016-01-01

    Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan–rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K trans & Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID:27380733

  11. Identification of a set of genes associated with response to interleukin-2 and interferon-α combination therapy for renal cell carcinoma through genome-wide gene expression profiling

    OpenAIRE

    MIZUMORI, OSAMU; Zembutsu, Hitoshi; Kato, Yoichiro; Tsunoda, Tatsuhiko; Miya, Fuyuki; Morizono, Takashi; Tsukamoto, Taiji; Fujioka, Tomoaki; Tomita, Yoshihiko; Kitamura, Tadaichi; Ozono, Seiichiro; Miki, Tsuneharu; Naito, Seiji; Akaza, Hideyuki; NAKAMURA, Yusuke

    2010-01-01

    Interleukin (IL)-2 and interferon (IFN)-α combination therapy for metastatic renal cell carcinoma (RCC) improves the prognosis for a subset of patients, while some patients suffer from severe adverse drug reactions with little benefit. To establish a method to predict responses to this combination therapy (approximately 30% response rate), the gene expression profiles of primary RCCs were analyzed using an oligoDNA microarray consisting of 38,500 genes or ESTs, after enrichment of the cancer ...

  12. Prognostic significance of survivin expression in renal cell cancer and its correlation with radioresistance.

    Science.gov (United States)

    Lei, Yu; Geng, Zhang; Guo-Jun, Wu; He, Wang; Jian-Lin, Yuan

    2010-11-01

    Survivin, an important inhibitor of apoptosis, has been found to play an important role in the initiation, progression, and chemoradioresistance of human malignancies. Previously, we have reported that upregulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance. The aim of this study was to assess prognostic significance of survivin protein expression in RCC and analyze its correlation with radiosensitivity of RCC cells. RT-PCR and Western blot assays were performed to detect survivin mRNA and protein expression in normal human kidney epithelial cell line (HKEC) or RCC cell lines. The expression of survivin mRNA in RCC and corresponding nontumor kidney tissues was also detected by RT-PCR. Immunohistochemistry was performed to determine survivin protein expression in 75 cases of RCC tissue samples. Moreover, the association of survivin protein expression with clinicopathogical factors and prognosis of RCC patients was statistically analyzed. Small interfering RNA was used to knockdown the endogenous survivin expression in RCC cell line (ACHN) and evaluate the effects of survivin knockdown on proliferation, apoptosis, and radiosensitivity of RCC cell line. RCC cells showed sufficient expression of survivin mRNA and protein, but the expression of survivin gene was not detected in normal HKEC. Moreover, the expression level of survivin mRNA in RCC tissues was significantly higher than that in corresponding nontumor kidney tissues. The immunostaining of survivin protein was mainly located in cytoplasm of RCC tumor cells. Tumor pathological stage (P = 0.028), grade (P = 0.004), and lymph node metastasis (P = 0.017) of RCC patients were significantly correlated with survivin protein expression. In addition, patients with high survivin levels had a significantly shorter overall survival than those with low levels (P < 0.001), and the expression of survivin protein was an independent prognostic factor for RCC patients (P = 0

  13. Evaluation of anti-apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Garg; Neeraj; K; Mangal; Sharad; Sahu; Tejram; Mehta; Abhinav; Vyas; Suresh; P; Tyagi; Rajeev; K

    2011-01-01

    Objective:To evaluate the anti-apoptotic and radical scavenging activities of dietary phenolics, namely ascorbic acid,a-tocopherol acetate,citric acid,salicylic acid,and estimate H2O2induced apoptosis in renal cell carcinoma cells.Methods:The intracellular antioxidant potency of antioxidants was investigated.H2O-2-induced apoptosis in RCC-26 was assayed with the following parameters:cell viability(%apoptosis),nucleosomal damage and DNA fragmentation, bcl-2 levels and flow cytometery analysis(ROS production evaluation).Results:Ine anticancer properties of antioxidants such as ascorbic acid,a- tocopherol acetate,citric acid,salicylic acid with perdurable responses were investigated.It was observed that these antioxidants had protective effect(anti-apoptotic activity) against hydrogen peroxide(H2O2) in renal cell carcinoma(RCC-26) cell line.Conclusions:This study reveals and proves the anticancer properties.However,in cancer cell lines anti-apoptotic activity can indirectly reflect the cancer promoter activity through radicals scavenging,and significantly protect nucleus and bcl-2.

