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Sample records for clear cell renal

  1. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

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    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.

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

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    Williamson, Sean R; Cheng, Liang

    2016-07-01

    Continued improvement of our understanding of the clinical, histologic, and genetic features of renal cell tumors has progressively evolved renal tumor classification, revealing an expanding array of distinct tumor types with different implications for prognosis, patient counseling, and treatment. Although clear cell renal cell carcinoma is unequivocally the most common adult renal tumor, there is growing evidence that some "clear cell" renal neoplasms, such as exemplified by multilocular cystic clear cell renal neoplasm of low malignant potential (formerly multilocular cystic renal cell carcinoma), do not have the same potential for insidious progression and metastasis, warranting reclassification as low malignant potential tumors or benign neoplasms. Still other novel tumor types such as clear cell papillary renal cell carcinoma have been more recently recognized, which similarly have shown a conspicuous absence of aggressive behavior to date, suggesting that these too may be recategorized as noncancerous or may be premalignant neoplasms. This importance for prognosis is increasingly significant in the modern era, in which renal masses are increasingly found incidentally by imaging techniques at a small tumor size, raising consideration for less aggressive management options guided by renal mass biopsy diagnosis, including imaging surveillance, tumor ablation, or partial nephrectomy. PMID:26988177

  3. 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.

  4. Genetic mutations associated with metastatic clear cell renal cell carcinoma

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    Wu, Qingjian; Li, Fengjie; Zhao, Jiang; Wu, Kaijin; Qu, Cunye; Chen, Yibu; Li, Meng; Chen, Xuelian; Stucky, Andres; Zhong, Jiangjian; Li, Longkun; Zhong, Jiang F.

    2016-01-01

    Metastasis is the major cause of death among cancer patients, yet early detection and intervention of metastasis could significantly improve their clinical outcomes. We have sequenced and analyzed RNA (Expression) and DNA (Mutations) from the primary tumor (PT), tumor extension (TE) and lymphatic metastatic (LM) sites of patients with clear cell renal cell carcinoma (CCRCC) before treatment. Here, we report a three-nucleotide deletion near the C-region of Plk5 that is specifically associated with the lymphatic metastasis. This mutation is un-detectable in the PT, becomes detectable in the TE and dominates the LM tissue. So while only a few primary cancer cells carry this mutation, the majority of metastatic cells have this mutation. The increasing frequency of this mutation in metastatic tissue suggests that this Plk5 deletion could be used as an early indicator of CCRCC metastasis, and be identified by low cost PCR assay. A large scale clinical trial could reveal whether a simple PCR assay for this mutation at the time of nephrectomy could identify and stratify high-risk CCRCC patients for treatments. PMID:26908440

  5. MET Inhibition in Clear Cell Renal Cell Carcinoma

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    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

  6. A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

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    2016-09-15

    Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma

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

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    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

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

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    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. Clear Cell Adenocarcinoma of the Renal Pelvis in a Male Patient

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    Sarawut Kongkarnka

    2013-01-01

    Full Text Available Carcinoma of the renal pelvis is an uncommon renal neoplasm. Clear cell adenocarcinoma in the urinary tract is rare and has a histomorphology resembling that of the female genital tract. We herein present a case of clear cell adenocarcinoma of the renal pelvis, which is the first example in a male patient to our knowledge. A 54-year-old man presented with right flank pain. The tumor was associated with renal stones and hydronephrosis and invaded into the peripelvic fat tissue with regional lymph node metastasis. The patient died of metastatic disease six months postoperatively. Histologically, the tumor showed complex papillary architecture lined with clear and hobnail cells. Clear cell adenocarcinoma of the renal pelvis may pose a diagnostic challenge on histological grounds, particularly in the distinction from renal cell carcinoma. The immunohistochemical stains could help confirm the diagnosis. Due to its rarity, an effective treatment regimen remains to be determined.

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

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    An Ren

    2015-01-01

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

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

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

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    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 ...

  13. Indium-111-labeled girentuximab immunoSPECT as a diagnostic tool in clear cell renal cell carcinoma

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

    2013-01-01

    BACKGROUND: Improved and more frequent radiologic evaluation has resulted in increased identification of renal masses of unknown origin, which frequently pose a diagnostic dilemma for urologists. OBJECTIVE: Carbonic anhydrase IX (CAIX) is an antigen ubiquitously expressed in clear cell renal cell ca

  14. Serial Pancreas, Liver and Duodenal Metastasis from Renal Clear Cell Cancer: a Case Report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Case Report In August 2004, a 76-year-old patient was referred to our hospital for progressive loss of appetite, accompanied with mild upper abdominal distention, pain, hiccups and dyspepsia over a recent 3 months period. Reviewing his disease history showed that 16 months before admission (April 2003), he was diagnosed with a recurring left renal clear cell cancer (immunohistochemical staining of tumor cells were positive for CK and Vim, but negative for SMA, HMB-45 and HHF-35, Fig. 1) 10 years after a nephrectomy due to a right renal cancer. At that time, he was treated with photodynamic therapy followed by bio-immunotherapy(interleukine-2 plus lymphokine-activated killer cells). Follow-up by an abdominal CT scan every 3 months showed significant regression of the left renal carcinoma.

  15. Clear cell renal cell carcinoma with hemangioblastoma-like features: A recently described pattern with unusual immunohistochemical profile

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    Sankalp Sancheti

    2015-01-01

    Full Text Available The diagnosis of clear cell renal cell carcinoma may sometimes pose challenges because of the presence of uncharacteristic morphology, varied immunophenotypic patterns and due to lack of molecular or genetic determinants. More often, the morphological variations can be easily overlooked in routine practice and a more common diagnosis is usually put forward. Solid, acinar and alveolar are the common patterns described in the literature. We report a recently described pattern of clear cell renal cell carcinoma which has hemangioblastoma-like morphology and an unusual immunoprofile. In our case, the tumor showed a diffuse hemangioblastoma-like pattern and diffuse positivity for Alpha-inhibin on immunohistochemistry. A thorough literature search, extensive sampling and an expanded immunohistochemistry panel revealed a clear cell renal cell carcinoma component. Presence of renal vein thrombosis and focal necrosis were other helpful features in discerning the malignant nature of tumor.

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

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    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.

  17. 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.

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

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    Dionigi Gianlorenzo

    2008-10-01

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

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

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    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

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

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    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

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

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    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...

  2. Skull Base Clear Cell Carcinoma, Metastasis of Renal Primary Tumor: A Case Report and Literature Review

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    Ilson Sepúlveda

    2013-08-01

    Full Text Available We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.

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

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    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...

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

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    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.)

  5. 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

  6. 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

  7. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

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    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  8. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

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

    OpenAIRE

    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...

  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. Contrast-enhanced ultrasound for detection and diagnosis of renal clear cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    DONG Xiao-qiu; SHEN Yi; XU Li-wei; XU Chun-mei; BI Wei; WANG Xiao-min

    2009-01-01

    Background Renal clear cell carcinoma (RCCC) is the most common malignant renal tumor. It is highly malignant,does not cause clinical symptoms in its eady stages, and cannot be diagnosed using conventional ultrasound. This study was aimed to investigate the contrast-enhanced ultrasound (CEUS) mode and characteristics of the time-intensity curve for RCCC and its pathological basis.Methods Forty-two patients with pathologically diagnosed RCCC underwent CEUS examination before surgery. The patients' kidneys were visualized after injection of contrast agents using the Technos MPX DU8. We analyzed the CEUS mode, time-intensity curve, and pathological findings.Results The detection rate of RCCC with conventional ultrasound was about 71%, while the rate using CEUS was 100%. Larger tumors (33 cases) showed non-uniform enhancement with defective filling. CEUS modes were divided into 4 types: type Ⅰ, "quick in and out" (26.19%, 11/42); type Ⅱ, "quick in and slow out" (40.48%, 17/42); type Ⅲ, "Simultaneous in and out" (16.67%, 7/42); and type Ⅳ "slow in and out" (16.67%, 7/42). All types had a close correlation to the pathological basis. "Time-intensity curve of CEUS consisted of 3 phases, the perfusion phase, regression phase, and lag phase. Cases of types Ⅰ and Ⅲ only had a perfusion and regression phase, those of type Ⅱ and Ⅳ had a perfusion phase,regression phase, and lag phase. Quantitative analysis of the time-intensity curve showed that the time-to-peak (TTP) of the lesions was shorter than that of normal renal parenchyma (P <0.0001), the mean value of the up slope rate of the absolute value of lesions was higher than that of the ipsilateral normal renal parenchyma (P <0.0001), and that the mean value of descent slope rate of the absolute value of lesions was lower than that of the ipsilateral normal renal parenchyma (P <0.0001).Conclusions CEUS is useful in detecting small vessels in tumors. Although there are several different CEUS modes,type

  12. 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.

  13. 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

  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. 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

  16. 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.

    Science.gov (United States)

    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.

  17. 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.

  18. 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

  19. 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.

  20. Genetic mutations in accordance with a low malignant potential tumour are not demonstrated in clear cell papillary renal cell carcinoma.

    Science.gov (United States)

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-06-01

    Clear cell papillary renal cell carcinoma (CCPRCC) cases were evaluated for mutations on the following genes: KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR. Four male and three female patients of age 42-74 years were evaluated. All cases were incidentally detected by ultrasound and ranged 1.8-3.5 cm. Microscopic examination showed variably tubulopapillary, tubular acinar, cystic architecture and the characteristic linear arrangement of nuclei. The cells were reactive with CK7 (strong), CA IX (cup-shape) and 34 β E12. CD10, AMACR/RACEMASE and GATA3 were negative. There were no mutations on any of the investigated genes. This preliminary observation supports the concept that CCPRCC might be indeed an indolent tumour worth it to be named as clear cell papillary neoplasm of low potential. PMID:26941183

  1. Ultrastructural appearance and cytoskeletal architecture of the clear, chromophilic, and chromophobe types of human renal cell carcinoma in vitro.

    OpenAIRE

    Gerharz, C D; Moll, R.; Störkel, S.; Ramp, U; Thoenes, W.; Gabbert, H E

    1993-01-01

    The clear, chromophilic, and chromophobe types of human renal cell carcinoma have been defined as distinct morphological entities and can be clearly separated by differences of ultrastructural appearance, cytoskeletal architecture, enzyme synthesis, and cytogenetic aberrations. In this report, the cytomorphological aspects of these tumor types are compared in vitro, showing that essential ultrastructural and cytoskeletal characteristics of each tumor type are expressed even after prolonged in...

  2. Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma

    Directory of Open Access Journals (Sweden)

    Alessandra Mangolini

    2014-01-01

    Full Text Available Renal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs, which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma.

  3. Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

    Directory of Open Access Journals (Sweden)

    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

  4. 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

  5. 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.

  6. Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of clear cell renal cell carcinoma.

    Science.gov (United States)

    Zhao, Ziyi; Chen, Changjin; Lin, Junzhi; Zeng, Wentong; Zhao, Juan; Liang, Yindan; Tan, Qinrui; Yang, Chao; Li, Hui

    2016-09-01

    The von Hippel-Lindau tumor suppressor (VHL; E3 ubiquitin ligase gene) is frequently mutated or undetectable in clear cell renal cell carcinoma (CCRCC), and therefore these tumors are highly resistant to chemotherapeutic agents, including adriamycin (ADM) and sunitinib. A mutation in the tumor protein p53 (TP53) also leads to chemoresistance in tumors; however, in CCRCC, TP53 is frequently functional, yet the tumors remain highly insensitive to chemotherapy. This indicates the possibility of a synergistic effect of VHL and P53 in CCRCC. The present study aimed to detect the chemosensitivity of CCRCC. The expression of VHL in the MZ1257 cell line sensitized these cells to ADM and sunitinib, and a knockdown of VHL in the ACHN cells increased their chemoresistance. To confirm that VHL and P53 are both required for chemosensitivity, VHL and P53 were co‑expressed in 786‑O cells. The results of the functional antagonist assay (which assessed the IC50 values, i.e. the half maximal inhibitory concentration) confirmed that VHL and P53 act in synergy to promote chemosensitivity. Cell cycle arrest was measured by propidium iodide staining following treatment with ADM or sunitinib. Further analysis indicated that co‑expression of VHL and P53 inhibited cell proliferation by completely inhibiting the cell cycle at the G0/G1 phase, and promoted apoptosis following treatment with ADM or sunitinib. These findings demonstrated that VHL and P53 act synergistically in the regulation of cell proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles in the regulation of cell proliferation and apoptosis in CCRCC. Furthermore, the regulatory role of VHL is dependant on the activation P53. PMID:27485825

  7. 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

  8. 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

  9. 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

  10. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

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    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  11. Ultrastructural appearance and cytoskeletal architecture of the clear, chromophilic, and chromophobe types of human renal cell carcinoma in vitro.

    Science.gov (United States)

    Gerharz, C D; Moll, R; Störkel, S; Ramp, U; Thoenes, W; Gabbert, H E

    1993-03-01

    The clear, chromophilic, and chromophobe types of human renal cell carcinoma have been defined as distinct morphological entities and can be clearly separated by differences of ultrastructural appearance, cytoskeletal architecture, enzyme synthesis, and cytogenetic aberrations. In this report, the cytomorphological aspects of these tumor types are compared in vitro, showing that essential ultrastructural and cytoskeletal characteristics of each tumor type are expressed even after prolonged in vitro cultivation. The pattern of intermediate filament proteins of each tumor type was preserved in vitro, permitting the separation of exclusively cytokeratin-positive chromophobe tumor cells from clear and chromophilic tumor cells with a co-expression of vimentin and cytokeratins. In vitro, the chromophobe tumor cells continued to exhibit abundant cytoplasmatic microvesicles and sparsely distributed "studded" vesicles, which are known to be characteristic features of this tumor type in vivo. This observation confirmed the structural similarity of the chromophobe cell to the 'intercalated cell' of the cortical collecting duct and provided further evidence for the histogenetic derivation of this tumor subtype from the collecting duct system.

  12. ERK5/BMK1 Is a Novel Target of the Tumor Suppressor VHL: Implication in Clear Cell Renal Carcinoma

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    Laura Arias-González

    2013-06-01

    Full Text Available Extracellular signal-regulated kinase 5 (ERK5, also known as big mitogen-activated protein kinase (MAPK 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas.

  13. 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

  14. 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.

  15. 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.

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    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.

  16. 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

  17. Prognostic impact of epidermal growth factor receptor on clear cell renal cell carcinoma: Does it change with different expression patterns?

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    Duygu Kankaya

    2016-01-01

    Full Text Available Introduction: The aim of this study was to assess whether epidermal growth factor receptor (EGFR overexpression was a significant prognostic factor in clear cell renal cell carcinoma (CRCC and whether its prognostic significance was affected by immunohistochemical expression patterns. Materials and Methods: Immunohistochemistry was performed on 100 cases of CRCC using an antibody against EGFR. Tumors were grouped by nuclear grade (NG as low-NG (NG1, 2 or high NG (NG3, 4, and by pathological stage as localized (pT1, 2, or locally invasive (pT3, 4. Clinical disease was grouped by clinical stage as early stage (stage I, II, or late stage (stage III, IV. Evaluation of the EGFR overexpression was based on cytoplasmic (EGFR Cyt , and membranous (EGFR Mem staining. Results: EGFR Cyt correlated with high NG (P = 0.001, lymphovascular invasion (P = 0.028, regional lymph node involvement (P = 0.027, metastasis (P = 0.001, late stage (P = 0.003, cancer-specific death (P = 0.036, and was a predictor for disease-specific survival (P = 0.012 whereas EGFR Mem correlated with only local invasion (P = 0.021 and perirenal invasion (P = 0.009 and did not show any correlation with cancer-specific death or disease specific survival. Conclusion: Our findings suggest that EGFR overexpression is an important prognostic factor in CRCC, and its prognostic value differs significantly with respect to the location of EGFR immunostaining. This prognostic difference may give direction on the management and treatment of CRCC patients.

  18. Differing von Hippel Lindau genotype in paired primary and metastatic tumors in patients with clear cell renal cell carcinoma

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    Susan A.J. Vaziri

    2012-05-01

    Full Text Available In sporadic clear cell renal cell carcinoma (CCRCC, the von Hippel Lindau (VHL gene is inactivated by mutation or methylation in the majority of primary (P tumors. Due to differing effects of wild-type (WT and mutant (MT VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization (CGH analysis studies have reported genetic differences between paired P and metastatic (M tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients to determine a possible clonal relationship between the P tumor and M lesion(s in patients with CCRCC. Using paraffin embedded specimens, genomic DNA from microdissected samples (>80% tumor of paired P tumor and M lesions from all 10 patients, as well as in normal tissue from 6 of these cases, was analyzed. The DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene. Sequences derived from amplified samples were compared to the wild-type VHL gene sequence (GeneBank Accession No. AF010238. Methylation status of the VHL gene was determined using VHL methylation-specific PCR primers after DNA bisulfite modification. In 4/10 (40% patients the VHL gene status differed between the P tumor and the M lesion. As expected, when the VHL gene was mutated in both the P tumor and M lesion, the mutation was identical. Further, while the VHL genotype differed between the primary tumor in different kidneys or multiple metastatic lesions in the same patient, the VHL germline genotype in the normal adjacent tissue was always wild-type irrespective of the VHL gene status in the P tumor. These results demonstrate for the first time that the VHL gene status can be different between paired primary and metastatic tissue in patients with CCRCC.

  19. Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

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    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.

  20. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

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    Yan Song

    2015-01-01

    Full Text Available Background: Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC, but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL gene status, vascular endothelial growth factor receptor (VEGFR or stem cell factor receptor (KIT expression, and their relationships with characteristics and clinical outcome of advanced ccRCC. Methods: A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS and overall survival (OS were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses. Results: Of 59 patients, objective responses were observed in 28 patients (47.5%. The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6% had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%. VHL mutation status did not correlate with either overall response rate (P = 0.938 or PFS (P = 0.277. The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043. Conclusion

  1. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Song; Jing Huang; Ling Shan; Hong-Tu Zhang

    2015-01-01

    Background:Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC),but biomarkers of activity are lacking.The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status,vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression,and their relationships with characteristics and clinical outcome of advanced ccRCC.Methods:A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute,Chinese Academy of Medical Sciences between January 2010 and November 2012.Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry.Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and ovcrall survival (OS) were calculated and then compared based on expression status.The Chi-square test,the KaplanMeier method,and the Lon-rank test were used for statistical analyses.Results:Of 59 patients,objective responses were observed in 28 patients (47.5%).The median PFS was 13.8 months and median OS was 39.9 months.There was an improved PFS in patients with the following clinical features:Male gender,number of metastatic sites 2 or less,VEGFR-2 positive or KIT positive.Eleven patients (18.6%) had evidence of VHL mutation,with an objective response rate of 45.5%,which showed no difference with patients with no VHL mutation (47.9%).VHL mutation status did not correlate with either overall response rate (P =0.938) or PFS (P =0.277).The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients,respectively,which was significantly longer than that of VEGFR-2 or KIT negative patients (P =0.026 and P =0.043).Conclusion:VHL mutation status could not predict

  2. Correlation between apparent diffusion coefficient value and pathological grading in pT1b clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the correlation of ADC values on 3.0 T MR with the pathological grades in pT1b clear cell renal cell carcinoma (CCRCC). Methods: Conventional MR images, ADC values and Fuhrman pathological grading of pT1b CCRCC were performed in 30 patients. Grade Ⅰ and Ⅱ were defined as low-grade group; grade Ⅲ and Ⅳ were defined as high-grade group. The differences of ADC values among four different pathologic grades were compared with a one-way analysis of variance. The comparison of ADC values of two different grade groups was performed with t test, and the ROC curve was performed to evaluate the diagnostic efficacy of ADC value. Correlation between pathological grading and ADC values was assessed with Spearman rank correlation analysis. Results: (1) The mean ADC value of grading Ⅰ (10 patients), Ⅱ (8 patients), Ⅲ (7 patients), Ⅳ (5 patients) was (0.94 ± 0.11) ×10-3 mm2/s, (0.82 ±0.13) × 10-3 mm2/s,(0.68 ±0.09) × 10-3 mm2/s, (0.59 ±0.03) × 10-3 mm2/s, respectively. Significant differences of ADC values among the four grades were present (F=16.422, P=0.000). (2) The mean ADC value of the low-grade group was significantly higher than that of the high-grade group (t=5.738, P=0.000). Sensitivity and specificity of diagnosing the low-grade group was 88.9% and 83.3% respectively. There was a negative correlation between pathological grading and ADC value (r=-0.807, P<0.05). Conclusions: The ADC values of pT1b CCRCC have close correlation with pathological grading. They can be used to predict the degree of tumor malignancy preoperatively and guide surgical planning. (authors)

  3. 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

  4. 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

  5. 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

  6. 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

  7. Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma

    Science.gov (United States)

    Zeng, Fan-Chang; Zeng, Ming-Qiang; Huang, Liang; Li, Yong-Lin; Gao, Ben-Min; Chen, Jun-Jie; Xue, Rui-Zhi; Tang, Zheng-Yan

    2016-01-01

    Objective The aim of this study was to investigate the effects of vascular endothelial growth factor A (VEGFA) on cell proliferation, apoptosis, migration, and invasion in renal clear cell carcinoma (RCCC). Methods Between June 2012 and June 2015, RCCC tissues were obtained for the experimental group, and RCCC adjacent tumor-free kidney parenchyma tissues were obtained for the control group. VEGFA mRNA and protein expressions and phosphoinositide 3-kinase, serine/threonine-specific protein kinase (AKT), and phosphorylated-AKT protein expressions were detected. The chemically synthesized specific siRNA using RNA interference technology was used to inhibit VEGFA gene expression in human RCCC 786-O cells. The negative control (NC) group was transfected with NC sequence, and the blank group was transfected with no sequence. Flow cytometry, scratch test, and cell-penetrating experiment were used to detect cell proliferation, apoptosis, migration, and invasion of 786-O cells. Results Positive expression of VEGFA protein was 60.62% in RCCC tissue and 18.34% in adjacent tissue with statistically significant difference (P<0.001). VEGFA protein and mRNA expressions were higher in RCCC tissue than those in adjacent tissue (both P<0.01). VEGF expression in RCCC tissue was associated with Fuhrman grading and American Joint Committee on Cancer staging (both P<0.05). After RCCC 786-O cells transfecting the VEGFA siRNA, the VEGFA mRNA and protein expressions and phosphoinositide 3-kinase and phosphorylated-AKT protein expressions were significantly decreased, cell proliferation was remarkably inhibited, cell apoptotic ratio was obviously increased, and migration distance and invasive cell number were markedly decreased compared to those in the NC group and the blank group (all P<0.05). Conclusion Inhibition of VEGFA inhibited proliferation, promoted apoptosis, and suppressed migration and invasion of RCCC 786-O cells. VEGF has a potential role in diagnosis and therapy of RCCC

  8. MOLECULAR GENETIC DISORDERS IN THE VHL GENE AND METHYLATION OF SOME SUPPRESSOR GENES IN SPORADIC CLEAR-CELL RENAL CARCINOMAS

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    D. S. Mikhailenko

    2014-07-01

    Full Text Available Renal carcinoma (RC is one of ten most common malignancies in adults and an urgent problem of modern oncology. The purpose of the study was to make a molecular genetic analysis of a number of suppressor genes in RC, which was aimed at searching for and characterizing the potential markers of the disease. Two hundred and nine RC samples were examined, of them there were 192 clear-cell carcinomas. VHL gene mutations were detected by single-strand conformation polymorphism and sequence analyses while the methylation of suppressor genes was by the methylation-sensitive polymerase chain reaction. Somatic VHL mutations were determined in 35.4% of cases of clear-cell RC (CCRC. VHL gene disorders were found in 53.7% of patients with Stage 1, which counts in favor of VHL inactivation in early-stage CCRC. The methylation of the VHL, RASSF1, FHIT, and CDH1 genes was identified in 12, 56, 58.4, and 46.4% of primary tumors, respectively; that of at least one gene was in 84.1% of the samples. The hypermethylation of the RASSF1 gene was associated with late stages (p = 0.015 and the presence of metastases (p = 0.036; that of the CDH1 gene was related to the progression, invasion, and dissemination of primary tumors (p = 0.009, 0.039, and 0.002, respectively. The findings show it possible to use an analysis of abnormalities in the VHL gene and the methylation of the RASSF1 and CDH1 genes to develop a system of molecular genetic markers of RC.