  14. Retrospective Study of Metastatic Melanoma and Renal Cell Carcinoma to the Brain with Multivariate Analysis of Prognostic Pre-Treatment Clinical Factors

    Directory of Open Access Journals (Sweden)

    Ethan A. Ferrel

    2016-03-01

    Full Text Available Patients with brain metastasis from renal cell carcinoma (RCC or melanoma have historically had very poor prognoses of less than one year. Stereotactic radiosurgery (SRS can be an effective treatment for patients with these tumors. This study analyzes the effect of pretreatment prognostic factors on overall survival (OS for RCC and melanoma patients with metastasis to the brain treated with SRS. A total of 122 patients with brain metastases from either RCC or melanoma were grouped by age at brain metastasis diagnosis, whether they received whole brain radiation therapy (WBRT in addition to SRS, or they underwent surgical resection, Karnofsky Performance Score (KPS, number of brain metastases, and primary tumor. Median survival times for melanoma patients and RCC patients were 8.20 ± 3.06 and 12.70 ± 2.63 months, respectively. Patients with >5 metastases had a significantly shorter median survival time (6.60 ± 2.45 months than the reference group (1 metastasis, 10.70 ± 13.40 months, p = 0.024. Patients with KPS ≤ 60 experienced significantly shorter survival than the reference group (KPS = 90–100, with median survival times of 5.80 ± 2.46 months (p < 0.001 and 45.20 ± 43.52 months, respectively. We found a median overall survival time of 12.7 and 8.2 months for RCC and melanoma, respectively. Our study determined that a higher number of brain metastases (>5 and lower KPS were statistically significant predictors of a lower OS prognosis.

  15. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Valquiria Pessoa Chinem

    2011-04-01

    Full Text Available O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambiental associado a sua gênese. Entretanto, descrevem-se outros elementos de risco: fotótipos claros, idade avançada, história familiar de carcinomas de pele, olhos e cabelos claros, sardas na infância e imunossupressão, além de aspectos comportamentais, como exercício profissional exposto ao sol, atividade rural e queimaduras solares na juventude. Entre 30% e 75% dos casos esporádicos estão associados à mutação do gene patched hedgehog, mas outras alterações genéticas são ainda descritas. A neoplasia é comumente encontrada concomitantemente com lesões cutâneas relacionadas à exposição solar crônica, tais como: queratoses actínicas, lentigos solares e telangiectasias faciais. A prevenção do carcinoma basocelular se baseia no conhecimento de fatores de risco, no diagnóstico e tratamento precoces e na adoção de medidas específicas, principalmente, nas populações susceptíveis. Os autores apresentam uma revisão da epidemiologia do carcinoma basocelular.Basal cell carcinoma is the most common malignant neoplasm in humans and its incidence has increased over the last decades. Its high frequency significantly burdens the health system, making the disease a public health issue. Despite the low mortality rates and the rare occurrence of metastases, the tumor may be locally invasive and relapse after treatment, causing significant morbidity. Exposure to ultraviolet radiation is the main environmental risk factor

  16. ROLLER COMPACTED CONCRETE RCC UNTUK BANGUNAN BENDUNGAN

    Directory of Open Access Journals (Sweden)