  9. Analysis of Pathological Diagnosis of Renal Clear Cell Carcinoma%肾脏透明细胞癌的病理诊断分析

    Institute of Scientific and Technical Information of China (English)

    杜晓敏

    2015-01-01

    Objective To investigate the pathological diagnosis of renal clear cell carcinoma. Methods The 163 patients were re-garded as research subjects, which pathological diagnosis of renal clear cell carcinoma in Pathology from 2011 January to 2014 June, and the pathological data were retrospectively analyzed. Results In 163 patients, renal clear cell carcinoma grade I 56 cases, accounting for 34.4%, renal cell carcinoma 43 cases, accounting for 26.4%, clear cell renal III 35 cases, accounting for 21.5%, re-nal clear cell carcinoma grade IV 29 cases, accounting for 17.7%. Under microscope, tumor cells larger, circular or polygonal, abundant cytoplasm, transparent, full of interstitial capillaries and sinuses. Conclusion The pathological diagnosis was observed under microscope in tissue structure and cell lesion characteristics and disease diagnosis made, Renal clear cell carcinoma is the most common malignant tumor, renal cell carcinoma with good prognosis, early pathological diagnosis analysis, can greatly improve the quality of life of the patients.%目的:探讨肾脏透明细胞癌的病理诊断分析。方法整群选取2011年1月-2014年6月在该病理科进行肾脏透明细胞癌的病理诊断的163例患者作为研究对象,并对其病理资料进行回顾性分析。结果163例患者中,肾透明细胞癌玉级56例,占34.4%,肾透明细胞癌Ⅱ级43例,占26.4%,肾透明细胞芋级35例,占21.5%,肾透明细胞癌Ⅳ级29例,占17.7%。镜下可见肿瘤细胞体积较大,圆形或多边形,胞质丰富,透明状,间质富有毛细血管和血窦。结论病理诊断是在镜下观察组织结构和细胞病变特征而做出的疾病诊断,肾脏透明细胞癌是肾癌中最常见的恶性肿瘤,预后较好,及早进行病理诊断分析,可以大大的提高患者的生活质量。

  10. Integrative genome-wide analysis of the determinants of RNA splicing in kidney renal clear cell carcinoma.

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    Lehmann, Kjong-Van; Kahles, André; Kandoth, Cyriac; Lee, William; Schultz, Nikolaus; Stegle, Oliver; Rätsch, Gunnar

    2015-01-01

    We present a genome-wide analysis of splicing patterns of 282 kidney renal clear cell carcinoma patients in which we integrate data from whole-exome sequencing of tumor and normal samples, RNA-seq and copy number variation. We proposed a scoring mechanism to compare splicing patterns in tumor samples to normal samples in order to rank and detect tumor-specific isoforms that have a potential for new biomarkers. We identified a subset of genes that show introns only observable in tumor but not in normal samples, ENCODE and GEUVADIS samples. In order to improve our understanding of the underlying genetic mechanisms of splicing variation we performed a large-scale association analysis to find links between somatic or germline variants with alternative splicing events. We identified 915 cis- and trans-splicing quantitative trait loci (sQTL) associated with changes in splicing patterns. Some of these sQTL have previously been associated with being susceptibility loci for cancer and other diseases. Our analysis also allowed us to identify the function of several COSMIC variants showing significant association with changes in alternative splicing. This demonstrates the potential significance of variants affecting alternative splicing events and yields insights into the mechanisms related to an array of disease phenotypes.

  11. 18-F fluorodeoxyglucose uptake in positron emission tomography as a pathological grade predictor for renal clear cell carcinomas

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    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.)

  12. CLINICAL VALUE OF THE MARKERS OF PROLIFERATION AND APOPTOSIS IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

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    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. 

  13. Body Mass Index and von Hippel-Lindau Gene Mutations in Clear-cell Renal Cancer: Results of the Netherlands Cohort Study on Diet and Cancer

    NARCIS (Netherlands)

    Smits, K.M.; Schouten, L.J.; Hudak, E.; Verhage, B.; Dijk, B.A.C. van; Hulsbergen - Kaa, C.A. van de; Goldbohm, R.A.; Oosterwijk, E.; Brandt, P.A. van den

    2010-01-01

    Purpose: Body mass index (BMI) is an important risk factor for clear-cell renal cancer (cc-RCC). A common molecular alteration in cc-RCC is loss-of-function of the von Hippel-Lindau (VHL) gene. We evaluated the association between BMI and VHL mutations in cc-RCC by using data from the Netherlands Co

  14. 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.

  15. 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

  16. Pomegranate extract inhibits EMT in clear cell renal cell carcinoma in a NF-κB and JNK dependent manner

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    Jiabin An

    2015-01-01

    Conclusion: These findings suggest that PE may mediate inhibition growth of pVHL-deficient ccRCCs and raises the possibility of its use as a dietary adjunct to managing patients with active surveillance for small, localized, incidentally identified renal tumors so as to avoid more invasive procedures such as nephrectomy.

  17. Emergency Pancreatoduodenectomy with Preservation of Gastroduodenal Artery for Massive Gastrointestinal Bleeding due to Duodenal Metastasis by Clear Cell Renal Cell Carcinoma in a Patient with Celiac Artery Stenosis

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    Kyriakos Neofytou

    2014-01-01

    Full Text Available Duodenal metastasis from renal cell carcinoma is rare, and even rarer is a massive gastrointestinal bleeding from such tumours. Coeliac occlusive disease, although rarely symptomatic, can lead to ischaemic changes with anastomotic dehiscence and leaks when a patient undergoes pancreatoduodenectomy. A 41-year-old man with known metastasis to the adrenal glands and the second part of the duodenum close to the ampulla of Vater from clear cell renal cell carcinoma was admitted to our department due to massive gastrointestinal bleeding from the duodenal metastasis. Endoscopic control of the bleed was not possible, while the bleeding vessel embolization was able to control the haemorrhage only temporarily. An angiography during the embolization demonstrated the presence of stenosis of the coeliac artery and also hypertrophic inferior pancreaticoduodenal arteries supplying the proper hepatic artery via the gastroduodenal artery (GDA. The patient underwent emergency pancreatoduodenectomy with preservation of the gastroduodenal artery. The patient had an uneventful recovery and did not experience further bleeding. Also the blood flow to the liver was compromised as shown by the normal liver function tests (LFTs postoperatively. To the best of our knowledge, this is the first report of a preservation of the GDA during an emergency pancreatoduodenectomy.

  18. Evaluation of the efficiency of combination palliative treatment in patients with metastatic clear-cell renal cell carcinoma

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    P. S. Borisov

    2015-01-01

    Full Text Available Background. Experience with combination treatment, i.e. systemic therapy in combination with palliative surgery, in the treatment of metastatic kidney cancer is very rarely described in world literature.Objective: to evaluate the efficiency of combination treatment in combination with palliative cytoreductive surgery and targeted therapy and to define optimal indications for combination treatment.Subjects and methods. Data on 47 patients with metastatic renal cell carcinoma (mRCC who received systemic (targeted therapy in combination or after incomplete cytoreduction (iCR were analyzed in this retrospective study. The proportion of men and women was 72.3 % and 27.7 %, respectively; their ratio was 2.6:1. All the patients (100% underwent surgical treatment as nephrectomy or kidney resection for primary tumor. In the patients who had received radical treatment in different periods, the median relapse-free survival was 25.3 (0-187 months; the mean follow-up duration in the study was 33.2 (27.4–39.0 months. Out of the histological characteristics of a primary tumor, its Fuhrman grade was studied. Prior to initiation of mRCC therapy, Memorial Sloan Kettering Cancer Center (MSKCC prognosis groups were assessed; the patients were divided into good (n = 9 (19.1 %, interim (n = 28 (59.6 %, and bad (n = 10 (21.3 % prognosis groups. Their total somatic status was separately rated using the ECOG scale: 0, (n = 10 (21.3%, 1 (n = 24 (51.1 %, and 2, (n = 13 (27.6 %. The sites of metastases were as follows: the lung (n = 29, bones (n = 18, adrenals (n = 11, recurrence in the removed kidney bed (n = 10, and liver (n = 10. Multiple organ involvements were detected in 22 (46.8 % patients. There were more than 5 metastases in one organ in 18 (40.0 % patients and only 15 (33.3 % were found to have a single focus in one organ. Whether iCR might be used as a separate line treatment was studied. A comparative analysis was made between 2 groups of

  19. 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

  20. 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.

  1. 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.

  2. Clear cell chondrosarcoma

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    Kumar, R.; David, R.; Cierney, G. III

    1985-01-01

    The clinical, radiologic, and histopathologic features of three cases of clear cell chondrosarcoma are described. On radiographs, this rather benign-appearing tumor resembles a chondroblastoma when it occurs at the end of a long bone, and may occasionally show a calcified matrix. However, it has distinctive tumor cells with a centrally placed vesicular nucleus surrounded by clear cytoplasm. The lesion has a low-grade malignancy and is amenable to en bloc surgical resection, which results in a much better prognosis than that of conventional chondrosarcoma.

  3. Tumor-specific hypermethylation of epigenetic biomarkers, including SFRP1, predicts for poorer survival in patients from the TCGA Kidney Renal Clear Cell Carcinoma (KIRC project.

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    Christopher J Ricketts

    Full Text Available The recent publication of the TCGA Kidney Renal Clear Cell Carcinoma (KIRC project has provided an immense wealth and breadth of data providing an invaluable tool for confirmation and expansion upon previous observations in a large data set containing multiple data types including DNA methylation, somatic mutation, and clinical information. In clear cell renal cell carcinoma (CCRCC many genes have been demonstrated to be epigenetically inactivated by promoter hypermethylated and in a small number of cases to be associated with clinical outcome. This study created two cohorts based on the Illumina BeadChip array used to confirm the frequency of tumor-specific hypermethylation of these published hypermethylated genes, assess the impact of somatic mutation or chromosomal loss and provide the most comprehensive assessment to date of the association of this hypermethylation with patient survival. Hypermethylation of the Fibrillin 2 (FBN2 gene was the most consistent epigenetic biomarker for CCRCC across both cohorts in 40.2% or 52.5% of tumors respectively. Hypermethylation of the secreted frizzled-related protein 1 (SFRP1 gene and the basonuclin 1 (BNC1 gene were both statistically associated with poorer survival in both cohorts (SFRP1 - p = <0.0001 or 0.0010 and BNC1 - p = <0.0001 or 0.0380 and represented better independent markers of survival than tumor stage, grade or dimension in one cohort and tumor stage or dimension in the other cohort. Loss of the SFRP1 protein can potentially activate the WNT pathway and this analysis highlighted hypermethylation of several other WNT pathway regulating genes and demonstrated a poorer survival outcome for patients with somatic mutation of these genes. The success of demethylating drugs in hematological malignances and the current trials in solid tumors suggest that the identification of clinically relevant hypermethylated genes combined with therapeutic advances may improve the effectiveness and

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

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    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.

  5. 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.

  6. 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

  7. 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

  8. Diagnosis value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Objective: To explore the diagnostic value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma. Methods: Sixty patients who were suspected of clear cell renal cell carcinoma underwent non-enhanced CT and contrast enhancement CT of early interface-phase between cortex -medulla and parenchymal phase on a dual-energy CT. The true non-enhanced kidney CT (TNCT) was performed in a single-energy acquisition mode, but the dual-phase contrast enhancement CT were performed in a dual-energy mode of 80 kV and 140 kV respectively. The virtual non-enhanced CT (VNCT) images were derived from the data of early interface phase using liver virtual non-contrast software. The diagnose according to VNCT combined dual-phase contrast enhancement CT and dual-phase contrast enhancement CT only were made respectively and compared with χ2 test. Between the true non-contrast CT and the virtual non-contrast CT, the image quality was compared with Wilcoxon test; The radiation dose of volume CT dose index (CTDIvol) and dose length product(DLP) in a single-phase and total examination, the mean CT HU values of the tumours were compared with t test. Results: The accuracy of VNCT combined dual-phase contrast enhancement CT was higher than that of dual-phase contrast enhancement CT only [93.3% (56/60) vs.78.3% (47/60); χ2=5.6, P<0.05]. The detective ability (score) of VNCT was near to that of TNCT and the difference was not obvious (Z=0.00, P>0.05). The radiation dose of volume CT dose index (CTDIvol) and dose length product (DLP) in a single phase and total examination of VNCT [(8.85 ± 1.28) mGy, (196.45 ±21.12) mGy·cm, (17.69±2.35) mGy, (392.90±42.25) mGy · cm] were lower than that of TNCT [(10.20 ± 1.44) mGy,(218.29 ± 29.60) mGy · cm, (30.61 ± 3.27) mGy and (654.86 ± 88.81) mGy ·cm], t=4.21, 3.58, 23.63, 16.12 respectively, P<0.05. The mean CT HU values of tumours on VNCT images was higher than that on

  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. 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

  11. Differentiation of Renal Clear Cell Carcinoma:Evaluation with CT Spectral Imaging%CT能谱成像评价肾透明细胞癌核分级

    Institute of Scientific and Technical Information of China (English)

    赵娜; 程琦

    2014-01-01

    Purpose CT spectroscopy imaging was used in the preoperative differentiation evaluation of renal clear cell carcinoma, to access its malignant degree preoperatively, and to guide the operation treatment. Materials and Methods The spectral characteristics of 40 patients with renal clear cell carcinoma (RCCC) were analyzed retrospectively, all the RCCC patients underwent gemstone spectral imaging (GSI) scans, to obtain spectral serial images for the arterial phase and medulla phase. Spectral characteristic parameters and spectrum curve between different grades of renal cell carcinoma was compared, and the results were compared with pathology. Results Among the 40 cases of patients, carcinoma of grade I, II and III were 13 cases, 15 cases and 12 cases respectively. CT value ratio of renal clear cell carcinoma of grade I, II and III under 70 keV were 1.17±0.25, 0.84±0.85 and 0.64±0.19 (F=23.697, P0.05). Conclusion The differences of CT value, energy spectrum curve slope, iodine value under CT spectroscopy single energy imaging between renal clear cell carcinoma with different nuclear grade were statistically signiifcant, which can be expected to provide the basis for preoperative therapy selection.%目的:采用CT能谱成像术前评估肾透明细胞癌核分级,以评估术前肾透明细胞癌的恶性程度,指导手术治疗。资料与方法回顾性分析经手术病理证实的40例肾透明细胞癌肿块的能谱特征,所有患者术前均采用64层CT能谱的能谱扫描模式进行扫描,获得动脉期和髓质期的能谱系列图像。比较不同分级肾透明细胞癌的能谱特征参数及能谱曲线,并与病理结果进行对照。结果40例患者中,I、II、III级分别有13例、15例、12例。肾透明血细胞癌I、II、III级动脉期70 keV CT值比值分别为1.17±0.25、0.84±0.85、0.64±0.19(F=23.697, P0.05)。结论 CT能谱成像扫描参数单能量CT值、能谱曲线斜率、碘基值在肾透明细胞

  12. Von Hippel-Lindau (VHL inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

    Directory of Open Access Journals (Sweden)

    Lee E Moore

    2011-10-01

    Full Text Available Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs. VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5. Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31 and current: OR = 0.56 (0.32-0.99; P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.

  13. 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

  14. Transcriptome Sequencing (RNAseq) Enables Utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development

    Science.gov (United States)

    Eikrem, Oystein; Beisland, Christian; Hjelle, Karin; Flatberg, Arnar; Scherer, Andreas; Landolt, Lea; Skogstrand, Trude; Leh, Sabine; Beisvag, Vidar; Marti, Hans-Peter

    2016-01-01

    Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1)-regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data

  15. Transcriptome Sequencing (RNAseq Enables Utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development.

    Directory of Open Access Journals (Sweden)

    Oystein Eikrem

    Full Text Available Formalin-fixed, paraffin-embedded (FFPE tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany stored samples from clear cell renal cell carcinoma (ccRCC patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106 differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9, neuronal pentraxin-2 (NPTX2 and uromodulin (UMOD that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1-regulated genes, epithelial to mesenchymal transition (EMT and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study

  16. Transcriptome Sequencing (RNAseq) Enables Utilization of Formalin-Fixed, Paraffin-Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development.

    Science.gov (United States)

    Eikrem, Oystein; Beisland, Christian; Hjelle, Karin; Flatberg, Arnar; Scherer, Andreas; Landolt, Lea; Skogstrand, Trude; Leh, Sabine; Beisvag, Vidar; Marti, Hans-Peter

    2016-01-01

    Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1)-regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data

  17. 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.

  18. 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

  19. 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

  20. Prognostic significance of multidrug-resistance protein (MDR-1) in renal clear cell carcinomas: A five year follow-up analysis

    International Nuclear Information System (INIS)

    A large number of renal cancer patients shows poor or partial response to chemotherapy and the mechanisms have not been still understood. Multi-drug resistance is the principal mechanism by which many cancers develop resistance to chemotherapic drugs. The role of the multi-drug resistant transporter (MDR-1/P-glycoprotein), the gene product of MDR-1, and that one of the so-called multi-drug resistance associated protein (MRP), two energy-dependent efflux pumps, are commonly known to confer drug resistance. We studied MDR-1 expression in selected cases of renal cell carcinoma (RCC), clear cell type, with long-term follow-up, in order to establish its prognostic role and its possible contribution in the choice of post-surgical therapy. MDR-1 has been studied by standard LSAB-HRP immunohistochemical technique, in paraffin embedded RCC samples. Protein expression has been compared to clinical and histopathological data and to disease specific survival of RCC patients, by Kaplan-Meier curve and Cox multivariate regression analyses. Two groups of RCCs were obtained by esteeming MDR-1 expression and disease specific survival (obtained with Kaplan-Meier curve and Cox multivariate regression analyses): the first one presents low or absent MDR-1 expression and good survival; the second one is characterized by high MDR-1 expression and significant poor outcome (p < 0.05). Afterwards, we have found disease specific survival, adjusted for stages and independent of therapy: this difference of survival rates was statistically significant (p < 0.05). Stage adjusted disease specific survival rate, according to MDR-1 expression and therapy in patients affected by RCC in early stage (stage I), has revealed that the group of patients with high MDR-1 expression and without adjuvant therapy showed poor survival (p < 0.05). Cox multivariate regression analysis has confirmed that, in our cohort of RCC (clear cell type) patients, the strong association between MDR-1 and worse outcome is

  1. 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

  2. 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.

  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. 血供丰富的乏脂肪肾脏错构瘤与肾透明细胞癌的CT鉴别诊断%Differentiation of CT scan diagnosis between minimal fat renal angiomyolipoma with sufficient blood supply and clear cell renal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan Guo; Qian Peng; Zhuo Wang; Mingjuan Liu; Xufeng Yang; Teng Long

    2011-01-01

    Objective: The aim of our study was to investigate the feature of minimal fat renal angiomyolipoma with sufficient blood supply using CT scans and improve the diagnosis accuracy required to differentiate it from clear cell renal carcinoma.Methods: Retrospective analysis of 24 cases of post-surgery confirmed angiomyolipoma with sufficient blood supply (total of 25 tumors) in our hospital that were used for a pathological comparison study. Results: Among the 24 patients diagnosed with angiomyolipoma, nobody had bloody urine. Of the 96 patients diagnosed with clear cell renal cancer, 14 had bloody urine (14.6%). In our studied group, the size of angiomyolipomas with sufficient blood supply was between 1.5 cm×2.0 cm to 8.0cm × 10.0 cm. During CT scan analysis, twenty tumors had similar density, and five of them had higher density. Only one tumor had a few dots of calcification (4%). Adipose tissue was not visible in 9 tumors, while 16 tumors had visible dots of adipose tissue, as visualized by CT scan. Intensive scanning indicated that all of the tumors showed a strong enhancement in the renal corticomedullary phase. Twenty tumors had significant heterogeneous enhancement in the early phase, while another set of five cases had homogenous prolonged enhancement. Nineteen patients had surgery to remove the angiomyolipomas, while six patients had single side kidney removal due to misdiagnosis for renal cancer in cases where the tumor severely compromised the renal parenchyma and sinus. All 25 cases were classified as renal angiomyolipoma by pathological analysis. Within the 96 cases of clear cell renal cancer, 64 tumors had relatively low density, 29 tumors had equal density, and 3 cases had relatively higher density. Fourteen of the tumors had calcification (14.6% ), and none of them had visualized adipose tissue.Enhanced CT scans indicated that 69 cases of renal cancer showed significant enhancement in the renal corticomedullary phase, which had the abnormal pattern of

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

    OpenAIRE

    Nilsson, Helén; Lindgren, David; Mandahl Forsberg, A; Mulder, Hindrik; Axelson, Håkan; Johansson, Martin

    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-...

  7. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S;

    2008-01-01

    to CXCR4 and its ligand CXCL12 in ccRCC is unclear. By using reverse transcription PCR, immunofluorescence and immunohistochemistry, strong mRNA and protein expression of CXCR4, CXCL12, MMP2, MMP9 and MMP inhibitors TIMP1 and TIMP2 was found in VHL-null 786-O ccRCC cells. Loss of CXCR4/CXCL12 expression......-expression of CXCR4 and MMP2 was found in 282 of these tumours (74%). Our in vitro and in vivo data strongly indicate that pVHL coordinately regulates expression of metastasis-associated genes CXCR4/CXCL12 and MMP2/MMP9 but the exact molecular mechanism of this regulation remains to be determined. Co......-expression of CXCR4 and CXCL12, as demonstrated in VHL-null 786-O cells, might enable ccRCC progression and metastatic dissemination by autocrine receptor stimulation, even in the absence of exogenous CXCL12....

  8. Methods to identify molecular expression of mTOR pathway: a rationale approach to stratify patients affected by clear cell renal cell carcinoma for more likely response to mTOR inhibitors

    Science.gov (United States)

    Fiorini, Claudia; Massari, Francesco; Pedron, Serena; Sanavio, Sara; Ciccarese, Chiara; Porcaro, Antonio Benito; Artibani, Walter; Bertoldo, Francesco; Zampini, Claudia; Sava, Teodoro; Ficial, Miriam; Caliò, Anna; Chilosi, Marco; D’Amuri, Alessandro; Sanguedolce, Francesca; Tortora, Giampaolo; Scarpa, Aldo; Delahunt, Brett; Porta, Camillo; Martignoni, Guido; Brunelli, Matteo

    2014-01-01

    Since target therapy with mTOR inhibitors plays an important role in the current management of clear cell renal cell carcinoma (RCC), there is an increasing demand for predictive biomarkers, which may help to select patients that are most likely to benefit from personalized treatment. When dealing with formalin-fixed paraffin-embedded (FFPE) cancer tissue specimens, several techniques may be used to identify potential molecular markers, yielding different outcome in terms of accuracy. We sought to investigate and compare the capability of three main techniques to detect molecules performing an active function in mTOR pathway in RCC. Immunohistochemistry (IHC), Western blot (WB) and immunofluorescence (IF) analyses were performed on FFPE RCC tissue specimens from 16 patients by using the following mTOR pathway-related: mTOR (Ser235/236), phospho-mTOR (p-mTOR/Ser2448), phospho-p70S6k (p-p70S6k/Thr389), both monoclonal and polyclonal, phospho-S6Rb (p-S6Rb) and phospho-4EBP1 (p-4EBP1/Thr37/46). No single molecule was simultaneously revealed by all three techniques. Only p-p70S6k was detected by two methods (IHC and IF) using a monoclonal antibody. The other molecules were detected exclusively by one technique, as follows: p-mTOR and polyclonal p-p70S6K by IHC, p70S6K, p-S6Rb and p-4EBP1 by WB, and, finally, mTOR by IF. We found significant differences in detecting mTOR pathway-related active biomarkers by using three common techniques such as IHC, WB and IF on RCC samples. Such results have important implications in terms of predictive biomarker testing, and need to be related to clinical end-points such as responsiveness to targeted drugs by prospective studies. PMID:25520878

  9. Dicer expression in relation to tumorigenesis and metastasis of clear cell renal cell carcinoma%Dicer表达与肾透明细胞癌发生及转移的关系

    Institute of Scientific and Technical Information of China (English)

    范阳; 黄庆波; 高宇; 艾青; 倪栋; 陈伟浩; 马鑫; 张旭

    2013-01-01

    目的:探讨Dicer在肾透明细胞癌发生及转移中的作用.方法:选取正常肾小管上皮细胞株HKC、非转移性肾透明细胞癌细胞株769-P、转移性肾透明细胞癌细胞株Caki-1以及36例肾透明细胞癌手术标本(其中11例已发生远处转移)和相应癌旁正常肾组织,应用实时定量PCR和Western blot方法检测Dicer在肾透明细胞癌细胞株和组织中mRNA和蛋白的表达情况,并分析Dicer的mRNA水平与临床病理资料的关系.结果:和正常肾小管上皮细胞株HKC相比,Dicer的mRNA水平在肾透明细胞癌细胞株769-P和Caki-1中均降低(P<0.001),而转移性肾透明细胞癌细胞株Caki-1比非转移性肾透明细胞癌细胞株769-P表达水平更低(P<0.001);和癌旁正常肾组织相比,Dicer的mRNA水平在肾透明细胞癌手术标本中明显降低(P<0.001),且已发生远处转移的肾癌标本比末发生远处转移的肾癌标本表达水平更低(P=0.01);Dicer在细胞株和组织中的蛋白水平的变化与mRNA水平的变化一致(P <0.001);Dicer的mRNA水平在不同年龄、性别、组织学分级、肿瘤大小及T分期组间无统计学差异(P>0.05).结论:Dicer表达降低可能在肾透明细胞癌的肿瘤发生中发挥作用,且其表达的进一步下降可能与肾透明细胞癌的远处转移有关.%Objective:To explore the role of Direr in tumorigenesis and metastasis of clear cell renal cell carcinoma (ccRCC). Method:The expression of Dicer in mRNA and protein levels were detected in human kidney tubule epithelial cell line HKC. non-metastatic ccRCV cell line 769-P, metastatic ccRCC cell line Caki-1 . and 36 cases of ccRCC surgical specimens( including 11 cases with distant metastasis)and their corresponding adjacent normal renal tissues by real-time PCR and Western blot respectively, analyzing the relationship between the mRNA levels of Dicer and clinicopathological variables. Result:Compared to human kidney tubule epithelial cell line

  10. 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.

  11. 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...

  12. Renal Medullary Interstitial Cells

    Science.gov (United States)

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

    2007-04-01

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

  13. microRNAs在肾透明细胞癌组织中的异常表达%Microarray Analysis of MicroRNA Expression in Renal Clear Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    彭武建; 黄远帅; 张丽; 戴勇

    2011-01-01

    Objective: To investigate the differentially expressed microRNAs and their target genes in renal clear cell carcinoma (RCCC) , which are useful for further studies on functions of microRNAs in pathogenesis of renal clear cell carcinoma (RCCC). Methods:The microRNAs expression profiles were analyzed in 11 pairs of RCCC and adjacent nontumorous tissue (NT) ,from 11 RCCC patients,using a mammalian microRNAs microarray containing whole human mature and precursor microRNAs sequences. Results: 81 microRNAs were identified valid expression in RCCC samples,48 of which only detected in RCCC samples;42 microRNAs identified valid expression in only NT samples,9 of which were found only in NT samples. In the 33 microRNAs found both in RCCC and NT samples expression levels of 19 microRNAs were analyzed significant difference. The chip results were confirmed by northern blot analysis. Conclusions:The expression profile of microRNA is changed in RCCC samples, which implies that those changed microRNAs may play an important role in the pathogenesis of RCCC.%目的:应用microRNAs芯片筛选肾透明细胞癌细胞差异表达microRNAs,并寻找差异表达microRNAs调控的靶基因,为进一步研究其在肾透明细胞癌发病机制中的作用打下基础.方法:应用哺乳动物microRNAs表达谱芯片检测11位肾透明细胞癌患者癌组织及非肿瘤肾组织中microRNAs差异表达.结果:81种microRNAs在肾透明细胞癌组中有效表达,其中48种microRNAs仅在肾透明细胞癌组中有效表达;42种microRNAs在对照组中有效表达,9种microRNAs仅在对照组中有效表达.33种microRNAs在两组中均表达、其 中19种microRNAs表达分析有显著差异.芯片显示结果经northern blot分析确认.结论:microRNAs在肾透明细胞癌细胞中异常表达,提示它们可能在肾透明细胞癌的发生发展中起着重要的调控作用.

  14. 定量动态增强MRI对肾透明细胞癌及乏脂肪肾血管平滑肌脂肪瘤的鉴别诊断价值%The value of quantitative dynamic contrast enhanced MRI in differential diagnosis of renal clear cell carcinoma and renal angiomyolipomas with minimal fat

    Institute of Scientific and Technical Information of China (English)

    苗燕平; 高阳; 曹鹏

    2015-01-01

    目的:探讨定量动态增强磁共振成像(dynamic contrast-enhanced MRI, DCE-MRI)对肾透明细胞癌、乏脂肪肾血管平滑肌脂肪瘤的鉴别能力。材料与方法收集38例经手术病理证实的肾脏肿瘤患者,其中肾透明细胞癌26例,乏脂肪肾血管平滑肌脂肪瘤12例,术前均行常规MRI、DCE-MRI扫描,选取感兴趣区测量肿瘤的动态增强定量参数Ktrans(容量转移常数)、Kep(速率常数)、Ve(血管外细胞外间隙容积比),并对得到的数据进行分析。结果经DCE-MRI检查的26例肾透明细胞癌患者中病灶区在动态增强扫描的早期强化,定量参数Ktrans、Kep、Ve均值分别为(0.625±0.313) min-1、(1.764±1.105) min-1、(-0.341±0.207);12例乏脂肪肾血管平滑肌脂肪瘤的定量参数K trans、K ep、Ve均值分别为(0.061±0.023) min-1、(0.916±0.313) min-1、(-0.146±0.074)。Ktrans在肾透明细胞癌与乏脂肪肾血管平滑肌脂肪瘤间的差异有统计学意义(t=4.063,P<0.05), Kep、Ve在肾透明细胞癌与乏脂肪肾血管平滑肌脂肪瘤间的差异无统计学意义(t值分别为2.153、0.5,P>0.05)。结论定量DCE-MRI技术对肾透明细胞癌与乏脂肪肾血管平滑肌脂肪瘤有良好的鉴别诊断作用。%AbstractObjective:To explore the differential diagnosis value of quantitative dynamic contrast-enhanced MRI(DCE-MRI) of renal clear cell carcinoma and renal angiomyolipomas with minimal fat. Materials and Methods:Twenty-six cases with renal clear cell carcinoma, twelve cases with renal angiomyolipomas with minimal fat confirmed by operation, underwent the examination of MRI conventional scanning, and DCE-MRI. ROI were drawn to record the quantitative parameters average values of Ktrans, Kep, Ve. Results were statistically treated with SPSS 13.0.Results:Twenty-six cases with renal clear cell carcinoma showed obvious enhancement in the early phase of DCE-MRI. The Ktrans, Kep, Ve average value of renal cell

  15. Oral Cavity Clear Cell Odontogenic Carcinoma.

    Science.gov (United States)

    Ginat, Daniel Thomas; Villaflor, Victoria; Cipriani, Nicole A

    2016-06-01

    A case of clear cell odontogenic carcinoma of the oral cavity is described in this sine qua non radiology-pathology correlation article. CT demonstrated a solid and cystic mass arising from the mandible. Histology demonstrated variably-sized nests of clear to pale eosinophilic cells with occasional central necrosis embedded in a hyalinized to fibrocellular stroma. The specimen was also positive for the characteristic rearrangement of the EWSR1 (22q12) locus in 93.5 % of interphase cells. PMID:25994920

  16. 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.

  17. Clear cell sarcoma of the kidney: A case report

    Directory of Open Access Journals (Sweden)

    Dipanwita Nag

    2014-01-01

    Full Text Available Clear cell sarcoma of the kidney is a rare malignant neoplasm of childhood, known for its aggressiveness, its tendency for recurrence, and to metastasize to bone. We report the observation of 8-month-old child presenting with a large abdominal mass. Clinically, it was diagnosed as Wilm′s tumor, and left nephrectomy was done. Grossly, 10 cm × 8 cm × 3.5 cm globular, white, encapsulated, smooth mass uniformly involving the whole kidney was noted. Histologically, the tumor was diagnosed as clear cell sarcoma with renal vein showing presence of tumor embolus in lumen. The tumor was given stage-II (NWTS-5 protocol. Immunohistochemistry showed vimentin positive and cytokeratin negative tumor cells. The child is currently undergoing chemotherapy and has not yet shown any sign of bony metastasis.

  18. The management of clear cell sarcoma

    NARCIS (Netherlands)

    Kuiper, DR; Hoekstra, HJ; Veth, RPH; Wobbes, T

    2003-01-01

    Clear cell sarcoma is a rare soft tissue tumour, constituting approximately 1% of all soft tissue sarcomas. Prognosis is reported to be poor due to the great propensity to metastasise regionally and distantly. In this paper, we report the surgical experience of two university hospitals. Both disease

  19. The value of 3.0 T MR in differential diagnosis of clear cell renal cell carcinoma and renal angiomyolipoma%3.0T MR对肾透明细胞癌和血管平滑肌脂肪瘤的鉴别诊断价值

    Institute of Scientific and Technical Information of China (English)

    韩文斐; 花蒨蒨; 王亮; 韩雪; 张洁; 刘庆伟

    2014-01-01

    目的 探讨结合MR平扫及增强参数、动态增强特征在肾透明细胞癌(clear cell renal cell carcinoma,CCRCC)及血管平滑肌脂肪瘤(renal angiomyolipoma,AML)鉴别诊断中的价值.方法 回顾性分析行3.0T MR平扫及增强扫描并经手术病理证实的肾透明细胞癌17例和血管平滑肌脂肪瘤12例,对压脂T2 WI(T2 WI-FS)信号、正反相位T1WI信号、强化程度进行定量测量.绘制ROC曲线,根据敏感性、特异性、Youden指数确定肿瘤与肾实质T2 WI信号强度(signal intensity,SI)比值阈值、正反相位信号强度比值百分比(SII)阈值、增强动脉-延迟期信号强度比值阈值.根据动态强化特征,绘制动态强化时间-信号曲线.结果 CCRCC的T2 WI SI比值、动脉-延迟期信号强度比值均大于AML,AML的SII大于CCRCC.CCRCC增强动脉期信号强度大于延迟期信号强度,而AML增强动脉期信号强度与延迟期信号强度相近.动态强化曲线显示为两型,一为流出型,其中CCRCC 16例,AML6例;二为平台型,其中CCRCC 1例,AML 2例.结论 在本研究中,CCRCC、AML T2 WI SI比值、SII、动脉-延迟信号强度比值有显著差异,动态增强扫描强化曲线各有不同.根据T2WI SI比值、SII、动脉-延迟信号强度比值可区分CCRCC和AML,其阈值分别为0.738、9.170%、1.224.

  20. Clear cell carcinoma of the female genital tract (not everything is as clear as it seems).

    Science.gov (United States)

    Offman, Saul L; Longacre, Teri A

    2012-09-01

    Clear cell carcinoma has a storied history in the female genital tract. From the initial designation of ovarian clear cell adenocarcinoma as "mesonephroma" to the linkage between vaginal clear cell carcinoma and diethylstilbestrol exposure in utero, gynecologic tract clear cell tumors have puzzled investigators, posed therapeutic dilemmas for oncologists, and otherwise presented major differential diagnostic challenges for pathologists. One of the most common errors in gynecologic pathology is misdiagnosis of clear cell carcinoma, on both frozen section and permanent section. Given the poor response to platinum-based chemotherapy for advanced-stage disease and increased risk of thromboembolism, accurate diagnosis of clear cell carcinoma is important in the female genital tract. This review (1) presents the clinical and pathologic features of female genital tract clear cell carcinomas; (2) highlights recent molecular developments; (3) identifies areas of potential diagnostic confusion; and (4) presents solutions for these diagnostic problems where they exist.

  1. An unusual case of clear cell meningioma

    Directory of Open Access Journals (Sweden)

    Deb Prabal

    2009-01-01

    Full Text Available Clear-cell meningioma (CCM is an uncommon, aggressive variant of meningioma, usually affecting younger females and having predilection for infratentorial locations. We present a rare case of recurrent supratentorial CCM in a 58-year-old male. Ten years back, he had an intra-axial tumor in the left occipital lobe, which was managed by surgical excision and radiotherapy. Currently, the patient presented with sudden severe headache along with speech and vision disturbances. Neuroimaging revealed an extra-axial parietooccipital tumor, with intratumoural bleed. Histopathology of both tumors showed features of CCM, immunopositive for epithelial membrane antigen (EMA and vimentin. This case illustrates multiple unusual features of a rare variant of meningioma in the form of affection of an adult age group, supratentorial location, recurrence, and intratumoral bleed. It also highlights the importance of incorporating immunohistochemistry in the diagnostic workup, to exclude CCM mimics, each having distinctive biological behavior, and prognostic outcome, and warranting different therapeutic protocols.

  2. Sunitinib for advanced renal cell cancer

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2008-03-01

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

  3. Hemostatic completion of percutaneous nephrolithotomy using electrocauterization and a clear amplatz renal sheath

    Directory of Open Access Journals (Sweden)

    Ho Song Yu

    2016-02-01

    Full Text Available ABSTRACT Background and Purpose A tubeless PCNL can reduce postoperative pain, the need for analgesics, hospital stay, and postoperative urinary leakage. However, perioperative or delayed bleeding remains the primary postoperative concern. We demonstrate a simple and cost-effective method to develop a clear nephrostomy tract after completion of a tubeless PCNL. Materials and Methods Four consecutive patients with renal calculi >3cm underwent a tubeless PCNL. We used a 24 Fr nephroscope and a 24 Fr transurethral resectoscope. Intraoperative urologist-directed percutaneous renal access was performed under fluoroscopy. After calculi removal, active bleeders were identified via a clear Amplatz renal sheath. The sheath provided excellent visualization of the nephrostomy tract for the detection of bleeders and surrounding structures. Bleeders were electrocauterized using a roller barrel electrode. During extraction of the renal sheath, the surgeon can confirm hemostasis in the tract and apply intermittent suction. Results Bleeding primarily originated from the torn calyeceal mucosa and the parenchyma. Tract electrocauterization was successful. All patients had mild hematuria, which resolved within two days. The average hemoglobin decrease was 1.65g/dL (0.8-2.1 and no patients required a transfusion. No perioperative complications occurred. On postoperative day 2, the patients could ambulate without a Foley catheter. During three months of follow-up, delayed bleeding or percutaneous urine leakage did not occur. Conclusions Electrocauterization with a roller barrel electrode and a clear Amplatz renal sheath is an effective method to obtain hemostasis after completion of a PCNL. Our technique is cost-effective and readily adapted without the need for additional instruments.

  4. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  5. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  6. [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

  7. Guidelines on renal cell cancer

    NARCIS (Netherlands)

    Mickisch, G; Carballido, J; Hellsten, S; Schuize, H; Mensink, H

    2001-01-01

    Objectives., On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and. Follow Up of Renal. Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. Method: A sy

  8. Renal dendritic cells: an update

    OpenAIRE

    Velázquez, Peter; Dustin, Michael L.; Peter J Nelson

    2009-01-01

    Discovery into the role of renal dendritic cells (rDCs) in health and disease of the kidney is rapidly accelerating. Progress in deciphering DC precursors and the heterogeneity of monocyte subsets in mice and humans are providing insights into the biology of rDCs. Recent findings have extended knowledge of the origins, anatomy, and function of the rDC network at steady-state and during periods of injury to the renal parenchyma. This brief review highlights these new findings and provides an u...

  9. Quantitative analysis of chemical shift imaging in the differentiation of renal angiomyolipoma with minimal fat from clear cell renal cell carcinoma%化学位移成像定量分析鉴别乏脂肪肾血管平滑肌脂肪瘤与肾透明细胞癌

    Institute of Scientific and Technical Information of China (English)

    孙 军; 邢 伟; 陈 杰; 陈铜兵; 曹赟杰; 邢士军; 沈 楠

    2013-01-01

    Objective To evaluate the value of quantitative analysis of chemical shift imaging(CSI) in differential diagnosis of renal angiomyolipoma (RAML) with minimal fat from renal clear cell carcinoma (RCCC) at 3. 0 T MR. Methods The CSI images of 17 cases with pathologically proved RAML with minimal fat (Group 1) and 32 cases with pathologically confirmed RCCC (Group 2) were analyzed retrospectively. Signal intensity of tumor, spleen, and erector spinac were measured on in-phase and out-phase images, respectively. Three parameters, including signal intensity index(SII), tumor to spleen ratio(TSR) and tumor to muscle ratio (TMR) were calculated. These parameters were compared between two groups by Student's it-test respectively. The ROC curves were performed to evaluate the sensitivity and specificity of these parameters in differentiation between two groups respectively. Results There were significant differences in SII, TSR and TMR between two groups respectively (t= 12. 577, -5. 297, -05. 402, P = 0. 000). The area under curve(AUC) of ROC for SII was 0. 987, and the sensitivity and specificity were 94. 1 % and 93. 7% respectively when the optimal threshold was 18. 23%. The AUC for TSR was 0. 885, and the sensitivity and specificity were 88. 2% and 81. 2% respectively when the optimal threshold was - 12. 58%. The AUC for TMR was 0. 879, and the sensitivity and specificity were 82.4% and 78. 1% respectively when the optimal threshold was- 11. 62%. Conclusion The quantitative analysis of CSI plays an important role in differential diagnosis of RAML with minimal fat from RCCC.%目的 评价3.0T磁共振化学位移成像(CSI)定量分析在乏脂肪肾血管平滑肌脂肪瘤(RAML)与肾透明细胞癌(RCCC)鉴别诊断中的价值.方法 回顾性分析经病理证实的17例乏脂肪RAML与32例RCCC的CSI图像,测量同、反相位图像上肿瘤及参照组织脾脏、竖脊肌的信号强度,计算肿瘤信号强度指数(SII)、肿瘤脾脏信号比(TSR

  10. 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

  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. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

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

    2015-01-01

    in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg......BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.)....

  13. Familial Non-VHL Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    ... syndromes. For more information, talk with an assisted reproduction specialist at a fertility clinic. How common is ... of the internal organs, computed tomography (CT or CAT) scan , which creates a three-dimensional picture of ...

  14. Screening and regulation network analysis of clear cell renal cell carcinoma related differentially expressed miRNAs%肾透明细胞癌相关特异miRNAs的筛选及分子网络调控机制分析

    Institute of Scientific and Technical Information of China (English)

    何昊玮; 葛京平; 董杰; 王林辉

    2013-01-01

    Objective Micro RNAs (miRNAs) have been identified as key regulators in many biological processes , including proliferation, cell cycle control, apoptosis escape , tissue invasion and metastasis , angiopoiesis and unlimited replication potential. This study was to analyze differentially expressed miRNAs in clear cell renal cell carcinoma ( ccRCC ) and its adjacent normal renal tissue , investigate the regulating mechanisms of their molecular networks and verify the targets of the hub -miRNAs. Methods TargetScan software was employed to predict the targets of deregulated miRNAs . The regulation network of differentially expressed miRNAs and the target genes was established using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Luciferase assay was performed to verify the targets of the hub -miRNA. Results miR-22, miR499a-5p and miR-429 were the key miRNAs in the regulation network, and TGFBR1 and JUNB were the direct targets of miR-199a-5p. Conclusion Our findings suggest an important regula — tory role of miR-199a-5p in the tumorigenesis of ccRCC by inhibiting the expressions of its targets TGFBR 1 and JUNB.%目的 miRNAs(microRNAs)是肿瘤重要的调节因子,对细胞增殖、细胞周期的控制、逃避细胞凋亡、组织侵袭及转移、血管形成、无限复制潜力均起到重要的调节作用.文中对肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)与癌旁正常肾组织的差异miRNAs表达谱进行分子网络调控机制分析,找到关键miRNA并验证其靶基因.方法 通过TargetScan预测得到差异miRNA调控的所有靶基因,并在筛选后利用GO显著性功能分析和KEGG Pathway显著性分析,构建差异miRNA与靶基因的调控网络.筛选关键miRNA及其靶基因,对miR-199a-5p调控的靶基因进行验证.结果 miR-22、miR-199a-5p、miR-429是调控网络的关键miRNA.转化生长因子β受体1(transforming growth factor-β receptor 1,TGFBR1)、jun B原癌基因(jun B

  15. Identification of novel therapeutic targets in microdissected clear cell ovarian cancers.

    Directory of Open Access Journals (Sweden)

    Michael P Stany

    Full Text Available Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. All the arrays were analyzed using BRB ArrayTools and PathwayStudio software to identify the signaling pathways. Identified pathways validated using serous, clear cell cancer cell lines and RNAi technology. In vivo validations carried out using an orthotopic mouse model and liposomal encapsulated siRNA. Patient-derived clear cell and serous ovarian tumors were grafted under the renal capsule of NOD-SCID mice to evaluate the therapeutic potential of the identified pathway. We identified major activated pathways in clear cells involving in hypoxic cell growth, angiogenesis, and glucose metabolism not seen in other histotypes. Knockdown of key genes in these pathways sensitized clear cell ovarian cancer cell lines to hypoxia/glucose deprivation. In vivo experiments using patient derived tumors demonstrate that clear cell tumors are exquisitely sensitive to antiangiogenesis therapy (i.e. sunitinib compared with serous tumors. We generated a histotype specific, gene signature associated with clear cell ovarian cancer which identifies important activated pathways critical for their clinicopathologic characteristics. These results provide a rational basis for a radically different treatment for ovarian clear cell patients.

  16. 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...

  17. Evaluating hemorrhage in renal cell carcinoma using susceptibility weighted imaging.

    Directory of Open Access Journals (Sweden)

    Wei Xing

    Full Text Available BACKGROUND: Intratumoral hemorrhage is a frequent occurrence in renal cell carcinoma and is an indicator of tumor subtype. We hypothesize that susceptibility weighted imaging (SWI is sensitive to hemorrhage in renal cell carcinoma and can give a more diagnostic image when compared to conventional imaging techniques. MATERIALS AND METHODS: A retrospective review of 32 patients with clear cell renal cell carcinoma was evaluated. All patients underwent magnetic resonance imaging (MRI and 22 out of 32 patients also underwent a computed tomography (CT scan. Hemorrhage was classified into 3 different categories according to shape and distribution. Histopathology was obtained from all masses by radical nephrectomy. The ability to detect the presence of hemorrhage using CT, non-contrast conventional MRI and SWI was evaluated, and the patterns of hemorrhage were compared. RESULTS: Using pathologic results as the gold standard, the sensitivities of non-contrast conventional MRI, SWI and CT in detecting hemorrhage in clear cell renal cell carcinoma were 65.6%, 100% and 22.7%, respectively. Accuracy of non-contrast conventional MRI and SWI in evaluating hemorrhagic patterns were 31.3% and 100%, respectively. CONCLUSION: These results demonstrate that SWI can better reveal hemorrhage and characterize the pattern more accurately than either non-contrast conventional MRI or CT. This suggests that SWI is the technique of choice for detecting hemorrhagic lesions in patients with renal cancer.

  18. Aldesleukin in advanced renal cell carcinoma.

    Science.gov (United States)

    Schmidinger, Manuela; Hejna, Michael; Zielinski, Christoph C

    2004-12-01

    Renal cell carcinoma accounts for 2-3% of all malignancies. The most common subtype [85%] is the clear cell variant. A total of 30% of patients present with metastatic disease at diagnosis and another 30-40% will develop metastases during the course of the disease. Conventional cancer treatment is not effective, but cytokines including recombinant interleukin-2 (aldesleukin) have demonstrated clinical activity of various degrees. This drug profile provides a review of the literature on studies using aldesleukin in patients with metastatic renal cell carcinoma. Aldesleukin has been used in different dose schedules applying various administration routes, as either monotherapy or in combination with other cytokines, chemotherapy, endocrine treatment and adoptive cellular immunotherapy. Although a large number of randomized trials have been performed with different treatment strategies, it still remains uncertain whether the dose or combination of aldesleukin with other agents substantially influence treatment outcome. It appears that factors other than those that are treatment related are responsible for the course of the disease. PMID:15606326

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  20. The Heidelberg classification of renal cell tumours

    NARCIS (Netherlands)

    Kovacs, G; Akhtar, M; Beckwith, BJ; Bugert, P; Cooper, CS; Delahunt, B; Eble, JN; Fleming, S; Ljungberg, B; Medeiros, LJ; Moch, H; Reuter, VE; Ritz, E; Roos, G; Schmidt, D; Srigley, [No Value; Storkel, S; VandenBerg, E; Zbar, B

    1997-01-01

    This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996, The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic t

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

    Directory of Open Access Journals (Sweden)

    Rombo, Roman

    2016-04-01

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

  2. Molecular Characterization of Clear Cell Lesions of Head and Neck.

    Science.gov (United States)

    Jain, Anshi; Shetty, Devi Charan; Juneja, Saurabh; Narwal, Nidhi

    2016-05-01

    The salivary glands, oral mucosa and jaws constitute a group of lesions which are heterogeneous in nature and are odontogenic, salivary or metastatic in origin. This group of tumours is termed as Clear Cell Tumours. Fixation artifacts are one of the most important reasons for the cell to appear clear but clearing of cells may also result from cytoplasmic accumulation of water, presence of glycogen within the cell, intermediate filaments, immature zymogen granules, or a paucity of cellular organelles. Clear cell Odontogenic neoplasms predominantly include odontogenic carcinoma, ameloblastoma and calcifying epithelial odontogenic tumour. Clear cell tumours of salivary gland origin are almost invariably malignant in nature but they do include two benign lesions. Very frequently, surgical pathologist encounters clear cells in many malignant neoplasms, the nature and sources of which are undetermined on the basis of conventional histopathology. This review will selectively discuss the clinicopathological features of neoplasms which at times may pose a diagnostic challenge and dilemma due to clear cell changes. PMID:27437379

  3. 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

  4. 肾透明细胞癌组织肾母细胞瘤过表达基因表达临床意义的探讨%Expression of NOV and its clinical significance in clear cell renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    牛志宏; 毕东滨; 吕家驹

    2012-01-01

    OBJECTIVE:To investigate the relationship between the expression of NOV and the stage,grade,proliferation index and prognosis of clear cell renal cell carcinoma(RCC). METHODS: Fifty-four samples of clear cell RCC tissues were collected. NOV expression and Ki-67 index were examined by immunohistochemical staining. RESULTS: The immunostaining intensity of NOV was significantly lower in tumor compared to normal kidney tissue and strong NOV expressions were demonstrated in all 22 normal kidney tissues. In contrast only 24(44. 4%) tumors were found to be weakly positive and 8(14. 8%) tumors were found to be moderately positive. The positive rate of NOV was also lower in tumor (59. 3%) compared to normal kidney tissue(100%). The Ki-67 index was significantly higher in NOV negative tumor [(4. 2 ± 2. 1)%] than that in NOV positive tumor [(2. 6±1. 5)%,P<0. 053. NOV expression could not be correlated with stage,grade,and size of tumors. The NOV positive group showed significantly higher 5 year cancer specific survival rate compared to NOV negative group (82. 6% vs 50. 3% ,P<0. 05). CONCLUSION; The results of this study suggest that NOV could play inhibitory role in clear cell RCC.%目的:探讨肾母细胞瘤过表达基因(NOV)对肾透明细胞癌分级、分期、大小、增殖状态和预后的影响.方法:应用免疫组化法检测54例肾透明细胞癌组织NOV蛋白的表达,分析其与肾透明细胞癌分期、分级、大小、Ki-67指数的相关性,并比较NOV阳性组和阴性组的生存率差异.结果:NOV在肾脏透明细胞癌组织中的染色强度明显低于癌旁正常肾组织,22例(100%)癌旁正常肾组织均呈强阳性染色,54例肾癌组织中24例(44.4%)为弱阳性染色,8例(14.8%)为中等阳性染色 ;癌组织总阳性率(59.3%)亦显著低于癌旁正常肾组织(100%),P<0.05.NOV阳性组的Ki-67指数(2.6±1.5)%,明显低于NOV阴性组的(4.2±2.1)%,P<0.05.NOV表达与肿瘤分期及大小无相关性,P>0

  5. Inactivation of the von Hippel-Lindau tumour suppressor gene induces Neuromedin U expression in renal cancer cells

    OpenAIRE

    Shukla Deepa; Esteban Miguel A; Harten Sarah K; Ashcroft Margaret; Maxwell Patrick H

    2011-01-01

    Abstract Background 209 000 new cases of renal carcinoma are diagnosed each year worldwide and new therapeutic targets are urgently required. The great majority of clear cell renal cancer involves inactivation of VHL, which acts as a gatekeeper tumour suppressor gene in renal epithelial cells. However how VHL exerts its tumour suppressor function remains unclear. A gene expression microarray comparing RCC10 renal cancer cells expressing either VHL or an empty vector was used to identify novel...