    Handoko Sugiharto

    2003-01-01

    Full Text Available The using of Roller Compacted Concrete (RCC is one of many alternatives that can be used to decrease dam construction cost. Many Roller Compacted Concrete (RCC composition has been developed to achieve maximum compressive strength. Due to the economical consideration and the possibility of the execution, drop hammer system has been used for this research. Compression test is done after the age of the sample reaches seven, 28, 60, and 90 days. The result shows that 60/40 composition of gravel/sand has higher average compressive strength on all age of sample. The highest compressive strength the achieve is 17.78 MPa for 90 days sample. Abstract in Bahasa Indonesia : Penggunaan Roller Compacted Concrete (RCC merupakan salah satu alternatif yang dapat digunakan untuk mengurangi biaya pembuatan konstruksi bendungan. Berbagai komposisi benda uji Roller Compacted Concrete (RCC dibuat untuk mengetahui kuat tekan yang paling maksimal. Ditinjau dari segi ekonomis dan kemudahan pelaksanaan, maka digunakan sistem alat pemadat drop hammer. Dilakukan tes kuat tekan setelah umur benda uji masing-masing mencapai tujuh, 28, 60, dan 90 hari. Hasil penelitian menunjukkan bahwa komposisi kerikil/pasir sebesar 60/40 selalu memiliki kuat tekan rata-rata yang lebih tinggi pada semua umur benda uji. Kuat tekan terbesar pada benda uji umur 90 hari mencapai 17.78 MPa.

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

    Directory of Open Access Journals (Sweden)

    Quivy A

    2013-04-01

    Full Text Available Amandine Quivy,1,2 Amaury Daste,1 Asma Harbaoui,1 Sophie Duc,2,4 Jean-Christophe Bernhard,2,3 Marine Gross-Goupil,1 Alain Ravaud1,2 1Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital, Bordeaux, France; 2University of Bordeaux 2 (Victor Ségalen, Bordeaux, France; 3Department of Urology, Hôpital Pellegrin, Bordeaux University Hospital, Bordeaux, France; 4Department of Geriatrics, Hôpital Saint-André, Bordeaux University Hospital, Bordeaux, France Abstract: Both the aging population and the incidence of renal cell carcinoma (RCC are growing, making the question of tumor management in the elderly a real challenge. Doctors should be aware of the importance of assessing this specific subpopulation. An aggressive therapeutic approach may be balanced by the benefit of the treatment – care or cure – and the life expectancy and willingness of the patient. The treatment for local disease can be surgery (radical or partial nephrectomy or ablative therapies (radiofrequency, cryotherapy. Even if in most cases surgery is safe, complications such as alteration of renal function may occur, especially in the elderly, with physiological renal impairment at baseline. More recently, another option has been developed as an alternative: active surveillance. In the past decade, new drugs have been approved in the metastatic setting. All the phase 3 trials have included patients without a limit on age. Nevertheless, data concerning the elderly are still poor and concern only a very selective subpopulation. The toxicity profile of targeted agents may interfere with pre-existent comorbidities. Furthermore, the metabolism of several agents via cytochrome P450 can cause drug interaction. The importance of quality of life is a major factor with regard to management of therapy. Finally, to date, there is no recommendation of systematic a priori dose reduction in the elderly. In this review we describe the various possibilities of

  18. Large Cell Neuroendocrine Carcinoma of the Lung

    Directory of Open Access Journals (Sweden)

    Yusuf Aydemir

    2015-11-01

    Full Text Available Large-cell neuroendocrine carcinomas of the lung are extremely rare. There are difficulties related to the diagnosis and treatment and there are no consensus because of the small number of studies. 65-year-old male patient presented with hemoptysis. Chest X-ray and thoracic computorized tomography scan showed a mass lesion and it could not be diagnosed by bronchoscopic biopsy and lavage. Lobectomy was performed due to the high value of standardized uptake value in positron emission tomography. Large cell neuroendocrine carcinoma was diagnosed with pathological evaluation and immunohistochemical study and after 20-month follow-up there was no recurrence. The diagnosis, treatment, and prognosis of large cell neuroendocrine carcinoma in the light of the literature is presented.

  19. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    Science.gov (United States)

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed. PMID:24724463

  20. Rising incidence of Merkel cell carcinoma

    DEFF Research Database (Denmark)

    Lyhne, Dorte; Lock-Andersen, Jørgen; Dahlstrøm, Karin;

    2011-01-01

    Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investi......Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark...