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

    Science.gov (United States)

    Nosnik, Israel P; Mouraviev, Vladimir; Nelson, Rendon; Polascik, Thomas J

    2006-12-01

    Patients with metachronous bilateral renal cell carcinoma pose a significant challenge given the high mortality of renal cell carcinoma and the poor quality of life should dialysis become necessary. In addition, patients may be subject to morbidity due to potential multiple treatments of the multifocal renal tumors. We present the case of a 71-year-old woman with multifocal, bilateral clear cell carcinoma who maintained a minimal change in serum creatinine after undergoing unilateral radical nephrectomy, subsequent percutaneous radiofrequency ablation, percutaneous cryoablation, laparoscopic cryoablation, and open partial nephrectomy for recurrent renal cell carcinoma in a solitary kidney.

  7. 组氨酸三聚体核苷结合蛋白1在肾透明细胞癌中的表达及意义%Expression of histidine triad nucleotide-binding protein 1 in clear cell renal cell carcinoma and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    杨斌; 邢金春; 李伟; 张开颜; 吴准; 陈志阳; 杨盛华

    2011-01-01

    Objective: To determine the expressions of histidine triad nucleotide-binding protein 1 (HINT1) mRNA and protein in clear cell renal cell carcinoma (ccRCC) and their relationships with clinicopatholgical features. Methods: Real-time fluorescence quantitative reverse transcription PCR (RFQ-RT-PCR) was used to detect the expressions of HINT1 mRNA in 36 cases of fresh ccRCC and 37 cases of normal kidney tissues (29 paired cases), as well as their relationships with clinicopathological features were analyzed. Immunohistochemistry was used to detect the distribution and expression of HINT1 protein in 30 cases of paraffin embedded fresh ccRCC tissues and 12 cases of paraffin-embedded adjacent normal kidney tissues, as well as their relationships with clinicopathological features were analyzed. Results: The expression levels of HINT1 mRNA in 29 cases of paired ccRCC and normal kidney tissues were 0.209±0.033 and 0.733±0.136, respectively (P<0.001). The expression levels of HINT1 mRNA in 36 cases of ccRCC and 37 cases of normal kidney tissues were 0.245±0.035 and 0.694± 0.108, respectively (P<0.001). The positive expression rate of HINT1 protein in the adjacent normal kidney tissues was 100% (12/12), diffusely distributing in the nucleus and cytoplasm. HINT1 protein immunostaining in proximal convoluted tubule was stronger than that in distal convoluted tubule, while it was partially weaker in glomerular basement membrane and Bowman's capsule. The HINT1 protein expression was negative in renal interstitium. HINT1 protein expression distributing in nucleus and cytoplasm was 60% (18/30) positive in ccRCC, while it was negative in intercellular substance (P<0.01). The tendency of HINT1 mRNA expression in ccRCC and normal kidney tissues and their relationships with the clinicopathological features were the same as those of HINT1 protein. The expressions of HINT1 mRNA and protein in stages T1-2 of ccRCC were higher than those in stages T3-4 (P<0.05), and the

  8. 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.

  9. Glycogen-rich clear cell carcinoma of the breast

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Paulsen, S M

    1987-01-01

    cells were stained by antisera to carcinoembryonic antigen, keratin and epithelial membrane antigen, but not by antisera to alpha-lactalbumin, desmin or vimentin. Ultrastructurally, the epithelial derivation of the tumour was confirmed. Only a few intracytoplasmic lumina were demonstrated. The tumour......The light microscopic, immunohistochemical and ultrastructural features of a clear cell carcinoma of the breast have been studied. Both intraductal and invasive components were found. Histochemistry showed large amounts of intracytoplasmic glycogen and sparse neutral mucin in the tumour. The tumour...... was classified as a mucin-containing variant of glycogen-rich, clear cell carcinoma of the breast....

  10. 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.)

  11. Isolated pleural metastases from renal cell carcionoma

    DEFF Research Database (Denmark)

    Eckardt, Jens; Ladegaard, Lars; Licht, Peter Bjorn

    2011-01-01

    A 71-year-old female was referred with three right-sided intrathoracic tumours. In 2003, she underwent radical left nephrectomy for renal cell cancer (RCC) clinical stage 1. She was since followed at her local hospital with annual computed tomography (CT)-scans during the first five years and did....... Histology demonstrated metastases from RCC which apparently can reach the parietal pleura without lung metastases. Keywords: Pleural metastasis; Renal cell cancer....

  12. 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

  13. Mesenchymal stromal cells in renal ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Dorottya K. De Vries

    2012-07-01

    Full Text Available Ischemia/reperfusion (I/R injury is an inevitable consequence of organ transplantation and a major determinant of patient and graft survival in kidney transplantation. Renal I/R injury can lead to fibrosis and graft failure. Although the exact sequence of events in the pathophysiology of I/R injury remains unknown, the role of inflammation has become increasingly clear. In this perspective, mesenchymal stromal cells (MSCs are under extensive investigation as potential therapy for I/R injury, since MSCs are able to exert immune regulatory and reparative effects. Various preclinical studies indicate the beneficial effects of MSCs in ameliorating renal injury and accelerating tissue repair. These versatile cells have been shown to migrate to sites of injury and to enhance repair by paracrine mechanisms instead of by differentiating and replacing the injured cells. The first phase I studies of MSCs in human renal I/R injury and kidney transplantation have been started, and results are awaited soon. In this review, preliminary results and opportunities of MSCs in human renal I/R injury are summarized. We might be heading towards a cell-based paradigm shift in the treatment of renal I/R injury.

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

    Directory of Open Access Journals (Sweden)

    César Pablo Ramírez-Plaza

    2015-01-01

    Conclusion: The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of “de novo” thyroid nodules in oncologic patients must be always considered and studied.

  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. Emerging surgical treatments for renal cell carcinoma.

    Science.gov (United States)

    Husain, Fatima Z; Badani, Ketan K; Sfakianos, John P; Mehrazin, Reza

    2016-04-01

    Treatment of renal cell carcinoma has evolved considerably over the last few years. While total nephrectomy is necessary at times, nephron-sparing surgery, with a goal of renal function preservation, should always be considered. Although open partial nephrectomy is considered the gold standard approach for nephron-sparing surgery, laparoscopic- or robotic-assisted techniques allow urologists to perform renal surgery less invasively, with excellent long-term oncological outcomes. Cryotherapy and radiofrequency ablation are less invasive management approaches for carefully selected patients with small renal masses. Active surveillance should be considered in elderly or patients who are unfit for surgery. Ultimately, the method chosen for management of a renal mass is an informed decision made by the physician and patient. PMID:26892144

  17. Percutaneous Cryoablation for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  18. Napsin A is a specific marker for ovarian clear cell adenocarcinoma.

    Science.gov (United States)

    Yamashita, Yoriko; Nagasaka, Tetsuro; Naiki-Ito, Aya; Sato, Shinya; Suzuki, Shugo; Toyokuni, Shinya; Ito, Masafumi; Takahashi, Satoru

    2015-01-01

    Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors. PMID:24721826

  19. Combined Papillated Bowen Disease and Clear Cell Atypical Fibroxanthoma

    Directory of Open Access Journals (Sweden)

    Dimas Suárez-Vilela

    2010-05-01

    Full Text Available We describe a case of papillated Bowen disease (PBD, associated with a clear cell atypical fibroxanthoma (CCAFXA. The epidermal lesion showed a bowenoid papillomatous growth pattern with histologic features suggestive of infection by human papilloma virus (HPV. In the dermis a neoplasm made up by spindled or polygonal cells with wide clear cytoplasm and moderate nuclear pleomorphism was found. Immunohistochemical characteristics of these two lesions were clearly different. The atypical cells of the intraepidermal proliferation were positive for AE1-AE3 anticytokeratin antibody, EMA, p16, p53 and p63. The dermal tumor was positive for vimentin, CD10, CD68, CD99, alpha-1-antitrypsin and c-kit. Histological features and immunohistochemical profile of the dermal tumor corresponded to a CCAFXA, a very uncommon neoplasm of which only 10 cases have been reported. In situ hybridization for numerous types of HPVs was negative in both lesions.

  20. Clear cell colitis: A form of microscopic colitis in children

    Institute of Scientific and Technical Information of China (English)

    Jan J(o)zefczuk; Bogdan Marian Wozniewicz

    2008-01-01

    AIM: To describe a new clinical and pathological subtype of microscopic colitis in children.METHODS: A selected group of children with abdominal pain, constipation and/or diarrhoea showing discrete or no macroscopic abnormalities on endoscopy was described.RESULTS: Multiple biopsies of colon showed large mononuclear clear cells in lamina propria of mucous membrane provided that good quality histological sections were performed and observed under a higher magnification. Otherwise, they could be misinterpreted as artefacts. Their presence in routine histology might suggest a systemic storage disease (Whipple's disease), and neuronal intestine dysplasia.Using immunohistochemical staining and electron microscopy we confirmed their origin from CD68 positive mononuclear macrophages.CONCLUSION: The presence of large clear cells is a constant microscopic feature. Failure of transient large bowel stationary macrophages plays a role in the pathogenesis of this benign microscopic clear cell colitis,sometimes coexisting with allergy.

  1. Treatment results and prognostic factors of clear cell ovarian carcinomas and ovarian carcinomas with clear cell component

    Directory of Open Access Journals (Sweden)

    M. D. Ahmedova

    2012-01-01

    Full Text Available The most important prognostic factors for clear cell carcinoma (CCC are clinical and morphological signs and clinical stage of the disease. Analyses of 5-year survival in patients with I stage of CCC is 69 %, in II stage – 55 %, in III stage – 14 % and in IV stage – 4 % patients. We analyzed distant results of treatment of 71 patients with CCC and of 25 patients with mixed malignant ovaries neoplasm with obligatory clear cell component taking into consideration main clinical and morphological sings of disease. On the base of performed reseal we revealed that morphological structure of the tumors and stage of the disease exerted heist influence on the exponent of survival of the patients with clear CCC ovaries neoplasm. Besides, there is a correlation between exponent of patients’ survival and radicalized of surgery, character of tumor growth, differentiation degree, cell anaplasia and mitotic activity of tumor cells.

  2. Clear cell adenocarcinoma of the bladder with intravesical cervical invasion.

    Science.gov (United States)

    Marchalik, Daniel; Krishnan, Jayashree; Verghese, Mohan; Venkatesan, Krishnan

    2015-01-01

    A 26-year-old woman with a complicated urological and gynecological history with uterine didelphys with bilaterally inserting intravesical cervical oses presented with cyclical haematuria. Work up revealed a mass in the ectopic cervical os and adjacent bladder wall. Subsequent resection confirmed a clear cell adenocarcinoma of urological origin with invasion into neighbouring os. PMID:26109625

  3. Clear Cell Chondrosarcoma in Association With Niemann-Pick Disease

    Directory of Open Access Journals (Sweden)

    K. N. Srikanth

    2005-01-01

    Full Text Available Purpose: The purpose of this case report is to bring to light this unusual combination of two rare diseases, namely Neimann-Pick disease Type B and clear cell chondrosarcoma occurring in the same patient. This has not previously been reported in the world literature.

  4. Clear cell variant of syringoma as a rare case

    Directory of Open Access Journals (Sweden)

    Özben Yalçın

    2014-12-01

    Full Text Available Syringoma is a benign skin tumor derived from eccrine glands characterized by yellowish-pink color and firm papular lesions of the skin especially on the lower eyelid. Typical histopathological features of syringoma are dilated cystic eccrine sweat gland ducts. In this paper, we report a case of clear cell variant syringoma with neck and trunk lesions.

  5. Clear cell ovarian cancer and endometriosis: is there a relationship?

    Science.gov (United States)

    Suzin, Jacek; Obirek, Katarzyna; Sochacka, Amanda; Łoszakiewicz, Marta

    2016-01-01

    Introduction Ovarian clear cell carcinoma is a rare type of ovarian cancer. In recent years, issues of the common genetic origin of endometriosis and ovarian clear cell carcinoma have been raised. Aim of this study Aim of this study was to evaluate the prevalence of this type of cancer, risk factors, prognosis and its potential aetiological association with endometriosis. Material and methods In a retrospective study, we analysed histopathological data of patients operated in the First Department of Gynaecology and Obstetrics (MU, Lodz) due to ovarian cancer in 2004-2014. Among the 394 patients operated on for ovarian cancer, clear cell carcinoma was found in 0.02% (9/394). Menstrual history, parity, comorbidities, data from physical examination, operational protocols and histopathological diagnoses were analysed. Follow-up was obtained from 77.8% of patients. Statistical analysis was performed using Microsoft Excel 2013. Results The mean age of patients at diagnosis was 57.6 years; the BMI in the study group was 27.2; the majority of patients were multiparous (77.8%). Clear cell carcinoma was detected mostly at stage Ia (n = 4). The concentration of Ca125 in the study group had an average of 142.75 U/ml and a median of 69.3 U/ml. The coexistence of endometriosis could not be clinically or histologically confirmed amongst our patients. The most common comorbidity in the study group was hypertension. Conclusions In our clinical material, ovarian clear cell carcinoma is a rare histopathological specimen with a prognostic value comparable to that of serous ovarian cancer. Due to the rarity of this histopathological subtype, proving a cause-and-effect relationship between it and endometriosis can only be elucidated through statistical studies of the entire population.

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

    Science.gov (United States)

    Xiao, Jiantao; Lei, Jun; He, Leye; Yin, Guangming

    2015-01-01

    Longstanding renal calculus is a risk factor of squamous cell carcinoma (SCC) of the renal pelvis. It is highly aggressive and usually diagnosed at advanced stages with a poor prognosis. We present two cases of kidney stone complications with renal pelvic SCC. These two patients had a radical nephrectomy and the dissected tissues were renal pelvic SCC. Our cases further emphasize that renal pelvic SCC should be considered in patients with longstanding renal calculus. These cases contribute greatly to an early diagnosis and early treatment, both of which will significantly minimize the damage of, and markedly improve the prognosis of, renal pelvic SCC.

  7. {sup 11}C-Acetate PET imaging for renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Kusukawa, Naoya; Kaneda, Taisei; Miwa, Yoshiji; Akino, Hironobu; Yokoyama, Osamu [University of Fukui, Department of Urology, Fukui (Japan); Okazawa, Hidehiko; Fujibayashi, Yasuhisa [University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Yonekura, Yoshiharu [National Institute of Radiological Sciences, Chiba (Japan); Welch, Michael J. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, Saint Louis, MO (United States)

    2009-03-15

    In this study, we investigated the effectiveness of positron emission tomography (PET) with {sup 11}C-acetate (AC) for evaluation of renal cell carcinoma. Enrolled in the study were 20 patients with suspected renal tumour, one of whom had three renal lesions. In all, 22 renal lesions were evaluated. Following administration of 350 MBq (10 mCi) of AC, whole-body PET images were obtained. Based on these PET findings, kidney lesions were scored as positive or negative. The PET results were correlated with the CT findings and histological diagnosis after surgery. In 18 patients, 20 tumours were diagnosed as renal cell carcinoma. Lesions in the remaining two patients were diagnosed as complicated cyst without malignant tissue. Of the 20 renal cell carcinomas. 14 (70%) showed positive AC PET findings; 6 were negative. The two patients with complicated cyst had negative AC PET findings. Of the 20 renal cell carcinomas, 19 were clear-cell carcinoma and 1 was a papillary cell carcinoma. This papillary cell carcinoma showed high AC uptake. AC demonstrates marked uptake in renal cell carcinoma. These preliminary data show that AC is a possible PET tracer for detection of renal cancer. (orig.)

  8. Renal stem cells: fact or science fiction?

    Science.gov (United States)

    McCampbell, Kristen K; Wingert, Rebecca A

    2012-06-01

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

  9. Clear Cell Chondrosarcoma in Association With Niemann-Pick Disease

    OpenAIRE

    Sumathi, V. P.; Grimer, R. J.; Davies, A. M.; Kulkarni, A.; Srikanth, K. N.

    2005-01-01

    Purpose: The purpose of this case report is to bring to light this unusual combination of two rare diseases, namely Neimann-Pick disease Type B and clear cell chondrosarcoma occurring in the same patient. This has not previously been reported in the world literature. Subject: Niemann-Pick disease (NPD) is a rare autosomal recessive inborn error of metabolism. Type B NPD is even rarer. It is a lysosomal storage disorder affecting children and adolescents often causing death in early childhood,...

  10. Cerebellar clear cell ependymoma in a 10 year old girl

    Energy Technology Data Exchange (ETDEWEB)

    Thinzar Aye Nyein; Moon, Ah Rim; Hwang, Sun Chul; Hong, Hyun Sook; Lee, A Leum; Chang, Kee Hyun; Kim, Hee Kyung; Chin, Su Sie [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Park, Ji Sang [Soonchunhyang University Gumi Hospital, Gumi (Korea, Republic of)

    2016-01-15

    Clear cell ependymoma (CCE) is a histological rare variant (1–5%) of ependymoma, which is distinguished from other histological subtypes by the presence of fusiform cells arrayed radially around small blood vessels. These alleged perivascular pseudorosettes are significant characteristic features of ependymomas. About 95% of infratentorial ependymomas are found in the fourth ventricle and the remainder occurs as cerebellopontine angle lesions. In previous reports, the cerebellum is found to be a rare location for ependymoma. In this study we report one case of CCE originating from the cerebellar hemisphere, showing unusual morphology on 3T MRI.

  11. Diabetes treatment in patients with renal disease: Is the landscape clear enough?

    Institute of Scientific and Technical Information of China (English)

    Ioannis; Ioannidis

    2014-01-01

    Diabetes is the most important risk factors for chronic kidney disease(CKD). The risk of CKD attributable to diabetes continues to rise worldwide. Diabetic patients with CKD need complicated treatment for their metabolic disorders as well as for related comorbidities. They have to treat, often intensively, hypertension, dyslipidaemia, bone disease, anaemia, and frequently established cardiovascular disease. The treatment of hypoglycaemia in diabetic persons with CKD must tie their individual goals of glycaemia(usually less tight glycaemic control) and knowledge on the pharmacokinetics and pharmacodynamics of drugs available to a person with kidney disease. The problem is complicated from the fact that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. This results in fear of use by lack of evidence. Metformin is globally accepted as the first choice in practically all therapeutic algorithms for diabetic subjects. The advantages of metformin are low risk of hypoglycaemia, modest weight loss, effectiveness and low cost. Data of UKPDS indicate that treatment based on metformin results in less total as well cardiovascular mortality. Metformin remains the drug of choice for patients with diabetes and CKD provided that their estimate Glomerular Filtration Rate(eGFR) remains above 30 mL/min per square meter. For diabetic patients with eGFR between 30-60 mL/min per square meter more frequent monitoring of renal function and dose reduction of metformin is needed. The use of sulfonylureas, glinides and insulin carry a higher risk of hypoglycemia in these patients and must be very careful. Lower doses and slower titration of the dose is needed. Is better to avoid sulfonylureas with active hepatic metabolites, which are renally excreted. Very useful drugs for this group of patients emerge dipeptidyl peptidase 4 inhibitors. These drugs do not cause hypoglycemia and most of them(linagliptin is an exception

  12. A giant benign clear cell hidradenoma on the anterior trunk

    Directory of Open Access Journals (Sweden)

    Damlanur Sakiz

    2011-10-01

    Full Text Available Clear cell hidroadenoma (CCA is a uncommon variant of bening cutaneous adnexial tumors. These tumors are clinically asymptomatic, solitary dermal nodules. they occur most frequently on the scalp, face, abdomen and the extremities. Growth is slow and malignant change is rare. 45- year-old woman presented us with a nodule with a central ulceration and a minimal hemoragic discharge on her anterior abdomen wall which had begun 4 years ago as a small nodular asymptomatic lesion. On dermatological examination there was a 6.5x4x5 cm non-tender, soft reddish purple nodule with lobular appearence and ulceration. In the laboratory investigations, all the hematologic and biochemical tests were normal. A CT scan demonstrated a cyctic tumor with lobulated countour with contrast enhancement. The lesion excised totally. In histopathological examination the tumor was composed of biphasic  smaller dark polygonal cells and larger clera cells and coarse nuclear chromatine. There were duct like structures. Immunohistochemical investigation was done for the suspicion of malignancy. Cytoplasm of clear cells and duct like structures showed PAS positive and d-Pas resistant staining. There was a positive reactivity to epithelial membrane antigen and carcinoembrionic antigen. The mitotic index in Ki 67 examination was low. All these findings confirmed the diagnosis of bening CCA. 

  13. Clear cell change in a lower lip mucocele.

    Science.gov (United States)

    Piña, Alicia Rumayor; Almeida, Luciana Yamamoto; Andrade, Bruno Augusto Benevenuto; León, Jorge Esquiche

    2013-05-01

    Oral mucocele is a common reactive lesion of the oral mucosa, which microscopically exhibits mucus extravasation surrounded by a wall of granulation tissue containing abundant foamy macrophages. Unusual variants, such as superficial mucoceles, mucoceles with myxoglobulosis-like change and mucoceles with synovial metaplasia-like change have been reported. We report a 74-year-old man who presented an asymptomatic translucent swelling on the lower labial mucosa diagnosed as mucocele showing a macrophage proliferation with extensive clear cytoplasmic vacuolation and signet-ring formation. This unusual presentation expands the microscopic spectrum of the oral mucoceles and can eventually lead to differential diagnosis with primary or metastatic clear cell neoplasms. In these cases, relevant clinical information, histochemistry and especially immunohistochemistry, are helpful for arriving at an accurate diagnosis. PMID:24250103

  14. Clear cell change in a lower lip mucocele

    Directory of Open Access Journals (Sweden)

    Alicia Rumayor Piña

    2013-01-01

    Full Text Available Oral mucocele is a common reactive lesion of the oral mucosa, which microscopically exhibits mucus extravasation surrounded by a wall of granulation tissue containing abundant foamy macrophages. Unusual variants, such as superficial mucoceles, mucoceles with myxoglobulosis-like change and mucoceles with synovial metaplasia-like change have been reported. We report a 74-year-old man who presented an asymptomatic translucent swelling on the lower labial mucosa diagnosed as mucocele showing a macrophage proliferation with extensive clear cytoplasmic vacuolation and signet-ring formation. This unusual presentation expands the microscopic spectrum of the oral mucoceles and can eventually lead to differential diagnosis with primary or metastatic clear cell neoplasms. In these cases, relevant clinical information, histochemistry and especially immunohistochemistry, are helpful for arriving at an accurate diagnosis.

  15. 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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Nevins

    2013-01-01

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

  18. Progressive renal failure due to renal infiltration by BK polyomavirus and leukaemic cells: which is the culprit?

    Science.gov (United States)

    Sangala, Nicholas; Dewdney, Alex; Marley, Nicholas; Cranfield, Tanya; Venkat-Raman, Gopalakrishnan

    2011-02-01

    Renal infiltration with leukaemic cells is a common finding in patients suffering with chronic lymphocytic leukaemia (CLL) but rarely does it lead to significant renal dysfunction. Similarly, BK nephropathy is a recognized cause of graft failure in renal transplant recipients but rarely causes significant disease in native kidneys. In the few reports where leukaemic infiltration of the kidney has led to significant renal impairment, the pathological process causing renal dysfunction is not identified on biopsy. In these cases, it is unclear whether BK polyomavirus (BKV) nephropathy has been excluded. We describe a case of dual pathologies in a patient with Binet stage C CLL and deteriorating renal function where renal biopsy reveals leukaemic infiltration of the kidney occurring alongside BKV nephropathy. The relative importance of each pathology in relation to the rapid decline to end-stage renal failure remains unclear, but the presence of both pathologies appears to impart a poor prognosis. Additionally, we describe the novel histological finding of loss of tubular integrity resulting in tubular infiltration and occlusion by leukaemic cells. It is possible that the patient with advanced CLL is at particular risk of BK activation, and the presence of BK nephropathy may compromise tubular integrity allowing leukaemic cell infiltration and obstruction of tubules. This case bares remarkable resemblance to the first and only other report of its kind in the literature. It is not clear how available immunocytochemistry for polyoma infection is outside transplant centres, and it is possible that BK nephropathy is being under-diagnosed in patients with CLL in the context of declining renal function. At present, the combination of BKV nephropathy and leukaemic infiltration represents a management conundrum and the prognosis is poor. Further research is required in order to better understand the pathological process and therefore develop management strategies.

  19. 血管内皮生长抑制因子在散发性肾透明细胞癌细胞中的表达及意义%Expression and role of vascular endothelial growth inhibitor in sporadic clear cell renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴栗洋; 程浩; 邓小虎; 善辉; 王伟; 杨勇; 张小东; 张宁

    2013-01-01

    Objective To evaluate the expression of vascular endothelial growth inhibitor (VEGI) in sporadic clear cell renal cell carcinoma (CCRCC) and explore its relationships between VEGI expression,pathologic grade and tumor staging.Methods Western blot and immunohistochemical staining were used to detect the expression of VEGI in CCRCC cell line (786-O cells),CCRCC and paired normal kidney tissues.A total of 50 CCRCC cases were recruited.There were 37 males and 13 females with an average age of 53 ±12 years.The tumor sizes were <7 cm (n=33) and ≥7 cm (n =17).Their pathologic grades were G1 (n=14),G2 (n=22) and G3 (n=14) and pathologic stages pT1 (n=32),10 pT2 (n=10) and pT3 (n =8).Results VEGI protein was predominantly located in cytoplasm.Compared with normal kidney tissues(mean optic density (MOD) of VEGI staining:0.40 ± 0.16),it was lower in CCRCC tissues (MOD:0.11 ± 0.06,P < 0.01).In addition,the positive rate of VEGI expression,the expression intensity and the MOD of VEGI protein were negatively correlated with the pathologic grade of CCRCC (r =-0.640,P <0.01 ; r =-0.831,P < 0.01 ; r =-0.781,P < 0.01 respectively).The MOD of VEGI expression in ≥7 cm tumors (MOD,0.08 ±0.04) was significantly lower than that in <7 cm tumors (MOD:0.12 ±0.06,P < 0.05).However,there was no correlations between the VEGI protein level and age,gender and pathologic stage of patients (P > 0.05).Conclusion VEGI protein is predominantly located in cytoplasm.Compared with CCRCC tissues,VEGI protein level is higher in normal ones.In consideration of negative correlations between VEGI expression,pathologic grade and tumor size,it is implied that VEGI may play a negative regulatory role in the occurrence and development of CCRCC.%目的 了解血管内皮生长抑制因子(VEGI)在散发性肾透明细胞癌(CCRCC)中的表达情况,分析其与CCRCC病理分级和分期等的关系.方法 应用Western印迹及免疫组化技术分析肾透明细胞癌细胞(786-O细胞)

  20. Continuous production of erythropoietin by an established human renal carcinoma cell line: development of the cell line

    Energy Technology Data Exchange (ETDEWEB)

    Sherwood, J.B.; Shouval, D.