  1. Basal Cell Carcinoma in a Child

    OpenAIRE

    Samet Vasfi Kuvat; Zuhal Gücin; Barış Keklik; Gülzade Özyalvaçlı; Karaca Başaran

    2011-01-01

    Basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is rarely encountered in the childhood period. An 11-year old child was admitted to our clinic due to an erythematous and a slightly pigmented lesion with a 3 × 4 cm diameter on his posterior scalp. Macroscopically, the lesion was excised with a 10 mm safety margin. Pathologic examination revealed a basal cell carcinoma. No symptoms or signs of a syndrome were observed both in the patient and his family.

  2. Basal Cell Carcinoma Arising in a Tattooed Eyebrow

    OpenAIRE

    Lee, Jong-Sun; Park, Jin; Kim, Seong-min; Yun, Seok-Kweon; Kim, Han-Uk

    2009-01-01

    Malignant skin tumors, including squamous cell carcinoma and malignant melanoma, have occurred in tattoos. Seven documented cases of basal cell carcinoma associated with tattoos have also been reported in the medical literature. We encountered a patient with basal cell carcinoma in a tattooed eyebrow. We report on this case as the eighth reported case of a patient with basal cell carcinoma arising in a tattooed area.

  3. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

    Science.gov (United States)

    Petersson, Fredrik; Grossmann, Petr; Hora, Milan; Sperga, Maris; Montiel, Delia Perez; Martinek, Petr; Gutierrez, Maria Evelyn Cortes; Bulimbasic, Stela; Michal, Michal; Branzovsky, Jindrich; Hes, Ondrej

    2013-07-01

    We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

  4. Basaloid squamous cell carcinoma involving floor of the mouth

    Directory of Open Access Journals (Sweden)

    Sah Kunal

    2008-01-01

    Full Text Available Basaloid squamous cell carcinomas of oral mucosa are uncommon. Majority of them can be differentiated from squamous cell carcinoma by their aggressive clinical course and their histopathological features. This case report presents a case of 70-year-old male with basaloid squamous cell carcinoma involving the floor of the mouth.

  5. The Plasma Membrane Sialidase NEU3 Regulates the Malignancy of Renal Carcinoma Cells by Controlling β1 Integrin Internalization and Recycling*

    Science.gov (United States)

    Tringali, Cristina; Lupo, Barbara; Silvestri, Ilaria; Papini, Nadia; Anastasia, Luigi; Tettamanti, Guido; Venerando, Bruno

    2012-01-01

    The human plasma membrane sialidase NEU3 is a key enzyme in the catabolism of membrane gangliosides, is crucial in the regulation of cell surface processes, and has been demonstrated to be significantly up-regulated in renal cell carcinomas (RCCs). In this report, we show that NEU3 regulates β1 integrin trafficking in RCC cells by controlling β1 integrin recycling to the plasma membrane and controlling activation of the epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK)/protein kinase B (AKT) signaling. NEU3 silencing in RCC cells increased the membrane ganglioside content, in particular the GD1a content, and changed the expression of key regulators of the integrin recycling pathway. In addition, NEU3 silencing up-regulated the Ras-related protein RAB25, which directs internalized integrins to lysosomes, and down-regulated the chloride intracellular channel protein 3 (CLIC3), which induces the recycling of internalized integrins to the plasma membrane. In this manner, NEU3 silencing enhanced the caveolar endocytosis of β1 integrin, blocked its recycling and reduced its levels at the plasma membrane, and, consequently, inhibited EGFR and FAK/AKT. These events had the following effects on the behavior of RCC cells: they (a) decreased drug resistance mediated by the block of autophagy and the induction of apoptosis; (b) decreased metastatic potential mediated by down-regulation of the metalloproteinases MMP1 and MMP7; and (c) decreased adhesion to collagen and fibronectin. Therefore, our data identify NEU3 as a key regulator of the β1 integrin-recycling pathway and FAK/AKT signaling and demonstrate its crucial role in RCC malignancy. PMID:23139422

  6. Collecting Duct Carcinoma With Cardiac Metastases: A Case Report & Literature Review

    Directory of Open Access Journals (Sweden)

    James N. Voss

    2016-03-01

    Full Text Available Collecting duct carcinoma (CDC, is a rare and aggressive form of renal cell carcinoma (RCC accounting for around 1% of all renal malignancy. It affects younger patients and is associated with rapid progression, distant spread and poor prognosis. Cardiac metastases from all types of RCC, without involvement of the inferior vena cava are very rare. We present the case of a 54 year old man with a history of CDC, who presents with collapse and ventricular tachycardia secondary to multifocal cardiac metastases. We are not aware of any other reports in the literature of CDC and cardiac metastases.

  7. Stem cell research in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chengyi SUN; Shi ZUO

    2008-01-01

    The traditional view that adult human liver tumors, mainly hepatocellular carcinoma (HCC), arise from mature cell types has been challenged in recent dec-ades. The results of several studies suggest that HCC can be derived from liver stem cells. There are four levels of cells in the liver stem cell lineage: hepatocytes, hepatic stem cells/oval cells, bone marrow stem cells and hepato-pancreas stem cells. However, whether HCC is resulted from the differentiation block of stem cells and, moreover, which liver stem cell lineage is the source cell of hepatocarcinogenesis remain controversial. In this review, we focus on the current status of liver stem cell research and their roles in carcinogenesis of HCC, in order to explore new approaches for stem cell therapy of HCC.

  8. Qualitative Spatial Reasoning in RCC8 with OWL and SWRL

    OpenAIRE

    Marc-Zwecker, Stella; De Bertrand De Beuvron, François; Zanni-Merk, Cecilia; Le Ber, Florence

    2013-01-01

    International audience The Region Connection Calculus (RCC), and particularly its RCC8 subset, have been extensively studied and used for qualitative spatial reasoning. Some sets of computational operations have also been defined for topological relations, as the CM8 set, that allows to compute the RCC8 relationships on raster images. In this paper, we propose a reified representation of the RCC8 spatial relationships and of the CM8 primitives, within a lattice of concepts, implemented in ...

  9. Ipsilateral synchronous renal pelvic transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    韩平; 魏强; 石明; 杨宇如

    2004-01-01

    @@ Reports of multiple synchronous primary renal neoplasms in the literature are rare. Although primary renal tumors of 2 distinctively dissimilar origins have been sporadically described,1-6 to our knowledge there have been no reported cases of triple primary renal neoplasms in the same kidney. Here we report a very rare case of ipsilateral synchronous renal pelvic transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma with marked hydronephrosis and multiple stones in the same kidney.

  10. Morphometric characteristics of basal cell carcinoma peritumoral stroma varies among basal cell carcinoma subtypes

    OpenAIRE

    Lesack Kyle; Naugler Christopher

    2012-01-01

    Abstract Background The role that the peritumoral stroma plays in the growth of tumours is currently poorly understood. In this manuscript the morphometric characteristics of basal cell carcinoma subtypes and their associated peritumoral stromas are presented. Methods Ninety eight digitized basal cell carcinoma histology slides were categorized as infiltrative, nodular, or superficial subtypes, and were analysed using a combination of manual and computer-assisted approaches. The morphometric ...

  11. Oesophageal squamous cell carcinoma in two cats

    International Nuclear Information System (INIS)

    Two cases of feline oesophageal squamous cell carcinoma are described. In both cases, diagnosis was achieved by radiography, endoscopy and cytology, and later confirmed by histology. One cat underwent oesophagectomy followed by end-to-end anastomosis, but died three days postsurgery; the second cat was euthanased after diagnosis

  12. The role of CXC-chemokine receptor CXCR2 and suppressor of cytokine signaling-3 (SOCS-3) in renal cell carcinoma

    International Nuclear Information System (INIS)

    Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC. In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases. Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis. Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its

  13. SCP, a polysaccharide from Schisandra chinensis, induces apoptosis in human renal cell carcinoma Caki-1 cells through mitochondrial-dependent pathway via inhibition of ERK activation.