    1986-01-01

    Establishment of a stable, transformed human renal carcinoma cell line that produces erythropoietin in vitro and has maintained this function continuously since 1981 and for > 150 passages in monolayer culture was accomplished by transplantation of human renal clear cell carcinoma tissue from a patient with erythrocytosis into an immunosuppressed athymic mouse. In addition to its immunocrossreactivity with native human urinary erythropoietin, the tumor erythropoietin demonstrates biological activity in the in vitro mouse erythroid colony-forming unit assay and in tumor-bearing nude mice. The cloned renal carcinoma cell line has an abnormal human karyotype and has ultrastructural features characteristic of human renal clear cell carcinoma. This cell line provides a reproducible model system for the production of an erythropoietin-like material and for the study of its synthesis and secretion.

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

    Directory of Open Access Journals (Sweden)

    Kenan Ashouri

    2015-09-01

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

  2. Renal cell carcinoma in a setting of chronic lithium toxicity

    OpenAIRE

    Zardawi, Ibrahim; Nagonkar, Santoshi; Patel, Purvish

    2013-01-01

    Patient: Female, 72 Final Diagnosis: Renal cell carcinoma Symptoms: — Medication: — Clinical Procedure: — Specialty: Oncology Objective: Challenging differential diagnosis Background: Lithium salts are widely used in the treatment of affective disorders of the bipolar type. Lithium is a nephrotoxic substance which can cause both acute and chronic renal disease, including cyst formation. Cysts appear to predispose the kidney to renal cell carcinoma. Case Report: A case of renal cell carcinoma ...

  3. Vaginal clear cell carcinoma in a Japanese Black cow.

    Science.gov (United States)

    Michishita, Masaki; Hori, Makito; Nakahira, Rei; Takahashi, Kimimasa

    2016-06-01

    During artificial insemination of an 18-year-old female Japanese Black cow, a mass that was of a hen's egg size was found in the vagina. On necropsy, the firm mass, measuring approximately 3.5 × 3.5 × 3.0 cm, was located at the superior region of the vagina. The cut surface of the mass was gray-white in color with occasional necrotic or hemorrhagic areas. Histologically, the mass was composed of tumor cells arranged in solid nests of various sizes with an occasional tubular structure separated by a delicate fibrovascular stroma. The tumor cells had a hypochromatic nucleus and abundant, faintly eosinophilic cytoplasm. The tumor cells contained diastase-sensitive periodic acid-Schiff positive granules. Immunohistochemically, tumor cells were positive for cytokeratin AE1/AE3, CAM5.2 and carcinoembryonic antigen, but not for vimentin, p63, estrogen receptor-α, progesterone receptor, α-smooth muscle actin, neuron-specific enolase, S-100 protein and chromogranin A. On the basis of these findings, the tumor was diagnosed as a clear cell carcinoma of the vagina. PMID:26852732

  4. Primary abdominal wall clear cell carcinoma arising from incisional endometriosis

    Institute of Scientific and Technical Information of China (English)

    Burcu Gundogdu; Isin Ureyen; Gunsu Kimyon; Hakan Turan; Nurettin Boran; Gokhan Tulunay; Dilek Bulbul; Taner Turan; M Faruk Kose

    2013-01-01

    A 49 year-old patient with the complaint of a mass located in the caesarean scar was admitted. There was a fixed mass 30í30 mm in diameter with regular contour located at the right corner of the pfannenstiel incision. Computed tomography revealed a (40í50í50) mm solid mass lesion with margins that cannot be distinguished from the uterus, bladder and small intestines and a heterogeneous mass lesion (50í45í55) mm in diameter, located in the right side of the anterior abdominal wall. Cytoreductive surgery including total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Final pathology was clear cell carcinoma. Clear cell carcinoma arising from an extraovarian endometriotic focus was diagnosed and the patient received 6 cycles paclitaxel-carboplatin chemotherapy as adjuvant treatment. The patient who was lost to follow-up applied to our clinic 2 years after surgery with a recurrent mass in the left inguinal region. After 3 cycles of chemotherapy, the patient's tumoral mass in the left inguinal region was excised. The result of the pathology was carcinoma metastasis. It is decided that the following treatment of the patient should be palliative radiation therapy. The patient who underwent palliative radiation therapy died of disease after 4 months of the second operation.

  5. Clear cell carcinoma arising from a uterus-like mass.

    Science.gov (United States)

    Nakakita, Baku; Abiko, Kaoru; Mikami, Yoshiki; Kido, Aki; Baba, Tsukasa; Yoshioka, Yumiko; Yamaguchi, Ken; Matsumura, Noriomi; Konishi, Ikuo

    2014-11-01

    A uterus-like mass is an extrauterine mass with a cavity lined by endometrial tissue and a smooth muscle layer resembling the uterine corpus. It is a rare condition of unknown histogenesis. Herein, we describe a case of clear cell carcinoma arising from a uterus-like mass located in the retroperitoneal space. The patient, a 67-year old nulliparous woman, had been followed with the diagnosis of an ovarian endometriotic cyst for 14 years until ultrasonography and magnetic resonance imaging (MRI) demonstrated an enlargement of the cystic mass with a thickened irregular wall. Suspicion of malignant transformation prompted us to excise the lesion. At laparotomy, the uterus and right ovary appeared normal, and a mass measuring 8 cm was identified in the retroperitoneal space without any connection to the uterus. Grossly, the removed mass was composed of a cyst filled with blackish-brownish fluid and a thick wall resembling uterine myometrium. Microscopically, endometrial tissue inside the cyst, which was diffusely lined by clear cell carcinoma, was identified. Although the histogenesis of a uterus-like mass remains unclear, this case indicates that malignant tumors may occur from a uterus-like mass through the pathway similar to the carcinogenesis of endometriosis-related ovarian neoplasms.

  6. Clear Cell Adenocarcinoma of the Urethra: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2015-01-01

    Full Text Available Background. Clear cell adenocarcinoma of the urethra (CCAU is extremely rare and a number of clinicians may be unfamiliar with its diagnosis and biological behaviour. Aims. To review the literature on CCAU. Methods. Various internet databases were used. Results/Literature Review. (i CCAU occurs in adults and in women in the great majority of cases. (ii It has a particular association with urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; and probably does not arise by malignant transformation of nephrogenic adenoma. (iii It is usually, readily distinguished from nephrogenic adenoma because of greater cytological a-typicality and mitotic activity and does not stain for prostate-specific antigen or prostatic acid phosphatase. (iv It has been treated by anterior exenteration in women and cystoprostatectomy in men and at times by radiotherapy; chemotherapy has rarely been given. (v CCAU is aggressive with low 5-year survival rates. (vi There is no consensus opinion of treatment options that would improve the prognosis. Conclusions. Few cases of CCAU have been reported. Urologists, gynaecologists, pathologists, and oncologists should report cases of CCAU they encounter and enter them into a multicentric trial to determine the best treatment options that would improve the prognosis.

  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. 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.

  9. 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.

  10. Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature patient

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Christopher P. [Department of Orthopaedic Surgery, Madigan Army Medical Center, Ft. Lewis, WA (United States); Nelson, Scott D. [Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine, CA (United States); Seeger, Leanne L. [Department of Radiological Sciences, University of California, CA (United States); Eckardt, Jeffrey J. [Department of Orthopaedic Surgery, University of California, Los Angeles School of Medicine, CA (United States)

    2002-06-01

    We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral head of a 14-year-old skeletally immature boy. Radiographic examination revealed a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the patient's age and the radiographic appearance of the lesion, chondroblastoma was high on the differential diagnosis. A frozen section was performed at the time of open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS in a skeletally immature patient was felt to be unlikely, so curettage and bone grafting was performed. Final pathology review, however, confirmed the diagnosis of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection and hemiarthroplasty. (orig.)

  11. Clear Cell Adenocarcinoma Arising from Abdominal Wall Endometriosis

    Directory of Open Access Journals (Sweden)

    Thouraya Achach

    2008-01-01

    Full Text Available Endometriosis is a frequent benign disorder. Malignancy arising in extraovarian endometriosis is a rare event. A 49-year-old woman is presented with a large painful abdominal wall mass. She underwent a myomectomy, 20 years before, for uterus leiomyoma. Computed tomography suggested that this was a desmoid tumor and she underwent surgery. Histological examination showed a clear cell adenocarcinoma associated with endometriosis foci. Pelvic ultrasound, computed tomography, and endometrial curettage did not show any malignancy or endometriosis in the uterus and ovaries. Adjuvant chemotherapy was recommended, but the patient was lost to follow up. Six months later, she returned with a recurrence of the abdominal wall mass. She was given chemotherapy and then she was reoperated.

  12. Lymph node location of a clear cell hidradenoma: report of a patient and review of literature.

    Science.gov (United States)

    Tingaud, Claire; Costes, Valérie; Frouin, Eric; Delfour, Christophe; Cribier, Bernard; Guillot, Bernard; Szablewski, Vanessa

    2016-08-01

    Cutaneous clear cell hidradenoma is an uncommon benign adnexal tumor which is not supposed to metastasize, contrary to its rare malignant counterpart, hidradenocarcinoma. We report the case of a 49-year-old man, who had had a stable inguinal lymph node enlargement for 6 years. An excision was performed and revealed an intra-nodal tumor, made of large clear cells with abundant cytoplasm and round nuclei without atypia or mitosis. The immunohistochemical staining showed diffuse positivity for keratin AE1/AE3, keratin 5/6 and p63, and focal staining with keratin 7, epithelial membrane antigen (EMA) and carcinous epithelial antigen (CEA), which underlined some ductular structures. Tumor cells were negative for renal markers PAX8 and CD10. Ki67 stained less than 1% of tumor cells. A translocation involving MAML2 gene was evidenced by fluorescence in situ hybridization (FISH) analysis. No primary cutaneous tumor was found after extensive examination. Altogether, these results are in favor of an isolated nodal hidradenoma, for which we discuss two hypothesis: a primary nodal lesion, or a 'benign metastasis' of a cutaneous tumor. Cases of morphologically benign hidradenoma with lymph node involvement are exceptional. Our case, similar to every other reported case, was associated with an excellent prognosis, supporting the idea that these patients should not be overtreated. PMID:27080562

  13. 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

  14. 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...

  15. 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...

  16. Hemosiderotic clear-cell acanthoma: A pigmented mimicker

    Directory of Open Access Journals (Sweden)

    Leonardo Bugatti

    2011-01-01

    Full Text Available The authors report on a case of a 65-year-old man with pigmented clear-cell acanthoma located on the right thigh. Dermoscopy disclosed a peculiar picture consisting of diffuse black pigmentation with a superficial greyish veil in the central portion, dotted-to-globular dark red-black structures mainly located at the periphery with a homogenous regular reticular arrangement; peripheral translucid desquamation. Dermoscopic features are correlated with the histology, where hemosiderin deposits present in a sheet-like arrangement in the perivascular papillary dermis and in a band-like disposition in the reticular dermis at the base of the lesion can account for the pigmented picture. The lesion arose on a trauma-prone skin site; thus the authors believe that traumatic irritation may be responsible for the clinical and dermoscopic pictures, giving rise to a reaction similar in a way to the Auspitz′s sign provocated by trauma for psoriasis. Red blood cells extravasation from extremely superficialized capillaries may have led to hemosiderin deposition in the papillary and the reticular dermis.

  17. 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

  18. Targeted Therapies: Bevacizumab and interferon-alpha in metastatic renal-cell carcinoma.

    Science.gov (United States)

    Bukowski, Ronald M

    2009-05-01

    Rini and colleagues provide additional data on bevacizumab and interferon-alpha in clear-cell carcinoma of the kidney; a comparison of these results with the findings from contemporary trials suggests that bevacizumab and interferon-alpha is another clinically useful treatment option for patients with metastatic renal-cell carcinoma.

  19. 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)

  20. 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)

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    tumor-infiltrating immune cells at baseline and during treatment (P 180 cells/mm2) of on-treatment FOXP3-positive intratumoral immune cells were dead within 22 months (n = 11), whereas patients with low numbers (cells/mm2) of on-treatment......PURPOSE: The administration of interleukin-2 (IL-2) may increase the frequency of peripherally circulating FOXP3-positive regulatory immune cells, thus potentially compromising this treatment option for patients with metastatic renal cell carcinoma. The impact of IL-2-based therapy...... on the accumulation of FOXP3-positive immune cells in the tumor microenvironment in metastatic renal cell carcinoma is unknown. EXPERIMENTAL DESIGN: Baseline (n = 58) and on-treatment (n = 42) tumor core biopsies were prospectively obtained from patients with clear cell metastatic renal cell carcinoma before...

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

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiri [Department of Radiology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic)], E-mail: ferda@fnplzen.cz; Hora, Milan [Department of Urology, Charles University Hospital Plzen, Dr. Edvarda Benese 13, CZ-306 40 Plzen (Czech Republic); Hes, Ondrej [Institut of Pathology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Reischig, Tomas [Department of Internal Medicine, Nephrology Unit, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Kreuzberg, Boris; Mirka, Hynek; Ferdova, Eva; Ohlidalova, Kristyna; Baxa, Jan [Department of Radiology, Charles University Hospital Plzen, Alej Svobody 80, CZ-306 40 Plzen (Czech Republic); Urge, Tomas [Department of Urology, Charles University Hospital Plzen, Dr. Edvarda Benese 13, CZ-306 40 Plzen (Czech Republic)

    2007-08-15

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

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

    Directory of Open Access Journals (Sweden)

    A.-S. Paşca

    2013-10-01

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

  4. Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury

    Directory of Open Access Journals (Sweden)

    Jia Xiaohua

    2012-09-01

    Full Text Available Abstract Background Bone marrow (BM stem cells have been reported to contribute to tissue repair after kidney injury model. However, there is no direct evidence so far that BM cells can trans-differentiate into renal stem cells. Methods To investigate whether BM stem cells contribute to repopulate the renal stem cell pool, we transplanted BM cells from transgenic mice, expressing enhanced green fluorescent protein (EGFP into wild-type irradiated recipients. Following hematological reconstitution and ischemia-reperfusion (I/R, Sca-1 and c-Kit positive renal stem cells in kidney were evaluated by immunostaining and flow cytometry analysis. Moreover, granulocyte colony stimulating factor (G-CSF was administrated to further explore if G-CSF can mobilize BM cells and enhance trans-differentiation efficiency of BM cells into renal stem cells. Results BM-derived cells can contribute to the Sca-1+ or c-Kit+ renal progenitor cells population, although most renal stem cells came from indigenous cells. Furthermore, G-CSF administration nearly doubled the frequency of Sca-1+ BM-derived renal stem cells and increased capillary density of I/R injured kidneys. Conclusions These findings indicate that BM derived stem cells can give rise to cells that share properties of renal resident stem cell. Moreover, G-CSF mobilization can enhance this effect.

  5. 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

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

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    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.

  7. Relationship between blood flow grade detected by three - dimensional color Doppler and vascular density in renal clear cell carcinoma%三维彩色超声检测肾透明细胞癌中血流等级与血管密度的关系

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    张瑞虹; 赵杰; 李向沛; 党磊

    2011-01-01

    Objective To investigate the diagnostic value of three - dimensional color Doppler in renal clear cell carcinoma ( RCCC ), study the relationship between blood flow grade and vascular density in order to provide theoretical references for clinical practice. Methods The clinical data of 110 patients confirmed as RCCC in our hospital were collected in this study. All of them received three - dimensional color Doppler examination preoperatively, and the ultrasonic blood flow was graded according to corresponding criteria. The vascular density of RCCC was measured by CD34 marking postoperatively. The relationship between blood flow grade and vascular density was analyzed eventually. Results Ultrasonic diagnosis in 102 cases was coincident with postoperative pathological diagnosis,and the coincidence rate was 92.73%. There was a positive correlation between flood flow grade and vascular density in RCCC( P < 0.05 ). Conclusion The preoperative detection of blood flow grade by three - dimensional color Doppler is of high value in the diagnosis of RCCC. Blood flow grade can reflect the vascular density preoperatively, which may be helpful to predict the prognosis and guide the treatment of RCCC.%目的 探讨三维彩色多普勒超声对肾透明细胞癌的诊断价值,观察其血流等级与肾透明细胞癌中血管密度的关系,以期为临床诊疗提供参考.方法 收集我院确诊为肾透明细胞癌的110例的三维彩色多普勒超声资料,观察肾透明细胞癌的超声特征,探讨血流等级与术后CD34标记肿瘤中血管密度的关系.结果 110例中,超声诊断102例与术后病理符合,符合率为92.73%.彩色多普勒检测肾透明细胞癌中的血流等级与肿瘤中的血管密度呈正相关.结论 三维彩色多普勒超声检测血流等级对肾透明细胞癌具有较高的术前诊断价值,术前检测血流等级可以反映肾透明细胞癌的血管密度情况,对于判断肿瘤预后和指导临床治疗有一定价值.

  8. 肾透明细胞癌的CT表现与Ki67、MVD、P73表达的相关性研究%A Correlative Study between CT Features and the Expression of Ki67 and MVD,P73 in Clear Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    杨毅; 周俊林; 郭玲; 董驰

    2015-01-01

    Objective To study the correlation between CT features and the expression of Ki67 and MVD, P73 in clear renal cell carcinoma (CCCRCC). So as to evaluate CT features of CCRCC and its biological behaviour. Methods To analyse the CT features of 30 cases with CCRCC which were confirmed by operation and pathology . The expression of MVD, Ki67, P73 of the collected organic material were confirmed by Immunohistochemical staining.then analized the relationship between CT features and the expression of MVD and Ki67, P73. Results 1,The expression of Ki67, MVD, P73 and MVD of CCRCC are positively related to the tumor boundary, the largest enhanced degree, the biggest tumors size (P0.05).There is no statistical difference between calcification and the expression of Ki67, MVD, P73 (P>0.05). Conclusion 1, An accurate preoperative diagnosis of CCRCC can be made by MSCT scanning. 2, Some of CT features of CCRCC have correlation with the expression of Ki67, MVD and P73, it illustrate that CT manifestation of CCRCC may reflect the biological characteristic of the tumors partly.%目的:探讨肾透明细胞癌的CT表现与Ki67、MVD、P73表达的相关性,通过CT表现评价其部分生物学行为。方法分析经手术病理证实的30例肾透明细胞癌的CT表现,同时对其进行相关免疫组化染色,分析肾透明细胞癌的CT表现及其与MVD、Ki67、P73表达的相关性。结果肾透明细胞癌中的囊变坏死、肿瘤边界、最大强化程度及大小均与Ki67、MVD、P73表达正相关(P0.05),钙化与Ki67、MVD、P73表达无统计学差异(P>0.05)。结论1、通过MSCT扫描,可以对肾透明细胞癌进行比较准确的术前诊断。2、肾透明细胞癌的部分CT征象与Ki67、MVD、P73的表达具有相关性,可能在一定程度反映出肿瘤的生物学特性。

  9. Cadherin-9 is a novel cell surface marker for the heterogeneous pool of renal fibroblasts.

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    Cornelia Thedieck

    Full Text Available BACKGROUND: Interstitial fibroblasts are a minor, but nevertheless very important, component of the kidney. They secrete and remodel extracellular matrix and they produce active compounds such as erythropoietin. However, studying human renal fibroblasts has been hampered by the lack of appropriate surface markers. METHODS AND FINDINGS: The expression of cadherin-9 in various human renal cell lines and tissues was studied on the mRNA level by RT-PCR and on the protein level with the help of newly generated cadherin-9 antibodies. The classical type II cadherin-9, so far only described in the neural system, was identified as a reliable surface marker for renal fibroblasts. Compared to FSP1, a widely-used cytosolic renal fibroblast marker, cadherin-9 showed a more restricted expression pattern in human kidney. Under pathological conditions, cadherin-9 was expressed in the stroma of renal cell carcinoma, but not in the tumor cells themselves, and in renal fibrosis the percentage of cadherin-9-positive cells was clearly elevated 3 to 5 times compared to healthy kidney tissue. Induction of epithelial mesenchymal transition in renal epithelial cells with cyclosporin-A, which causes renal fibrosis as a side effect, induced cadherin-9 expression. Functional studies following siRNA-mediated knockdown of cadherin-9 revealed that it acts in the kidney like a typical classical cadherin. It was found to be associated with catenins and to mediate homophilic but not heterophilic cell interactions. CONCLUSIONS: Cadherin-9 represents a novel and reliable cell surface marker for fibroblasts in healthy and diseased kidneys. Together with the established marker molecules FSP1, CD45 and alpha smooth muscle actin, cadherin-9 can now be used to differentiate the heterogenic pool of renal fibroblasts into resident and activated fibroblasts, immigrated bone marrow derived fibroblast precursors and cells in different stages of epithelial mesenchymal transition.

  10. Hepatocellular Carcinoma with Foamy Histiocyte-Like Appearance: A Deceptively Clear Cell Carcinoma Appearing Variant

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    Takuji Noro

    2010-08-01

    Full Text Available Hepatocellular carcinoma (HCC shows many pathological features, and it varies architecturally and cytologically. There have been many reports and discussions of the morphological features of HCC. A 63-year-old man was found to have a solitary tumor in liver segment 7 that was diagnosed as HCC. A partial resection of liver segment 7 was performed. Microscopically, the tumor lesion showed a moderately differentiated HCC. There was also a lesion with foamy histiocyte-like cells corresponding to the white lesion in the face of the cut tumor. Immunohistochemical staining showed that they were negative for CD68, S-100, vimentin, and HMB-45. The cytoplasm itself was negative on periodic acid Schiff (PAS and Sudan staining. Without immunohistological analysis, it is difficult to distinguish this HCC variant from clear cell carcinoma or metastases of renal cell carcinoma. It is important to recognize this type as a specific cytological variant of HCC that requires confirmation by immunohistochemistry. This report describes the case of a patient with a morphologically distinctive pattern of HCC with prominent cell cytoplasm that had a foamy histiocyte-like appearance. To the best of our knowledge, this is the first report of this HCC variant.

  11. Stem cells and progenitor cells in renal disease.

    Science.gov (United States)

    Haller, Hermann; de Groot, Kirsten; Bahlmann, Ferdinand; Elger, Marlies; Fliser, Danilo

    2005-11-01

    Stem cells and progenitor cells are necessary for repair and regeneration of injured renal tissue. Infiltrating or resident stem cells can contribute to the replacement of lost or damaged tissue. However, the regulation of circulating progenitor cells is not well understood. We have analyzed the effects of erythropoietin on circulating progenitor cells and found that low levels of erythropoietin induce mobilization and differentiation of endothelial progenitor cells. In an animal model of 5/6 nephrectomy we could demonstrate that erythropoietin ameliorates tissue injury. Full regeneration of renal tissue demands the existence of stem cells and an adequate local "milieu," a so-called stem cell niche. We have previously described a stem cell niche in the kidneys of the dogfish, Squalus acanthus. Further analysis revealed that in the regenerating zone of the shark kidney, stem cells exist that can be induced by loss of renal tissue to form new glomeruli. Such animal models improve our understanding of stem cell behavior in the kidney and may eventually contribute to novel therapies. PMID:16221168

  12. Reduced cilia frequencies in human renal cell carcinomas versus neighboring parenchymal tissue

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    Basten Sander G

    2013-01-01

    . Cilia frequencies in a total of eighty-nine clear cell, eight papillary, five chromophobe renal cell carcinomas, two sarcomatoid renal tumors and six oncocytomas were determined. A marked decrease of primary cilia across renal cell carcinoma subtypes was observed compared to adjacent nontumorigenic tissue. Conclusions Our study shows that cilia are predominantly lost in renal cell carcinomas compared to tissue of the tumor parenchyma. These results suggest that ciliary loss is common in renal tumorigenesis, possibly participating in the sequence of cellular events leading to malignant tumor development. Future therapies aimed at restoring or circumventing cilia signaling might therefore aid in current treatment efficacy.

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

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    Saby George

    2009-08-01

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

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

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    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.

  15. Renal cell carcinoma: links and risks

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    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

  16. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.

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    Cynthia A Batchelder

    Full Text Available Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease.

  17. Bilateral acrometastasis in a case renal cell carcinoma

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    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

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

    DEFF Research Database (Denmark)

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

    Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made...

  19. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case.

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    Badrashetty, Dinesh; Rangaswamy, Shruthi; Belgode, Niranjan

    2013-09-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign tumor of the jaws. Pindborg's tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior.

  20. Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible

    Institute of Scientific and Technical Information of China (English)

    Ching-Yi Chen; Chung-Wei Wu; Wen-Chen Wang; Li-Min Lin; Yuk-Kwan Chen

    2013-01-01

    We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.

  1. Clear cell variant of intraosseous mucoepidermoid carcinoma: Report of a rare entity

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    Sujatha Varma

    2012-01-01

    Full Text Available Intraosseous mucoepidermoid carcinoma of jaw bones is a rare lesion. Abundance of clear cells in an intraosseous mucoepidermoid carcinoma may complicate its histopathologic diagnosis. It becomes extremely important to distinguish this lesion from other clear cell lesions of jaw region. Here, we report a case of clear cell variant of intraosseous mucoepidermoid carcinoma in the mandible.

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

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    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.

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

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    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

  4. 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....

  5. 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.

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

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

    2009-01-01

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

  7. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer

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    Jung Klaus

    2008-12-01

    Full Text Available Abstract Background Enhanced activity of histone deacetylases (HDAC is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. Methods We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Results Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Conclusion Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies.

  8. Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer

    International Nuclear Information System (INIS)

    Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. [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

  16. 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.

  17. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

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

    2016-01-01

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

  18. Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure.

    OpenAIRE

    Humes, H D; Cieslinski, D A; T.M. Coimbra; Messana, J M; Galvao, C.

    1989-01-01

    To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, bega...

  19. 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

  20. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    Science.gov (United States)

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  1. Isolated renal metastasis from squamous cell lung cancer

    Directory of Open Access Journals (Sweden)

    Cai Jun

    2013-01-01

    Full Text Available Abstract Renal metastasis from non-small cell lung cancer is rather uncommon. The mechanism underlying the occurrence of metastasis in this site is still not well understood. We report a case of a 53-year-old Chinese woman who had moderately differentiated squamous cell carcinoma of the lung. After a ten months post-surgery interval of disease free survival, computed tomography (CT scan found that left renal parenchymal was occupied by a mass, confirmed by kidney biopsy to be a metastasis from squamous cell lung carcinoma. Based on this case, we are warned to be cautious in diagnosis and treatment when renal lesion are detected.

  2. Thyroid Regeneration: Characterization of Clear Cells After Partial Thyroidectomy

    OpenAIRE

    Ozaki, Takashi; Matsubara, Tsutomu; Seo, Daekwan; Okamoto, Minoru; Nagashima, Kunio; Sasaki, Yoshihito; Hayase, Suguru; Murata, Tsubasa; Liao, Xiao-Hui; Hanson, Jeffrey; Rodriguez-Canales, Jaime; Thorgeirsson, Snorri S.; Kakudo, Kennichi; Refetoff, Samuel; Kimura, Shioko

    2012-01-01

    Although having the capacity to grow in response to a stimulus that perturbs the pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ. In this study, partial thyroidectomy (PTx) was used to produce a condition for thyroid regeneration. In the intact thyroid gland, the central areas of both lobes served as the proliferative centers where microfollicles, and bromodeoxyuridine (BrdU)-positive and/or C cells, were localized. Two weeks after PTx, the number of BrdU-posi...

  3. H-ras-transformed NRK-52E renal epithelial cells have altered growth, morphology, and cytoskeletal structure that correlates with renal cell carcinoma in vivo.

    Science.gov (United States)

    Best, C J; Tanzer, L R; Phelps, P C; Merriman, R L; Boder, G G; Trump, B F; Elliget, K A

    1999-04-01

    We studied the effect of the ras oncogene on the growth kinetics, morphology, cytoskeletal structure, and tumorigenicity of the widely used NRK-52E rat kidney epithelial cell line and two H-ras oncogene-transformed cell lines, H/1.2-NRK-52E (H/1.2) and H/6.1-NRK-52E (H/6.1). Population doubling times of NRK-52E, H/1.2, and H/6.1 cells were 28, 26, and 24 h, respectively, with the transformed cells reaching higher saturation densities than the parent cells. NRK-52E cells had typical epithelial morphology with growth in colonies. H/1.2 and H/6.1 cell colonies were more closely packed, highly condensed, and had increased plasma membrane ruffling compared to parent cell colonies. NRK-52E cells showed microfilament, microtubule, and intermediate filament networks typical of epithelial cells, while H/1.2 and H/6.1 cells showed altered cytoskeleton architecture, with decreased stress fibers and increased microtubule and intermediate filament staining at the microtubule organizing center. H/1.2 and H/6.1 cells proliferated in an in vitro soft agar transformation assay, indicating anchorage-independence, and rapidly formed tumors in vivo with characteristics of renal cell carcinoma, including mixed populations of sarcomatoid, granular, and clear cells. H/6.1 cells consistently showed more extensive alterations of growth kinetics, morphology, and cytoskeleton than H/1.2 cells, and formed tumors of a more aggressive phenotype. These data suggest that analysis of renal cell characteristics in vitro may have potential in predicting tumor behavior in vivo, and significantly contribute to the utility of these cell lines as in vitro models for examining renal epithelial cell biology and the role of the ras proto-oncogene in signal transduction involving the cytoskeleton.

  4. Clear cell variant of diffuse large B-cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Sahatciu-Meka Vjollca

    2011-05-01

    Full Text Available Abstract Introduction Diffuse large B-cell lymphoma is a diffuse proliferation of large neoplastic B lymphoid cells with a nuclear size equal to or exceeding the normal macrophage nuclei. We report a case of a clear cell variant of diffuse large B-cell lymphoma involving a lymph node in the neck, which was clinically suspected of being metastatic carcinoma. Case presentation A 39-year-old Caucasian ethnic Albanian man from Kosovo presented with a rapidly enlarging lymph node in his neck, but he also disclosed B symptoms and fatigue. A cytological aspirate of the lymph node revealed pleomorphic features. Our patient underwent a cervical lymph node biopsy (large excision. The mass was homogeneously fish-flesh, pale white tissue replacing almost the whole structure of the lymph node. The lymph node biopsy showed a partial alveolar growth pattern, which raised clinical suspicion that it was an epithelial neoplasm. With regard to morphological and phenotypic features, we discovered large nodules in diffuse areas, comprising large cells with slightly irregular nuclei and clear cytoplasm admixed with a few mononuclear cells. In these areas, there was high mitotic activity, and in some areas there were macrophages with tangible bodies. Staining for cytokeratins was negative. These areas had the following phenotypes: cluster designation marker 20 (CD20 positive, B-cell lymphoma (Bcl-2-positive, Bcl-6-, CD5-, CD3-, CD21+ (in alveolar patterns, prostate-specific antigen-negative, human melanoma black marker 45-negative, melanoma marker-negative, cytokeratin-7-negative and multiple myeloma marker 1-positive in about 30% of cells, and exhibited a high proliferation index marker (Ki-67, 80%. Conclusion According to the immunohistochemical findings, we concluded that this patient has a clear cell variant of diffuse large B-cell lymphoma of activated cell type, post-germinal center cell origin. Our patient is undergoing R-CHOP chemotherapy treatment.

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

    Science.gov (United States)

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

    2013-04-01

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

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

    Science.gov (United States)

    ... Central Sudarshan S, Pinto PA, Neckers L, Linehan WM. Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer-- ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  7. Clear cell variant of calcifying epithelial odontogenic tumor of maxilla: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Dinesh Badrashetty

    2013-01-01

    Full Text Available The calcifying epithelial odontogenic tumor (CEOT is a rare benign tumor of the jaws. Pindborg′s tumor having clear cells is extremely rare. Twelve central lesions have been reported of which only three cases have occurred in maxilla. Clear cell variant is a distinct entity, has more aggressive biological behavior and higher chances of recurrence. Hence it is important that presence of clear cells be included in histopathological diagnosis. Here we present a rare case of clear cell CEOT having aggressive behavior.

  8. 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.

  9. Renal Cell Carcinoma Presenting with Paraneoplastic Hallucinations and Cognitive Decline from Limbic Encephalitis.

    Science.gov (United States)

    Harrison, Joshua W; Cherukuri, Ramesh; Buchan, Debra

    2015-07-01

    We present a 66-year-old woman with 2 months of visual hallucinations, unintentional weight loss, and short-term memory decline, whose clinical presentation and EEG supported a diagnosis of limbic encephalitis. Subsequent evaluation for a paraneoplastic etiology revealed a renal mass, which was resected and identified as clear cell renal carcinoma. The patient's clinical condition improved after resection of the mass. When patients present with incongruous subacute neuropsychiatric symptoms, clinicians should be mindful of paraneoplastic neurological disorders, as early diagnosis and treatment of malignancy may lead to symptomatic improvement.

  10. Renalase's expression and distribution in renal tissue and cells.

    Directory of Open Access Journals (Sweden)

    Feng Wang

    Full Text Available To study renalase's expression and distribution in renal tissues and cells, renalase coded DNA vaccine was constructed, and anti-renalase monoclonal antibodies were produced using DNA immunization and hybridoma technique, followed by further investigation with immunological testing and western blotting to detect the expression and distribution of renalase among the renal tissue and cells. Anti-renalase monoclonal antibodies were successfully prepared by using DNA immunization technique. Further studies with anti-renalase monoclonal antibody showed that renalase expressed in glomeruli, tubule, mesangial cells, podocytes, renal tubule epithelial cells and its cells supernatant. Renalase is wildly expressed in kidney, including glomeruli, tubule, mesangial cells, podocytes and tubule epithelial cells, and may be secreted by tubule epithelial cells primarily.

  11. Renal cell carcinoma arising in ipsilateral duplex system.

    Science.gov (United States)

    Mohan, Harsh; Kundu, Reetu; Dalal, Usha

    2014-09-01

    Congenital anomalies of the kidney and urinary tract are common and include a wide anatomic spectrum. Duplex systems are one of the more common renal anomalies, with the majority being asymptomatic. Little is known about the molecular pathogenesis of these anomalies; however, certain causative genes have been implicated. The finding of renal cell carcinoma arising in a kidney with the duplication of pelvicalyceal system and ureters, as in the present case, is uncommon. The association between a duplex system and renal cell carcinoma may be more than a coincidence, requiring a deeper insight and further elucidation. PMID:26328175

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    Lipworth Loren

    2011-04-01

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

  14. 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.

  15. 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

  16. 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.

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

    OpenAIRE

    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...

  18. Renal erythropoietin-producing cells in health and disease

    Directory of Open Access Journals (Sweden)

    Tomokazu eSouma

    2015-06-01

    Full Text Available Erythropoietin (Epo is an indispensable erythropoietic hormone primarily produced from renal Epo-producing cells (REPs. Epo production in REPs is tightly regulated in a hypoxia-inducible manner to maintain tissue oxygen homeostasis. Insufficient Epo production by REPs causes renal anemia and anemia associated with chronic disorders. Recent studies have broadened our understanding of REPs from prototypic hypoxia-responsive cells to dynamic fibrogenic cells. In chronic kidney disease, REPs are the major source of scar-forming myofibroblasts and actively produce fibrogenic molecules, including inflammatory cytokines. Notably, myofibroblast-transformed REPs recover their original physiological properties after resolution of the disease insults, suggesting that renal anemia and fibrosis could be reversible to some extent. Therefore, understanding the plasticity of REPs will lead to the development of novel targeted therapeutics for both renal fibrosis and anemia. This review summarizes the regulatory mechanisms how hypoxia-inducible Epo gene expression is attained in health and disease conditions.

  19. Clear Cell Sarcoma of Gluteal Region Malignant Melanoma of Soft Parts

    Directory of Open Access Journals (Sweden)

    Haren V. Oza

    2013-04-01

    Full Text Available Clear cell sarcoma (CCS is described as variant of sarcoma characterized by prominent clear cells showing features similar to malignant melanoma of soft parts. This neoplasm was first described by Dr. Franz m. Enzinger. Primary CCS usually arises in deeper soft tissues, in association with fascia, tendons, or aponeuroses. Clear cell sarcoma (CCS is a rare malignant tumor with a propensity for slow progressive invasion. It is a tumor derived from Melanoblast like cell. They occur most commonly in the extremities, with a predilection for young females. Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultra structural level. The tumor is very rare and can pose clinical challenges in early diagnosis. This case report demonstrates an unusual site of occurrence for clear cell sarcoma. [Natl J Med Res 2013; 3(2.000: 193-195

  20. Nuclear factor XIIIa staining (clone AC-1A1 mouse monoclonal) is a sensitive and specific marker to discriminate sebaceous proliferations from other cutaneous clear cell neoplasms.

    Science.gov (United States)

    Uhlenhake, Elizabeth E; Clark, Lindsey N; Smoller, Bruce R; Shalin, Sara C; Gardner, Jerad M

    2016-08-01

    Sebaceous carcinoma is a rare but serious malignancy that may be difficult to diagnose when poorly differentiated. Other epithelial tumors with clear cell change may mimic sebaceous carcinoma. Few useful or specific immunohistochemical markers for sebaceous differentiation are available. Nuclear staining with factor XIIIa (clone AC-1A1) was recently found to be a highly sensitive marker of sebaceous differentiation. We evaluated nuclear factor XIIIa (AC-1A1) staining in sebaceous neoplasms vs. other cutaneous clear cell tumors. We stained 27 sebaceous proliferations: sebaceous hyperplasia (7), sebaceous adenoma (8), sebaceoma (5), sebaceous carcinoma (7). We also stained 67 tumors with clear cell change: basal cell carcinoma (8), squamous cell carcinoma (8), hidradenoma (7), desmoplastic trichilemmoma (2), trichilemmoma (10), trichilemmal carcinoma (3), clear cell acanthoma (9), atypical fibroxanthoma (1), syringoma (8), trichoepithelioma (1), metastatic renal cell carcinoma (2), and nevi with balloon cell change (8). Nuclear factor XIIIa (AC-1A1) staining was present in 100% of sebaceous proliferations; 96% displayed strong staining. Non-sebaceous clear cell tumors were negative or only weakly positive with factor XIIIa (AC-1A1) in 95.5%; only 4.5% showed strong staining. This suggests that strong nuclear factor XIIIa (AC-1A1) staining is a sensitive and specific marker of sebaceous neoplasms vs. other clear cell tumors.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Hoti Lal

    2015-11-01

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

  3. Apoptotic Cells Are Cleared by Directional Migration and elmo1-Dependent Macrophage Engulfment

    NARCIS (Netherlands)

    van Ham, Tjakko J.; Kokel, David; Peterson, Randall T.

    2012-01-01

    Apoptotic cell death is essential for development and tissue homeostasis [1, 2]. Failure to clear apoptotic cells can ultimately cause inflammation and autoimmunity [3, 4]. Apoptosis has primarily been studied by staining of fixed tissue sections, and a clear understanding of the behavior of apoptot

  4. Patterns of spread of clear cell ovarian cancer: Case report and case series ☆

    OpenAIRE

    Kumar, Aalok; Gilks, C. Blake; Mar, Colin; Santos, Jennifer; Tinker, Anna V.

    2013-01-01

    Highlights • Although patterns of metastases in ovarian clear cell cancer are not well described, patients may initially present with bone metastases. • Clear cell carcinoma with bone metastases is responsive to radiation therapy. • Bone metastases are not common in patients with ovarian high grade serous cancer.

  5. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

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

  6. 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.

  7. 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.

  8. Epidemiologic characteristics of renal cell carcinoma in Brazil

    Directory of Open Access Journals (Sweden)

    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.

  9. Sorafenib and sunitinib: novel targeted therapies for renal cell cancer.

    Science.gov (United States)

    Grandinetti, Cheryl A; Goldspiel, Barry R

    2007-08-01

    Renal cell cancer (RCC) is a relatively uncommon malignancy, with 51,190 cases expected to be diagnosed in 2007. Localized disease is curable by surgery; however, locally advanced or metastatic disease is not curable in most cases and, until recently, had a limited response to drug treatment. Historically, biologic response modifiers or immunomodulating agents were tested in clinical trials based on observations that some cases of RCC can spontaneously regress. High-dose aldesleukin is approved by the United States Food and Drug Administration as a treatment for advanced RCC; however, the drug is associated with a high frequency of severe adverse effects. Responses have been observed with low-dose aldesleukin and interferon alfa, but with little effect on overall survival. Sorafenib and sunitinib are novel therapies that target growth factor receptors known to be activated by the hypoxia-inducible factor and the Ras-Raf/MEK/ERK pathways. These pathways are important in the pathophysiology of RCC. Sorafenib and sunitinib have shown antitumor activity as first- and second-line therapy in patients with cytokine-refractory metastatic RCC who have clear-cell histology. Although complete responses are not common, both drugs promote disease stabilization and increase progression-free survival. This information suggests that disease stabilization may be an important determinant for response in RCC and possibly other cancers. Sorafenib and sunitinib are generally well tolerated and are considered first- and second-line treatment options for patients with advanced clear cell RCC. In addition, sorafenib and sunitinib have shown promising results in initial clinical trials evaluating antitumor activity in patients who are refractory to other antiangiogenic therapy. The most common toxicities with both sorafenib and sunitinib are hand-foot syndrome, rash, fatigue, hypertension, and diarrhea. Research is directed toward defining the optimal use of these new agents. PMID:17655513

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  11. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman

    OpenAIRE

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her ser...

  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. Inactivation of the von Hippel-Lindau tumour suppressor gene induces Neuromedin U expression in renal cancer cells

    Directory of Open Access Journals (Sweden)

    Shukla Deepa

    2011-07-01

    Full Text Available Abstract Background 209 000 new cases of renal carcinoma are diagnosed each year worldwide and new therapeutic targets are urgently required. The great majority of clear cell renal cancer involves inactivation of VHL, which acts as a gatekeeper tumour suppressor gene in renal epithelial cells. However how VHL exerts its tumour suppressor function remains unclear. A gene expression microarray comparing RCC10 renal cancer cells expressing either VHL or an empty vector was used to identify novel VHL regulated genes. Findings NMU (Neuromedin U is a neuropeptide that has been implicated in energy homeostasis and tumour progression. Here we show for the first time that VHL loss-of-function results in dramatic upregulation of NMU expression in renal cancer cells. The effect of VHL inactivation was found to be mediated via activation of Hypoxia Inducible Factor (HIF. Exposure of VHL expressing RCC cells to either hypoxia or dimethyloxalylglycine resulted in HIF activation and increased NMU expression. Conversely, suppression of HIF in VHL defective RCC cells via siRNA of HIF-α subunits or expression of Type 2C mutant VHLs reduced NMU expression levels. We also show that renal cancer cells express a functional NMU receptor (NMUR1, and that NMU stimulates migration of renal cancer cells. Conclusions These findings suggest that NMU may act in an autocrine fashion, promoting progression of kidney cancer. Hypoxia and HIF expression are frequently observed in many non-renal cancers and are associated with a poor prognosis. Our study raises the possibility that HIF may also drive NMU expression in non-renal tumours.

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

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Dagnæs-Hansen, Frederik; Toft, Palle

    2010-01-01

    Acute renal failure (ARF) is a common morbidity factor among patients in the intensive care unit, reaching an incidence from 3% to 30% depending on the definition of ARF and the population. Although the majority of the patients with ARF are treated with continuous renal replacement therapy......, the mortality rate still remains above 50%. The causes of death are primarily extra-renal and include infection, shock, septicemia, and respiratory failure. We wanted to evaluate the cell-mediated inflammatory response of renal ischemia-reperfusion (I/R) and non-renal I/R, in blood and in distant organs. In our...... the inflammatory response, we measured myeloperoxidase (MPO) in the organs, and CD 11b and major histocompatibility complex (MHC) II-positive cells in the blood. Non-renal I/R elicited the most elevated levels of MPO in extra-renal tissue such as the lungs. There was a trend toward higher MPO levels in the kidney...

  15. AE-941, a multifunctional antiangiogenic compound: trials in renal cell carcinoma.

    Science.gov (United States)

    Bukowski, Ronald M

    2003-08-01

    The therapy of renal cell carcinoma remains a challenge for medical oncologists and urologists. During the past 10 years, the molecular abnormalities occurring in various subtypes of renal cancer, such as clear cell renal carcinoma, have been well described. The genetic abnormalities found in clear cell tumours involve chromosome 3p and, additionally, hypermethylation of the von Hippel-Lindau (VHL) gene can be detected. The VHL protein is involved in the angiogenic cascade in non-hypoxic conditions, and the possible role of mutant or hypermethylated VHL protein in promoting angiogenesis is, therefore, of interest. The majority of patients with renal cell carcinoma who receive treatment, such as IL-2 and/or IFN, fail and develop progressive disease. Therapy is therefore inadequate and novel approaches, such as those inhibiting angiogenesis, are of interest. The agent AE-941 (Neovostat trade mark; AEterna) was developed based on the observation that shark cartilage may contain biologically active inhibitors of angiogenesis. A variety of in vitro and in vivo activities of this preparation have been identified. At the molecular level, AE-941 appears to exhibit four different potential mechanisms of action: modulation of matrix proteases; inhibition of vascular endothelial growth factor binding to its receptor; induction of endothelial cell apoptosis; and stimulation of angiostatin production. The antitumour effects of AE-941 are seen in multiple murine models and involve not only effects on primary tumour growth but also on development of metastases. AE-941 is administered orally and has an excellent toxicity profile. Of interest are the findings in patients with renal cell carcinoma. Preliminary trials in this setting have suggested that responses to AE-941 occur and that patients receiving higher doses of this agent may have improved survival. Based on these preliminary data, a large, multi-institutional, randomised, Phase III trial of this agent has now been

  16. Using Molecular Biology to Develop Drugs for Renal Cell Carcinoma

    Science.gov (United States)

    Cowey, C. Lance; Rathmell, W. Kimryn

    2010-01-01

    Background Renal cell carcinoma is a disease marked by a unique biology which has governed it’s long history of poor response to conventional cancer treatments. The discovery of the signaling pathway activated as a result of inappropriate constitutive activation of the hypoxia inducible factors (HIF), transcription factors physiologically and transiently stabilized in response to low oxygen, has provided a primary opportunity to devise treatment strategies to target this oncogenic pathway. Objective A review of the molecular pathogenesis of renal cell cancer as well as molecularly targeted therapies, both those currently available and those in development, will be provided. In addition, trials involving combination or sequential targeted therapy are discussed. Methods A detailed review of the literature describing the molecular biology of renal cell cancer and novel therapies was performed and summarized. Results/Conclusion Therapeutics targeting angiogenesis have provided the first class of agents which provide clinical benefit in a large majority of patients and heralded renal cell carcinoma as a solid tumor paradigm for the development of novel therapeutics. Multiple strategies targeting this pathway and now other identified pathways in renal cell carcinoma provide numerous potential opportunities to make major improvements in treating this historically devastating cancer. PMID:20648240

  17. Imaging features of clear-cell ependymoma of the spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Bapuraj, J.R.; Parmar, Hemant A. [University of Michigan, Department of Radiology, Ann Arbor, MI (United States); Blaivas, Mila [University of Michigan Health System, Department of Neuropathology, Ann Arbor, MI (United States); Muraszko, Karin M. [University of Michigan Health System, Department of Neurosurgery, Ann Arbor, MI (United States)

    2007-04-15

    A 10-year-old girl presented with increasing lower back pain without gait or sphincter disturbances. MRI demonstrated a large, intramedullary tumor at the level of the conus. The imaging findings were unlike those of a classic ependymoma or astrocytoma. Histopathologic examination demonstrated clear-cell ependymoma, which is a distinct entity. We found three cases of clear-cell ependymoma of the spinal cord reported in the literature. Clear-cell ependymoma of the spinal cord can be resected completely and needs to be recognized for its imaging features, benign course and favorable prognosis. (orig.)

  18. Clear cell adenocarcinoma of a female urethra: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Amel Trabelsi

    2009-01-01

    Full Text Available Context : Clear cell adenocarcinoma of the urethra is an extremely rare tumour. Its histogenetic derivation remains controversial. Case report : We report a new case of clear cell adenocarcinoma of the proximal urethra in a 56-year-old woman who presented with grossly hematuria. Urethral cystoscopy revealed a tumour protruding from the posterior urethral wall at the bladder neck. Treatment consisted of urethrocystectomy with pelvic lymph node dissection. Histologically, the neoplasm consisted of clear cell adenocarcinoma of the urethra. Conclusion : It appears that female urethral adenocarcinoma has more than one tissue of origin.

  19. [ANEURYSMAL TYPE RENAL ARTERIOVENOUS FISTULA WITH GIANT VENOUS ANEURYSM, MIMICKING RENAL CELL CARCINOMA: A CASE REPORT].

    Science.gov (United States)

    Nagumo, Yoshiyuki; Komori, Hiroka; Rii, Jyunryo; Ochi, Atsuhiko; Suzuki, Koichiro; Shiga, Naoki; Ota, Tomonori

    2015-04-01

    A 39-year-old man was referred to our clinic for a 7 cm tumor in the right kidney, found by simple CT scan. It was suspected as renal cell carcinoma accompanying tumor emboli in the inferior vena cava by enhanced CT scan. For further evaluation of the tumor emboli, color Doppler ultrasound and enhanced MRI was performed. They showed a large cystic lesion with high velocity turbulent flow and flow voids in T2-weighted imaging, it seemed as giant venous aneurysm of the right renal vein. Subsequently, angiography revealed aneurysmal type renal arteriovenous fistula (AVF), transarterial embolization (TAE) of the arterial feeder with coils was performed on the same day. After 6 months from embolization, there was no recurrences or reinterventions. Color Doppler ultrasound and MRI are beneficial in distinguishing vascular disease from neoplastic disease which may sometimes mimick in other diagnostic imaging studies. In addition TAE seems to be an effective treatment for the AVF. PMID:26415363

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Cherry, E-mail: cherrykim0505@gmail.com; Choi, Hyuck Jae, E-mail: choihj@amc.seoul.kr; Cho, Kyoung-Sik, E-mail: kscho@amc.seoul.kr

    2014-06-15

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

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

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal;

    2014-01-01

    and statistical analysisBiomarker association with CSS was analysed by univariate and multivariate analyses. Results and limitationsA total of 17 of 28 biomarkers (TP53 mutations; amplifications of chromosomes 8q, 12, 20q11.21q13.32, and 20 and deletions of 4p, 9p, 9p21.3p24.1, and 22q; low EDNRB and TSPAN7...... that were significant in univariate analysis were enriched, and chromosomal instability indices were increased in samples expressing the ccB signature. The study may be underpowered to validate low-prevalence biomarkers. ConclusionsThe ccB signature was the only independent prognostic biomarker. Enrichment...... of multiple poor prognosis genetic alterations in ccB samples indicated that several events may be required to establish this aggressive phenotype, catalysed in some tumours by chromosomal instability. Multiregion assessment may improve the precision of this biomarker. Patient summaryWe evaluated the ability...