    Science.gov (United States)

    Liu, Shi-Jian; Qu, Hai-Ming; Ren, Ye-Ping

    2014-06-01

    This study is the first to investigate the anticancer effect of Schisandra chinensis polysaccharide (SCP) in renal cell carcinoma (RCC) cells. The results revealed that SCP treatment showed high cytotoxic potency in Caki-1 cells by inducing apoptosis, which is associated with the disruption of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol, increase of Bax/Bcl-2 ratio, activation of caspase-3/9, and cleavage of poly(ADP-ribose) polymerase (PARP). Furthermore, pan-caspase inhibitor (z-VAD-fmk) significantly blocked SCP-induced apoptosis and PARP cleavage in Caki-1 cells. As well, we also observed that SCP inhibited the phosphorylation of ERK1/2, whereas it had no significant inhibition effect on the phospho-p38 and phospho-JNK activity. All the above parameters provided scientific evidence that SCP induced mitochondrial-mediated apoptosis in Caki-1 cells through the inactivation of ERK pathways, which may shed further light on its potential application as a cancer chemopreventive agent against RCC.

  14. Basal cell carcinoma in oculo-cutaneous albinism

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-06-01

    Full Text Available The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances. [Int J Res Med Sci 2016; 4(6.000: 2452-2454

  15. Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis

  16. Bilateral acrometastasis in a case renal cell carcinoma

    Science.gov (United States)

    Vaishya, Raju; Vijay, Vipul; Vaish, Abhishek

    2014-01-01

    We present a unique case of bilateral skeletal metastasis below the knee in a patient with renal cell carcinoma. In this rarest of rare cases, bony metastases were the first presentation of a primary tumour. Incidentally, the primary tumour (renal cell carcinoma) involved the solitary kidney of the patient and the same patient also had coexisting carcinoma of the prostate. PMID:25368128

  17. Suppression subtractive hybridization for identifying differentially expressed genes in renal cell carcinoma%肾癌差异表达基因的克隆及意义

    Institute of Scientific and Technical Information of China (English)

    张强; 辛殿旗; 那彦群; 郭应禄; 张志文

    2001-01-01

    目的克隆并鉴定肾癌与正常肾之间差异表达的基因,为研究肾癌发生发展的分子生物学机制奠定基础。 方法应用抑制性消减杂交技术(suppression subtractive hybridization, SSH),构建人肾癌组织与正常肾组织差异表达的cDNA消减文库,并从中克隆鉴定出肾癌差异表达的基因。 结果构建成功高消减效率的人肾癌组织cDNA消减文库,对其中10个克隆插入的cDNA片段进行测序后经GenBank检索表明10个片段均为未知新序列,其中RCC18为5个拷贝,这提示以上10个cDNA片段可能来自6个新基因。Northern blotting分析显示RCC18在肾癌组织中有明显表达,而在正常肾组织中无表达,这证明RCC18是肾癌特异表达的新基因。应用SMART RACE技术获得RCC18基因的全长。 结论人肾癌cDNA消减文库的建立为进一步大批量筛选、克隆肾癌特异性表达的未知新基因奠定了基础。初步筛选出的新基因为研究肾癌发生发展中的分子生物学机制提供了重要线索。%Objective To construct a renal cell carcinoma (RCC) cDNA subtractive library using suppression subtractive hybridization. Methods Polyadenylated RNA [Poly (A)+ RNA] was isolated from tissues of RCC and normal kidney, and single-strand cDNAs and double-strand cDNAs were synthesized in turn. RCC cDNAs were divided into two groups and ligated to the specific adaptors l and 2, and then hybridized with normal kidney cDNA twice with two rounds of suppression PCR. Second round PCR products were cloned to T/A plasmid vectors to set up the subtractive library. One hundred clones were randomly picked to perform enzyme digest analysis, and some underwent sequence analysis and Northern blot to identify RCC specifically expressed genes. SMART RACE procedure was operated to clone full length novel RCC specifically expressed genes. Results A human RCC subtractive library with high subtractive efficiency was successfully set

  18. Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

    Science.gov (United States)

    Farace, F; Gross-Goupil, M; Tournay, E; Taylor, M; Vimond, N; Jacques, N; Billiot, F; Mauguen, A; Hill, C; Escudier, B

    2011-01-01

    Background: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45dimCD34+VEGFR2+ progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45−CD31+CD146+7-amino-actinomycin (7AAD)− cells) were measured in 1 ml whole blood using four-color flow cytometry (FCM). Circulating CD45dimCD34+VEGFR2+7AAD− progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Pla