  2. Mesenchymal stem cells and chronic renal artery stenosis.

    Science.gov (United States)

    Oliveira-Sales, Elizabeth B; Boim, Mirian A

    2016-01-01

    Renal artery stenosis is the main cause of renovascular hypertension and results in ischemic nephropathy characterized by inflammation, oxidative stress, microvascular loss, and fibrosis with consequent functional failure. Considering the limited number of strategies that effectively control renovascular hypertension and restore renal function, we propose that cell therapy may be a promising option based on the regenerative and immunosuppressive properties of stem cells. This review addresses the effects of mesenchymal stem cells (MSC) in an experimental animal model of renovascular hypertension known as 2 kidney-1 clip (2K-1C). Significant benefits of MSC treatment have been observed on blood pressure and renal structure of the stenotic kidney. The mechanisms involved are discussed.

  3. Clear-cell chondrosarcoma of the maxilla Report of a case

    NARCIS (Netherlands)

    Slootweg, P.J.

    1980-01-01

    Clear-cell chondrosarcoma is a variant of chondrosarcoma which is characterized by a typical histomorphology and a very slow rate of growth. A case is presented in which the tumor was located in the maxilla.

  4. Renal stem cell reprogramming: Prospects in regenerative medicine

    Institute of Scientific and Technical Information of China (English)

    Elvin; E; Morales; Rebecca; A; Wingert

    2014-01-01

    Stem cell therapy is a promising future enterprise for renal replacement in patients with acute and chronic kidney disease, conditions which affect millions worldwide and currently require patients to undergo lifelong medical treatments through dialysis and/or organ transplant. Reprogramming differentiated renal cells harvested from the patient back into a pluripotent state would decrease the risk of tissue rejection and provide a virtually unlimited supply of cells for regenerative medicine treatments, making it an exciting area of current research in nephrology. Among the major hurdles that need to be overcome before stem cell therapy for the kidney can be applied in a clinical setting are ensuring the fidelity and relative safety of the reprogrammed cells, as well as achieving feasible efficiency in the reprogramming processes that are utilized. Further, improved knowledge about the genetic control of renal lineage development is vital to identifying predictable and efficient reprogramming approaches, such as the expression of key modulators or the regulation of geneactivity through small molecule mimetics. Here, we discuss several recent advances in induced pluripotent stem cell technologies. We also explore strategies that have been successful in renal progenitor generation, and explore what these methods might mean for the development of cell-based regenerative therapies for kidney disease.

  5. Chondroblastoma and clear cell chondrosarcoma: radiological and MRI characteristics with histopathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kaim, Achim H.; Huegli, Rolf [Institute of Diagnostic Radiology, University Hospital Basle (Switzerland); Bonel, Harald M. [Institute of Clinical Radiology, University Hospital, Munich-Grosshadern (Germany); Jundt, Gernot [Institute of Pathology, University Hospital Basle (Switzerland)

    2002-02-01

    Objective: To analyze and compare the radiological and magnetic resonance imaging (MRI) appearances of chondroblastoma and clear cell chondrosarcoma with histopathological correlation. Design and patients: Twelve patients with histologically proven chondroblastoma and of another four patients with clear cell chondrosarcoma were investigated by radiographs and MRI (T1-, T2-weighted sequences, intravenous gadolinium application). Additionally, the clinical and radiologic data of seven cases of clear cell chondrosarcoma without available MRI were considered. The localization, calcification of tumor matrix, periosteal reaction, cortical bone and patterns of bone destruction were analyzed according to the Lodwick radiological grading system (LRGS). The signal intensity on T1- and T2-weighted sequences, characteristics of contrast enhancement, associated bone marrow edema, soft tissue reaction and joint involvement were evaluated. Histopathological specimens were available in all cases. Results: The age of patients with chondroblastoma (range 15-59 years, mean 22.3 years) was lower than that of those with clear cell chondrosarcoma (range 19-61 years, mean 36.6 years), and the lesions were smaller in the chondroblastoma group (range 1-4 cm, mean 2.3 cm) than in patients with clear cell chondrosarcoma (range 3-7.5 cm, mean 5.2 cm). The chondroblastomas were more confined to the epiphysis (10/12) than the clear cell chondrosarcomas. All chondroblastomas and clear cell chondrosarcomas except one were classified as grade 1A or 1B according to the LRGS; one clear cell chondrosarcoma was judged as grade 2. Signal intensity of the tumors on MRI was very heterogeneous in both groups. High signal intensity on T2-weighted MR images in chondroblastoma mostly corresponded to areas with aneurysmal bone cyst components and in clear cell chondrosarcoma to islands of hyaline cartilage. Contrast enhancement occurred in all tumors and tended to be more intense with clear cell

  6. Solar cell process development in the European integrated project CrystalClear

    Energy Technology Data Exchange (ETDEWEB)

    Beaucarne, G.; John, J.; Choulat, P.; Ma, Y. [IMEC vzw, Kapeldreef 75, B-3001 Leuven (Belgium); Russel, R. [BP Solar Espana, Madrid (Spain); Romijn, I.; Weeber, A. [ECN Solar Energy, PO Box 1, NL 1755 ZG Petten (Netherlands); Hofmann, M.; Preu, R. [Fraunhofer Institute for Solar Energy Systems ISE, Heidenhofstr. 2, 79110 Freiburg (Germany); Slaoui, A. [InESS, Strassbourg (France); Le Quang, N.; Nichiporuk, O. [Photowatt Technologies, Bourgoin-Jallieu (France); Del Caoizo, C; Pan, A. [Polytechnical University of Madrid, Madrid (Spain); Solheim, H.; Evju, J. [REC Scancell, Sandvika (Norway); Nagel, H.; Horzel, J. [SCHOTT Solar, Alzenau (Germany); Bitnar, B.; Heemeier, M.; Weber, T. [SolarWorld, Freiberg/Sachsen (Germany); Raabe, B.; Haverkamp, H.; Struempel, C.; Junge, J.; Riegel, S.; Seren, S.; Hahn, G. [University of Konstanz, Department of Physics, P.O.Box X916, 78457 Konstanz (Germany)

    2008-10-15

    CrystalClear is a large integrated project funded by the European Commission that aims to drastically reduce the cost of crystalline Si PV modules, down to 1 Euro/Wp. Among the different subprojects, the one dealing with the development of advanced solar cells is relatively large (with 11 partners out of the 15 Crystal Clear partners taking part) and has a crucial role. The goal of the subproject is to develop cell design concepts and manufacturing processes that would enable a reduction in the order of 40% of the cell processing costs per Wp. In this paper, we give an overview of all the development work that has taken place in the CrystalClear solar cells subproject so far. World class results have been achieved, particularly on high efficiency cells on Si ribbons, and on industrial-type solar cells on very thin (120 {mu}m thick) substrates.

  7. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

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

  8. Trigeminal perineural spread of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

  9. 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.

  10. Bilateral multiloculated cystic renal cell carcinoma (Case report)

    OpenAIRE

    Gümürdülü, D; Uğuz, A; Gökdemir, A.; Soyupak, B.

    2014-01-01

    Aim: Multiloculated cystic renal cell carcinoma is a rare variant of renal cell carcinoma. Incidence and biological behaviour of the tumor are unknown and bilateral cases are very rare. Case report: Fifty four-years- old male patient was admitted to the Urology policlinic with a left flank pain which was present during one month. On ultra sonographic examination solid hypoecoic mass 37x 32 mm in size and extending to the adrenal area were found at the upperpole of right kidney. Another mass 3...

  11. Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors.

    Science.gov (United States)

    Nagle, Christina M; Olsen, Catherine M; Webb, Penelope M; Jordan, Susan J; Whiteman, David C; Green, Adèle C

    2008-11-01

    Endometrioid and clear cell subtypes of ovarian cancer are both known to be closely associated with endometriosis and endometrial pathology, and so have often been combined in studies of causation. We have examined these ovarian cancers separately for potentially distinct risk factors in our population-based, Australia-wide case control study of 142 women with incident invasive endometrioid, 90 with clear cell ovarian cancers and 1508 population controls. Multivariate logistic regression was used to calculated odds ratios (ORs) and 95% confidence intervals (CIs). Increasing parity, and hormonal contraceptive use for > or = 5 years, strongly decreased the risks of both subtypes. Breast feeding and tubal ligation were also inversely associated, but significantly so only for the endometrioid subtype. As expected endometriosis increased the risk of both subtypes (OR 2.2, 95% CI 1.2-3.9 for endometrioid and OR 3.0, 95% CI 1.5-5.9 for clear cell). Obesity was associated only with clear cell cancers, where we observed a two-fold increased risk (OR 2.2, 95% CI 1.2-4.1). Also a significant trend of decreasing risk with increasing intensity of smoking (p trend 0.02) and education beyond high school was associated with decreased development of clear cell cancers only. Endometrioid and clear cell ovarian cancers have some shared as well as some distinct risk factors, and therefore should be considered separately in studies of ovarian cancer. PMID:18707869

  12. Regulatory T cells in immune-mediated renal disease.

    Science.gov (United States)

    Ghali, Joanna R; Wang, Yuan Min; Holdsworth, Stephen R; Kitching, A Richard

    2016-02-01

    Regulatory T cells (Tregs) are CD4+ T cells that can suppress immune responses by effector T cells, B cells and innate immune cells. This review discusses the role that Tregs play in murine models of immune-mediated renal diseases and acute kidney injury and in human autoimmune kidney disease (such as systemic lupus erythematosus, anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated vasculitis). Current research suggests that Tregs may be reduced in number and/or have impaired regulatory function in these diseases. Tregs possess several mechanisms by which they can limit renal and systemic inflammatory immune responses. Potential therapeutic applications involving Tregs include in vivo induction of Tregs or inducing Tregs from naïve CD4+ T cells or expanding natural Tregs ex vivo, to use as a cellular therapy. At present, the optimal method of generating a phenotypically stable pool of Tregs with long-lasting suppressive effects is not established, but human studies in renal transplantation are underway exploring the therapeutic potential of Tregs as a cellular therapy, and if successful may have a role as a novel therapy in immune-mediated renal diseases. PMID:26206106

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

    Directory of Open Access Journals (Sweden)

    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

  14. Malignant renal tumors in children

    Directory of Open Access Journals (Sweden)

    Justin Scott Lee

    2015-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-15

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

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

    International Nuclear Information System (INIS)

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

  17. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  18. Validity of positron emission tomography (PET) using 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (FDG) in patients with renal cell carcinoma (preliminari report)

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Juichi; Hida, Shuichi; Yoshida, Osamu; Yonekura, Yoshiharu; Senda, Michio; Yamamoto, Kazutaka; Saji, Hideo; Fujita, Toru; Konishi, Junji.

    1988-10-01

    Positron emission tomography (PET) using 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (FDG) was carried out in 6 patients with renal tumors (5 renal cell carcinomas including one patient in whom the primary renal lesion was nephrectomized and 1 angiomyolipoma) and FDG accumulation was evaluated in the tumor lesion as a ''hot spot''. In dynamic images after 16 min. FDG accumulated in the tumor portion in 3 out of 4 patients with renal cell carcinoma. However, there was no accumulation in one renal cell carcinoma in which marked necrosis was histologically found. FDG accumulation was not evident in the tumorous lesion of angiomyolipoma. FDG accumulation was also noticed in the metastatic lesion of renal cell carcinoma in the liver or retroperitoneal lymph node. A gradual increase of FDG activity in the lesion of renal cell carcinoma was clearly demonstrated in the time-radioactivity curve, while activities rapidly decreased in renal cortex and pelvis, and liver. In the healthy portion of the kidney, FDG is filtered from the glomerulus and is not reabsorbed from the tubulus and is excreted in the collecting system. On the contrary, FDG, catalyzed by hexokinase, is phospholylated to FDG-6-phosphate which accumulates in the tumor tissue. PET using FDG can provide a new insight for understanding biological activity of renal cell carcinoma from the point of glucose metabolism in tumor tissue.

  19. On-chip clearing of arrays of 3-D cell cultures and micro-tissues.

    Science.gov (United States)

    Grist, S M; Nasseri, S S; Poon, T; Roskelley, C; Cheung, K C

    2016-07-01

    Three-dimensional (3-D) cell cultures are beneficial models for mimicking the complexities of in vivo tissues, especially in tumour studies where transport limitations can complicate response to cancer drugs. 3-D optical microscopy techniques are less involved than traditional embedding and sectioning, but are impeded by optical scattering properties of the tissues. Confocal and even two-photon microscopy limit sample imaging to approximately 100-200 μm depth, which is insufficient to image hypoxic spheroid cores. Optical clearing methods have permitted high-depth imaging of tissues without physical sectioning, but they are difficult to implement for smaller 3-D cultures due to sample loss in solution exchange. In this work, we demonstrate a microfluidic platform for high-throughput on-chip optical clearing of breast cancer spheroids using the SeeDB, Clear(T2), and ScaleSQ clearing methods. Although all three methods are able to effectively clear the spheroids, we find that SeeDB and ScaleSQ more effectively clear the sample than Clear(T2); however, SeeDB induces green autofluorescence while ScaleS causes sample expansion. Our unique on-chip implementation permits clearing arrays of 3-D cultures using perfusion while monitoring the 3-D cultures throughout the process, enabling visualization of the clearing endpoint as well as monitoring of transient changes that could induce image artefacts. Our microfluidic device is compatible with on-chip 3-D cell culture, permitting the use of on-chip clearing at the endpoint after monitoring the same spheroids during their culture. This on-chip method has the potential to improve readout from 3-D cultures, facilitating their use in cell-based assays for high-content drug screening and other applications. PMID:27493703

  20. Renal Cell Carcinoma Mimicking Adrenal Tumor

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Moslemi

    2010-01-01

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

  1. 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.

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

    OpenAIRE

    Hoti Lal; Shameer; Manish; Sadasukhi

    2015-01-01

    Primary Squamous Cell Carcinoma in the kidney is a rare malignant neoplasm associated with nephrolithiasis, typically monobacterial pyonephrosis and rarely Xanthogranulomatous pyelonephritis. It is an aggressive disease with a poor prognosis mostly due to lack of presenting clinical features like a palpable mass, gross haematuria and pain. We report a case presenting with renal calculus and pyonephrosis managed initially with percutaneous nephrostomy followed by nephrectomy du...

  3. Case of clear cell ependymoma of medulla oblongata: clinicopathological and immunohistochemical study with literature review.

    Science.gov (United States)

    Amatya, Vishwa Jeet; Takeshima, Yukio; Kaneko, Mayumi; Nakano, Tomohiro; Yamaguchi, Satoshi; Sugiyama, Kazuhiko; Kurisu, Kaoru; Nakazato, Yoichi; Inai, Kouki

    2003-05-01

    Clear cell ependymoma has been included in the WHO classification of the central nervous system in 1993, after the first report by Kawano et al. Since then, only a few cases have been reported. Most clear cell ependymoma cases reported in the literature so far were located in the supra-tentorial compartment and/or cerebellum, and one case was in the cervical spinal cord. We report a case of clear cell ependymoma whose histological features were sufficient for the diagnosis and was unusually located in the fourth ventricle originating from the medulla oblongata. The tumor showed uniform tumor cells with perinuclear halo, nuclei being centrally located. Most of the tumor cells were arranged as perivascular pseudorosettes, and no ependymal canals or rosettes were evident. Mitotic figures were not frequent. Immunohistochemically, the tumor cells were strongly reactive for glial fibrillary acidic protein and vimentin, and weak and dot-like positive for epithelial membrane antigen. Clear cell change of the tumor cells appeared to be fixation artifact because this feature was not evident in the frozen section. PMID:12713564

  4. 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

  5. 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.

  6. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    International Nuclear Information System (INIS)

    Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively. The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses

  7. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    Directory of Open Access Journals (Sweden)

    Oliveira Jorge

    2007-07-01

    Full Text Available Abstract Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC, 13 papillary (pRCC, 10 chromophobe (chRCC, and 10 oncocytomas and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007, PTGS2 (p = 0.002, and RASSF1A (p = 0.0001. CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively, whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004. RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035. In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031 and nuclear grade (p = 0.022, respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

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

    Directory of Open Access Journals (Sweden)

    Shouki Bazarbashi

    2011-01-01

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

  9. 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

  10. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

    Directory of Open Access Journals (Sweden)

    Verzoni E

    2014-03-01

    Full Text Available Elena Verzoni, Paolo Grassi, Isabella Testa, Roberto Iacovelli, Pamela Biondani, Enrico Garanzini , Filippo De Braud, Giuseppe ProcopioDepartment of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials.Keywords: axitinib, renal cell carcinoma, vascular endothelial growth factor receptor, angiogenesis

  11. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Todenhöfer Tilman

    2012-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Alvaro C Ucero

    2010-04-01

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

  13. Alcoholic beverages and risk of renal cell cancer

    NARCIS (Netherlands)

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

    2007-01-01

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

  14. [Three Patients with Acute Myocardial Infarction Associated with Targeted Therapy of Sorafenib for Metastatic Renal Cell Carcinoma : Case Report].

    Science.gov (United States)

    Takagi, Kimiaki; Takai, Manabu; Kawata, Kei; Horie, Kengo; Kikuchi, Mina; Kato, Taku; Mizutani, Kosuke; Seike, Kensaku; Tsuchiya, Tomohiro; Yasuda, Mitsuru; Yokoi, Shigeaki; Nakano, Masahiro; Ushikoshi, Hiroaki; Miyazaki, Tatsuhiko; Deguchi, Takashi

    2015-09-01

    Sorafenib is a tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor receptor (VEGFR) used for advanced renal cell carcinoma. Treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal cell carcinoma. However, in spite of its therapeutic efficacy, sorafenib causes a wide range of adverse events. Cardiovascular adverse events have been observed when sorafenib was used with targeted agents. Although these adverse events like hypertension, reduced left ventricular ejection fraction, cardiac ischemia or infarction were manageable with standard medical therapies in most cases, some had a poor clinical outcome. We report three cases of acute myocardial infarction associated with sorafenib in patients with metastatic renal cell carcinoma.

  15. 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.

  16. Collision tumor of the kidney composed of clear cell carcinoma and collecting duct carcinoma:report of a case with unusual morphology and clinical follow-up

    Institute of Scientific and Technical Information of China (English)

    Rhonda Burch-Smith; Nizar M Tannir; Erika Resetkova; Pheroze Tamboli; Priya Rao

    2014-01-01

    We report the case of a 67-year-old female who presented with a large renal mass. Gross examination of the nephrectomy specimen demonstrated a 6-cm renal mass that invaded into the renal sinus and perinephric fat. Histologic examination revealed two distinct tumor types. The first type was a conventional (clear cell) renal cell carcinoma that was of low nuclear grade and comprised the minority of the overall tumor. The second type was a high-grade collecting duct carcinoma with glandular/tubular differentiation and composed the majority of the tumor. Immunohistochemical studies demonstrated distinctive patterns of the two tumor types, thus confirming two distinct lineages. Five months postoperatively, the patient developed metastasis to the lungs and right hilar lymph node region. A fine needle aspiration of a lung nodule demonstrated a metastatic, poorly differentiated carcinoma, similar to the colecting duct carcinoma component in the kidney. Colision tumors of the kidney are rare with fewer than 10 cases reported in the literature. Our report further expands the spectrum of this rare phenomenon.

  17. 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...

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

    Science.gov (United States)

    The National Cancer Institute’s Urologic Oncology Branch seeks parties to co-develop the UOK 262 immortalized cell line as research tool to study aggressive hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated recurring kidney cancer.

  19. Imaging Nuclear Morphology and Organization in Cleared Plant Tissues Treated with Cell Cycle Inhibitors.

    Science.gov (United States)

    de Souza Junior, José Dijair Antonino; de Sa, Maria Fatima Grossi; Engler, Gilbert; Engler, Janice de Almeida

    2016-01-01

    Synchronization of root cells through chemical treatment can generate a large number of cells blocked in specific cell cycle phases. In plants, this approach can be employed for cell suspension cultures and plant seedlings. To identify plant cells in the course of the cell cycle, especially during mitosis in meristematic tissues, chemical inhibitors can be used to block cell cycle progression. Herein, we present a simplified and easy-to-apply protocol to visualize mitotic figures, nuclei morphology, and organization in whole Arabidopsis root apexes. The procedure is based on tissue clearing, and fluorescent staining of nuclear DNA with DAPI. The protocol allows carrying out bulk analysis of nuclei and cell cycle phases in root cells and will be valuable to investigate mutants like overexpressing lines of genes disturbing the plant cell cycle.

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

    Science.gov (United States)

    Freedman, Benjamin S; Steinman, Theodore I

    2015-08-01

    iPS cells from patients with kidney disease are a new tool with the potential to impact the future of renal care. They can be used in the laboratory to model the pathophysiology of human kidney disease, and have the potential to establish a new area of immunocompatible, on-demand renal transplantation. Critical challenges remain before the full potential of these cells can be accurately assessed. We need to understand whether the derived cell types are mature and can replace kidney function(s). To what extent can iPS cells model kidney disease in the simplified environment of cell culture? Ultimately, successful integration of these cells as autograft therapies will require demonstration of safety and efficacy equal or superior to the existing gold standards of kidney allograft transplantation and dialysis. Specific educational and infrastructural changes will be necessary if these specialized technologies are to be adopted as an accepted modalities in clinical medicine. Given these barriers, the first fruit of these labors is likely to be improved understanding of pathophysiological pathways in human IPS cell disease models, followed by drug discovery and testing. These experiments will lead naturally to improvements in differentiation and experiments in animal models testing function. The time course to achieve the desired goals remains unknown, but the ultimate hope is that new, more effective and less expensive modalities for renal replacement therapy will occur in the foreseeable future. A new standard of care for patients is anticipated that addresses limitations of currently available treatments. PMID:26454909

  1. Synchronous Bilateral Adrenal Metastases from Papillary Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kaan Gokcen

    2014-12-01

    Full Text Available We report a case of synchronous bilateral adrenal metastasis of renal cell carcinoma. The contralateral metastatic adrenal mass was treated by the laparoscopic transperitoneal approach. The renal mass and its huge ipsilateral metastatic adrenal gland were removed en bloc with open procedure. A 54-year-old man presented to our clinic with left-sid renal cell carcinoma synchronously bilateral adrenal metastases. The primary tumor was localized in the upper-mid pole of the kidney. The diagnosis was established preoperatively by computed tomography. The size of the contralateral adrenal mass was 65 x 45 mm, but the ipsilateral metastatic adrenal mass was huge (140 x 65 mm. After all analysis and other scannings for any metastasis, a contralateral lapararoscopic transperitoneal adrenalectomy and a left open nephroadrenalectomy were performed simultaneously. Synchronous bilateral adrenal metastases from primary renal cell carcinoma without another metastasis is very rare. The optimal surgical procedure should be selected according to the metastatic adrenal masses size and the patient%u2019s status.

  2. Oncogenic micro-RNAs and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cristina eGrange

    2014-03-01

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

  3. Primary clear cell ductal adenocarcinoma of the pancreas: A case report and clinicopathologic literature review

    Directory of Open Access Journals (Sweden)

    Yashpal Modi

    2014-01-01

    Full Text Available We present a very rare, interesting case of a carcinoma of the pancreas with predominantly abundant clear cell morphology. According to the WHO classification, primary clear cell carcinoma of the pancreas is classified as a rare "miscellaneous" carcinoma. The tumor was observed in the distal body and tail of the pancreas of a 74-year-old woman. The histopathology of tumor cells showed well-defined cell membranes, clear cytoplasm, and prominent cell boundaries. Immunohistochemical (IHC staining showed positive reactions to antibodies against vimentin, cytokeratin 7 (CK-7, mucicarmine (MUC-1, periodic acid-Schiff (PAS, periodic acid-Schiff with diastase (PASD, carcinoembryonic antigen (CEA, and Carbohydrate Antigen 19-9 (CA 19-9. On the other hand, IHC staining was negative for alpha-fetoprotein (AFP, cytokeratin 20 (CK-20, HMB45, chromogranin, and synaptophysin. The patient was subsequently diagnosed with a primary solid-type pancreatic clear cell carcinoma with hepatic metastasis. Herein, we report this rare case and include a review of the current literature of this tumor.

  4. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

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

    2015-01-01

    to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily......-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.)....

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

    Directory of Open Access Journals (Sweden)

    Chen C

    2003-01-01

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

  6. Renal (Kidney) Manifestations in TSC

    Medline Plus

    Full Text Available ... in TSC: renal cysts, renal angiomyolipoma and renal cell carcinoma . Renal angiomyolipomata, or angiomyolipomas, are usually the ... kidney failure, requiring dialysis or transplantation. Lastly, renal cell carcinoma, the least common renal association with TSC, ...

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

    Directory of Open Access Journals (Sweden)

    Chiara Paglino

    2011-12-01

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

  8. Review series: The cell biology of renal filtration.

    Science.gov (United States)

    Scott, Rizaldy P; Quaggin, Susan E

    2015-04-27

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

  9. 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.

  10. Clear cell myoepithelioma of palate with emphasis on clinical and histological differential diagnosis.

    Science.gov (United States)

    Nair, Bindu J; Vivek, Velayudhannair; Sivakumar, Trivandrum T; Joseph, Anna P; Varun, Babyamma Raghavanpillai; Mony, Vinod

    2014-03-27

    Myoepitheliomas account for less than 1% of all salivary gland tumors and mostly occur in the parotid gland and palate. A 58-year old male patient reported to the Outpatient Department of PMS College of Dental Science and Research (Kerala, India) with a slow growing painless swelling on the palate for 4 years. Pleomorphic adenoma, basal cell adenoma, myoepithelioma, cyst adenoma, lipoma, neurofibroma, neurilemmoma and leiomyoma were considered. Histopathology revealed a thinly encapsulated tumor composed mainly of sheets of clear cells mixed with cells having eosinophilic cytoplasm. Histopathological differential diagnosis included pleomorphic adenoma, oncocytoma, oncocytic hyperplasia, sebaceous adenoma, malignant salivary gland neoplasms and metastatic lesions from kidney and thyroid. Myoepitheliomas mostly occur in the parotid gland and palatal region and various histological types of myoepithelioma are described. Myoepitheliomas of the palate are rare with clear cell variant even rarer.

  11. Boron neutron capture therapy as new treatment for clear cell sarcoma: Trial on different animal model

    International Nuclear Information System (INIS)

    Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. - Highlights: • BNCT with the use of L-BPA was applied for three human clear cell sarcoma (CCS) cell lines. • BNCT trial was performed on a newly established intramuscularly CCS-bearing animal model. • A significant decrease of the tumor-volume was seen by single BNCT with the use of L-BPA. • A multiple BNCT application would be required for controlling the growth of any residual tumors

  12. 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...

  13. [1-{sup 11}C]Acetate uptake is not increased in renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kotzerke, J.; Beuthien-Baumann, B. [Technische Universitaet Dresden und PET Zentrum Rossendorf, Klinik und Poliklinik fuer Nuklearmedizin, Dresden (Germany); Linne, C.; Wirth, M. [Technische Universitaet Dresden, Klinik und Poliklinik fuer Urologie, Dresden (Germany); Meinhardt, M.; Baretton, G. [Technische Universitaet Dresden, Institut fuer Pathologie, Dresden (Germany); Steinbach, J. [PET Zentrum Rossendorf, Forschungszentrum Rossendorf, Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Dresden (Germany); Abolmaali, N. [Technische Universitaet Dresden, OncoRay, Medizinische Fakultaet Carl Gustav Carus, Dresden (Germany)

    2007-06-15

    The purpose of this study was to investigate the potential of [1-{sup 11}C]acetate (AC) as a metabolic tracer for renal cell cancer in human subjects. Twenty-one patients with suspected kidney tumours were investigated with AC and dynamic PET. AC uptake was scored on a five-step scale. Tumour localisation was known from CT/MRI. Histology was available in 18/21 patients. The results in these 18 patients are reported. AC uptake by the tumour was less than (n = 11), equal to (n = 5) or higher than (n = 2) uptake in the surrounding renal parenchyma. Histological tumour types showed a typical distribution, with a predominance of clear cell carcinomas (n = 14) and only a small number of papillary cell carcinomas (n = 2) and oncocytomas (n = 2). Only the benign oncocytomas were highly positive with AC. In most kidney tumours the AC accumulation was not higher than in normal kidney parenchyma. Therefore, AC PET cannot be recommend for the characterisation of a renal mass. (orig.)

  14. 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.

  15. Telomere length in relation to immunological parameters in patients with renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Ulrika Svenson

    Full Text Available Over the last decade, telomere length (TL has gained attention as a potential biomarker in cancer disease. We previously reported that long blood TL was associated with a poorer outcome in patients with breast cancer and renal cell carcinoma. Based on these findings, we hypothesized that certain immunological components may have an impact on TL dynamics in cancer patients. One aim of the present study was to investigate a possible association between serum cytokines and TL of peripheral blood cells, tumors and corresponding kidney cortex, in patients with clear cell renal cell carcinoma. For this purpose, a multiplex cytokine assay was used. Correlation analysis revealed significant positive correlations between tumor TL and peripheral levels of three cytokines (IL-7, IL-8 and IL-10. In a parallel patient group with various kidney tumors, TL was investigated in whole blood and in immune cell subsets in relation to peripheral levels of regulatory T cells (Tregs. A significant positive association was found between whole blood TL and Treg levels. However, the strongest correlation was found between Tregs and TL of the T lymphocyte fraction. Thus, patients with higher Treg levels displayed longer T cell telomeres, which might reflect a suppressed immune system with fewer cell divisions and hence less telomere shortening. These results are in line with our earlier observation that long blood TL is an unfavorable prognostic factor for cancer-specific survival. In summary, we here show that immunological components are associated with TL in patients with renal cell carcinoma, providing further insight into the field of telomere biology in cancer.

  16. Participation of functionally active plasma cells in acute rejection and response to therapy in renal allografts.

    Science.gov (United States)

    Bhat, Zeenat Yousuf; Bostwick, David G; Hossain, Deloar; Zeng, Xu

    2014-07-01

    Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection. The inflammatory infiltrate comprised not only T cells but also varying amounts of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with poor clinical outcomes, but their functional status is not clear. The phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are metabolically active, thus identifying functionally active antibody-secreting plasma cells. This study was designed to evaluate the clinical significance of functionally active p-S6RP plasma cells in AR in renal allografts. Renal allografts with biopsy evidence of AR during 2006-2009 were included. Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on paraffin-embedded slides and scaled as 0-6. The response to antirejection treatment was assessed by the serum creatinine ratio (CrR) at rejection episode (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0-2) were compared with a higher scored group (3-6). The T-test was conducted using statistical significance of p<0.05. A total of 28 patients (40.7 ± 14.3 year; M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p-S6RP staining in the high-score group had a significantly higher CrR (p<0.05) than the low-score group at the time of biopsy, 4 and 12 weeks following treatment. There was no significant difference in the CrR between groups for CD20 or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively participating in AR and associated with poor response to treatment in renal allografts. PMID:24684655

  17. 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.

  18. Lung adenocarcinoma with clear cell features producing carbohydrate antigen 19-9.

    Science.gov (United States)

    Goto, Taichiro; Hada, Masao; Oyama, Toshio

    2015-10-01

    A 76-year-old man underwent surgery for lung cancer. Histopathologically, most of the resected tumor was composed of polygonal cells with foamy cytoplasm, and the cells were arranged predominantly in acinar patterns. In this case, although the carbohydrate antigen 19-9 level was high before surgery, it normalized after resection. The tumor was considered a carbohydrate antigen 19-9-producing tumor, which was further supported by the results of immunohistochemical analysis. Adenocarcinoma with clear cell features, producing carbohydrate antigen 19-9, is an exceedingly rare entity.

  19. 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.

  20. Surgical Treatment of Pancreatic Metastases of Renal Cell Carcinoma

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    Molmenti E

    2005-07-01

    Full Text Available CONTEXT: The pancreas is an unusual site for metastases of renal cell carcinoma origin, sometimes occurring many years after nephrectomy. We herein present two cases of pancreatic metastases of renal cell carcinoma which occurred 17 and 19 years after the primary diagnosis. CASE REPORT: In the first case, metastases were found in the head of the pancreas, upper right arm and the right lobe of the thyroid gland. In the second case, a tumor was found in the tail of the pancreas and a remnant of the right kidney. This was the third recurrence of the original tumor after an initial left nephrectomy and two subsequent partial right nephrectomies in the past. Treatment in the first case consisted of excision of the tumor in the upper right arm, a Whipple operation, and a thyroidectomy. In the second case, a distal pancreatectomy and remnant right nephrectomy were undertaken. Both patients recovered from the operations without complications and remain free of tumor in follow-up periods of 54 and 8 months respectively. CONCLUSIONS: Resection of renal cell carcinoma metastases involving the pancreas provides satisfactory long-term survival, and should be undertaken whenever possible.

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

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    Juan Manuel Senior Sánchez

    2006-01-01

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

  2. Mixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Spindle Cell and Clear Cell Features in the Extrahepatic Bile Duct

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    John Wysocki

    2014-01-01

    Full Text Available Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the common hepatic duct. A bile duct excision was performed. Gross examination revealed a 3.6 cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC. Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bile duct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient’s poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas.

  3. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Clear Cell Adenocarcinoma of the Colon: A Case Report and Review of the Literature

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    Christian Daniel Barrera-Maldonado

    2014-01-01

    Full Text Available Clear cell adenocarcinoma of the colon has been described scarcely in the literature. It affects elderly men more commonly than women and usually appears in the left side of the colon. A Hispanic 41-year-old female came to the emergency room with abdominal pain, vomiting, and distension. Physical exam revealed generalized tenderness without peritoneal signs. Laboratory data was unremarkable. A CT scan showed an apple-core lesion in the distal colon. A flexible sigmoidoscopy revealed an obstructive mass that made further evaluation impossible. Exploratory surgery revealed a hard mass obstructing the descending colon, which was resected. Histopathology analysis with immunohistochemistry staining was positive for cytokeratin 20, cytokeratin 10, CDX2, and villin, while it was negative for cytokeratin 7, RCC, vimentin, and CD31. These results confirmed the clear cell variant of the adenocarcinoma. Clear cell adenocarcinomas usually arise from the kidneys and Müllerian organs. Immunohistochemistry is crucial for establishing the origin of these neoplastic cells. A cytokeratin 20+/7− with positive CDX2 is highly specific and sensitive for intestinal neoplastic origin. The main treatment has been surgery alone with moderately good results. More research and information about this malignancy is needed, especially in regard to prognosis and in order to provide the best treatment option.

  6. Autophagy Inhibition to Augment mTOR Inhibition: A Phase I/II Trial of RAD001 and Hydroxychloroquine in Patients With Previously Treated Renal Cell Carcinoma

    Science.gov (United States)

    2015-12-07

    Histological Evidence of Metastatic Clear Cell Renal Cell Carcinoma; That Has Been Previously Treated With 1-3 Prior Regimens. Phase 1 Only, Any Number of Prior Regimens; With Evidence of Progressive Disease on or Within 6 Months; of Discontinuing Sunitinib, Sorafenib or Pazopanib. Previous; Therapy With Bevacizumab, IL2, or Interferon Are Permitted.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-11-15

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

  8. Selective cytotoxicity of indirect nonequilibrium atmospheric pressure plasma against ovarian clear-cell carcinoma.

    Science.gov (United States)

    Utsumi, Fumi; Kajiyama, Hiroaki; Nakamura, Kae; Tanaka, Hiromasa; Hori, Masaru; Kikkawa, Fumitaka

    2014-01-01

    Ovarian clear cell carcinoma (CCC) is a histological type of epithelial ovarian cancer that is less responsive to chemotherapy and associated with a poorer prognosis than serous and endometrioid carcinoma. Non-thermal atmospheric pressure plasma which produces reactive species has recently led to an explosion of research in plasma medicine. Plasma treatment can be applied to cancer treatment to induce apoptosis and tumor growth arrest. Furthermore, recent studies have shown that a medium exposed to plasma also has an anti-proliferative effect against cancer in the absence of direct exposure to plasma. In this study, we confirmed whether this indirect plasma has an anti-tumor effect against CCC, and investigated whether this efficacy is selective for cancer cells. Non-thermal atmospheric pressure plasma induced apoptosis in CCC cells, while human peritoneal mesothelial cells remained viable. Non-thermal atmospheric pressure plasma exhibits selective cytotoxicity against CCC cells which are resistant to chemotherapy.

  9. 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

  10. Post-radiotherapy locoregional recurrence of hyalinizing clear cell carcinoma of palate

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    Sonia Gon

    2013-01-01

    Full Text Available Clear cell carcinoma of the salivary glands is a rare tumor that represents less than 1% of all salivary tumors and is a new disease that is only recognized in recent years. It is rare and the standard treatment is still under investigation. This tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy. Recurrence of the hyalinizing clear cell carcinoma (HCCC after complete surgical resection is uncommonly documented. We hereby report a case of post-radiotherapy locoregional recurrence of HCCC of the palate and recommend further clinicopathological study and long-term follow-up to document the biological behavior of this entity along with highlighting the role of special stains and immunohistochemistry in its diagnosis.

  11. Losartan attenuates renal interstitial fibrosis and tubular cell apoptosis in a rat model of obstructive nephropathy.

    Science.gov (United States)

    He, Ping; Li, Detian; Zhang, Beiru

    2014-08-01

    Ureteral obstruction leads to renal injury and progresses to irreversible renal fibrosis, with tubular cell atrophy and apoptosis. There is conflicting evidence concerning whether losartan (an angiotensin II type I receptor antagonist) mitigates renal interstitial fibrosis and renal tubular epithelial cell apoptosis following unilateral ureteral obstruction (UUO) in animal models. The aim of this study was to investigate the effect and mechanism of losartan on renal tubular cell apoptosis and renal fibrosis in a rat model of UUO. The rats were subjected to UUO by ureteral ligation and were treated with dimethyl sulfoxide (control) or losartan. The controls underwent sham surgery. The renal tissues were collected 3, 5, 7 and 14 days after surgery for measurement of various indicators of renal fibrosis. UUO increased the expression levels of α‑smooth muscle actin and collagen I, and the extent of renal tubular fibrosis and apoptosis in a time‑dependent manner. Losartan treatment partially attenuated these responses. Progression of renal interstitial fibrosis was accompanied by phosphorylation of signal transducer and activator of transcription 3 (STAT3) and altered the expression levels of two apoptosis‑related proteins (Bax and Bcl2). Losartan treatment also partially attenuated these responses. The results indicated that losartan attenuated renal fibrosis and renal tubular cell apoptosis in a rat model of UUO. This effect appeared to be mediated by partial blockage of STAT3 phosphorylation.

  12. Cardiac Metastases of Renal Cell Carcinoma Revealed by Syncope: Diagnosis and Treatment

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    Aziz Bazine

    2014-08-01

    Full Text Available Introduction: Cardiac metastases from renal cell carcinoma are very rare. In this report, we describe a case of ventricular metastases in the absence of vena cava or right atrial involvement. Case Report: We report the case of a 60-year-old man who had a past history of heavy tobacco intake and well-controlled arterial hypertension. He experienced sudden-onset palpitations, lost consciousness and, as a result, was involved in an accident on the public highway. Cardiac arrhythmia was suspected and, therefore, transthoracic echocardiography was suggested, which revealed a large right ventricular mass. Chest and abdominal computed tomography demonstrated a mass in the right ventricle, but without contiguous vena cava involvement, and a right renal mass related to the probable neoplasm. An ultrasound-guided renal biopsy showed a clear-cell renal cell carcinoma. A bone scan revealed a metastatic bone disease. The patient was started on sunitinib treatment, which was well tolerated. However, approximately 8 months later, reevaluation showed pulmonary metastases. The patient was subsequently started on treatment with everolimus, which, however, was poorly tolerated. Two months later, the patient died due to terminal respiratory insufficiency. Discussion: Based on the literature and our observations in this case, targeted antiangiogenic therapy should be considered as a viable therapeutic alternative to metastasectomy for patients with inoperable cardiac metastatic disease as long as there is no baseline systolic or diastolic dysfunction. The case also emphasizes the importance of a thorough history review and physical examination in the workup of patients with syncope.

  13. Cutaneous Epithelioid Clear Cells Angiosarcoma in a Young Woman with Congenital Lymphedema

    OpenAIRE

    Flore Tabareau-Delalande; Anne De Muret; Elodie Miquelestorena-Standley; Anne-Valérie Decouvelaere; Gonzague De Pinieux

    2013-01-01

    Angiosarcomas are rare aggressive neoplasms that can occur secondary to chronic lymphedema (Stewart-Treves syndrome). Although secondary angiosarcomas are commonly described after-mastectomy and/or after-radiotherapy, few cases have been reported in association with chronic lymphedema of congenital origin. We report the clinical, pathological, and cytogenetic findings in a case of cutaneous epithelioid clear cells angiosarcoma that occurred in a 21-year-old woman with hemibody congenital lymp...

  14. CLEAR CELL CARCINOMA WITH COEXISTENT SMALL MUCINOUS TUMOR COMPONENT ARISING FROM EXTRAGONADAL ENDOMETRIOTIC CYST

    OpenAIRE

    Shankar; Aravinth

    2015-01-01

    The occurrence of clear cell carcinoma in extra gonadal endometriotic cyst is well documented in literature. We report a rare case of malignant tumor identified in the mural nodule of a cystic mass. The cyst was located in the retroperitoneum, posterior to caecum. The tumor had an unusual histomorphologic appearance with co - existent minor benign mucinous tumor component. Rare clinical presentation with unfamiliar histomorphological appearance of this tumor makes it w...

  15. Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells

    OpenAIRE

    Yang, Feng-Qiang; Wang, Ji-Jiao; Yan, Jia-Sheng; Huang, Jian-Hua; Li, Wei; Che, Jian-Ping; Wang, Guang-Chun; Liu, Min; Zheng, Jun-Hua

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the ef...

  16. 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...

  17. An unusual presentation of clear cell odontogenic carcinoma in mandibular anterior region

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    Sindhu M Ganvir

    2014-01-01

    Full Text Available Clear cell odontogenic carcinoma (CCOC is a rare, potentially aggressive odontogenic epithelial tumor with tendency for recurrence. It was first described as a clinicopathological entity in 1985 and to date only 73 cases has been reported in English literature. A case of CCOC in 64-year-old male patient in mandibular anterior region is presented which when recurred in soft tissue 5 years after wide surgical resection of mandible, revealed a biphasic pattern as against monophasic pattern of primary neoplasm and was unusually associated with primary squamous cell carcinoma, suggestive of hybrid tumor.

  18. Regenerative Medicine for the Kidney: Renotropic Factors, Renal Stem/Progenitor Cells, and Stem Cell Therapy

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    Akito Maeshima

    2014-01-01

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

  19. Biology of Metastatic Renal Cell Carcinoma

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    Michele Milella, Alessandra Felici

    2011-01-01

    cell biology and tumor-host interactions may hold the key to future advances in such a complex and challenging disease.

  20. Induced autologous stem cell transplantation for treatment of rabbit renal interstitial fibrosis.

    Directory of Open Access Journals (Sweden)

    Guang-Ping Ruan

    Full Text Available INTRODUCTION: Renal interstitial fibrosis (RIF is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. METHODS: A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP. These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. RESULTS: Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05 were observed in serum creatinine (SCr (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L and blood urea nitrogen (BUN (119 ± 22 µmol/L to 97 ± 13 µmol/L, indicating improvement in renal function. CONCLUSIONS: We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function.

  1. 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.

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

    Science.gov (United States)

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

    2015-04-01

    Higher serum level of p-cresol (PC) in chronic kidney disease (CKD) patients has been linked with CKD progression. The toxic effect of PC on diverse cells has been reported by prior studies, except for renal tubular cells. Both autophagy and apoptosis contribute to renal tubular cell death, yet evidence of its response to PC is limited and their crosstalk is still unclear. Autophagy is an important cellular process involved in toxin-induced cell death. Renal tubular cell death in tubular injury is thought to be one of the key events causing the progression of CKD. Thus, we treated rat (NRK-52E) and human (HRPTEC) renal proximal tubular cells (RPTC) with PC and found the cell proliferation was significantly decreased. Cell apoptosis was significantly increased and accompanied with the activation of autophagy as evidenced by increases in LC3-II, beclin 1 and Atg 4. We also found an increase of p62 by c-Jun activation. p62 accumulation could mediate the activation of caspase 8-dependent cell apoptosis. Conversely, knockdown of p62 by siRNA of p62 had the opposite effect by arresting LC3-II accumulation and promoting increasing cell viability. We conclude that PC triggered autophagic RPTC death via JNK-mediated p62 accumulation and then activated caspase 8-dependent cell death pathway. PC can be considered as one of the key events causing progression of CKD, which might affect drug disposition in CKD cases. PMID:25668154

  3. Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib.

    Science.gov (United States)

    Miller, Rowan E; Brough, Rachel; Bajrami, Ilirjana; Williamson, Chris T; McDade, Simon; Campbell, James; Kigozi, Asha; Rafiq, Rumana; Pemberton, Helen; Natrajan, Rachel; Joel, Josephine; Astley, Holly; Mahoney, Claire; Moore, Jonathan D; Torrance, Chris; Gordan, John D; Webber, James T; Levin, Rebecca S; Shokat, Kevan M; Bandyopadhyay, Sourav; Lord, Christopher J; Ashworth, Alan

    2016-07-01

    New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G1-S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. Mol Cancer Ther; 15(7); 1472-84. ©2016 AACR.

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

    Directory of Open Access Journals (Sweden)

    K J Kelly

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

  5. Renal cell carcinoma with metastasis to the submandibular and parotid glands A case report

    NARCIS (Netherlands)

    Smits, J.G.; Slootweg, P.J.

    1984-01-01

    Differential diagnosis between acinic cell carcinoma and renal cell carcinoma is an oft-quoted problem. A case is presented of a 60-year-old woman with metastatic lesions from a renal cell carcinoma to the parotid as well as the submandibular gland. Appropriate diagnosis was delayed due to lack of c

  6. A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation: case report and review of literature

    Science.gov (United States)

    Zhang, Chengsheng; Zhang, Wei; Mu, Dianbin; Shi, Xuetao; Zhao, Lei

    2016-01-01

    An 80-year-old male was referred to our department for a gallbladder mass. He denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis B surface antigen test and antihepatitis C antibody test were found to be negative. Serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64 ng/mL), whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL). Computed tomography scan revealed a solid mass with measurements of 4.6×5.6×7.1 cm, which nearly filled the whole gallbladder space. Radical cholecystectomy, including segments IV B and V of the liver and lymphadenectomy, was performed. The neoplasm in gallbladder was completely resected, and the patient obtained a negative margin. Histological and immunohistochemical profile suggested a clear cell adenocarcinoma of the gallbladder with hepatoid differentiation. After reviewing the literature, we reported that this case is the first identified case of cell adenocarcinoma of the gallbladder with extensive hepatoid differentiation. However, clinical features of clear cell adenocarcinoma with hepatoid differentiation remain unclear due to the extremely rare incidence. There was no indication of adjuvant chemotherapy and no literature has been reported on the application of chemotherapy. This case showed a promising clinical outcome after curative resection, which indicated that surgical treatment could be potentially considered for suitable patients.

  7. Penoscrotal lymphedema associated with metastatic renal cell carcinoma.

    Science.gov (United States)

    Crawley, David; Haddock, Peter; Jackson, Max; Kamradt, Jeffrey; Kesler, Stuart

    2015-08-01

    A 64-year-old male presented with lower back pain, radiating in a sciatic-type distribution, swelling in his lower abdomen and right leg, and edema of the scrotum and penile shaft. A sonogram and CT imaging indicated an enhancing mass in the right kidney and a spinal metastasis. The right lower extremity and penoscrotal lymphedema was caused by lymphatic obstruction due to a sacral metastasis of renal cell carcinoma. He was treated with cytoreductive nephrectomy, radiation and a systemic tyrosine kinase inhibitor. Pelvic imaging is suggested to determine whether malignant lymphatic obstruction is present when presented with idiopathic penoscrotal edema. PMID:26267035

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

    Directory of Open Access Journals (Sweden)

    B. T. Dzumabaeva

    2011-01-01

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

  9. IMMUNOLOGICAL MONITORING OF BIOTHERAPY FOR DISSEMINATED RENAL-CELL CARCINOMA

    OpenAIRE

    O. E. Molchanov; M. I. Karelin

    2009-01-01

    Objective: to assess a role of immunomonitoring in patients with disseminated renal-cell carcinoma.  Subjects and methods. One hundred and seventy-five patients treated in 1998 to 2008 were followed up. The patients received various immunochemotherapy regimens including interleukin-2 (IL-2), interferon-α (IFN-α), Xeloda, cyclophosphamide. The immune status, including lymphocytes and their subpopulations, cytokine components (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12; IFN-α, IFN-γ; tumor necr...

  10. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

    OpenAIRE

    Liou, Victor D.; Darwish, Oussama M.; Henry, Mary M.; Jun, Ik C.; Siddiqui, Sameer A.

    2015-01-01

    Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC) to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC wh...

  11. 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.

  12. The clinical and imaging features of clear cell meningioma in ten cases

    Directory of Open Access Journals (Sweden)

    ZHAO Guang-zuo

    2012-10-01

    Full Text Available Objective To investigate the clinical features and imaging findings of intracranial clear cell meningioma. Methods The clinical data were reviewed, including presentation, imaging and prognosis of 10 patients suffered from intracranial clear cell meningioma for 2 months-7 years and underwent surgical treatment. The patients included five males and five females with the age from nine to sixty-two years old (mean 35.43. The tumors were located at cerebellopontine angle (CPA zone (n = 5, parietal lobe (n = 1, tuberculum sella (n = 1, jugular foramen (n = 1, tentorium of cerebellum (n = 1 or lateral cerebral ventricle (n = 1. The initial symptoms included headache (n = 4, gait disturbance (n = 2, hearing loss (n = 2, vision loss (n = 1 and bucking (n = 1 which were associated with the mass locations. Results CT (n = 8 and MRI (n = 10 of 10 patients were retrospectively reviewed. CT findings of the lesions presented with hyperdensity (n = 6, isodensity (n = 1, or isodensity with hyperdensity (n = 1. MRI T1WI showed isointensity (n = 4, hypointensity with isointensity (n = 4 or hyperintensity (n = 2, whereas T2WI isointensity with hyperintensity (n = 7, presented hypointensity (n = 1, isointensity (n = 1, or hyperintensity (n = 1. On gadolinium-enhanced T1WI, moderate enhancement was seen in 8 lesions and marked enhancement was seen in 2 lesions. In initial CT scanning peritumoral edema was found in 7 cases, dural tail sign in 5 cases, cysts in 7 cases, calcification in 3 cases, periosteal proliferation in 1 case and bone destruction in 5 cases. Seven patients underwent complete resection and 3 underwent subtotal resection. Follow-up period was 11-120 months. Recurrence occurred in 5 patients. The mean recurrence time was 55.62 months. Conclusion Clear cell meningioma is a rare meningioma and often occurs in young persons without significant difference in sex. The CPA zone is the most affected area. The prognosis is closely related to the extent of

  13. Therapy and prognostic features of primary clear cell carcinoma of the liver

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To clarify the therapeutic strategies and prognosis factors of primary clear cell carcinoma of the liver(PCCCL) . METHODS:The clinical pathological data of 64 patients with PCCCL treated with hepatectomy in our hospital from January 2000 to January 2006 were analyzed retrospectively.The patients were divided into two groups to make treatment analysis:curative resection only(n=40) ;and curative resection and postoperative chemotherapy with calcium folinate and tegafur(n= 24) .Meanwhile,the PCCCL patients...

  14. Clear-cell carcinoma of the lung metastatic to the hamate: a case report.

    Science.gov (United States)

    Nissenbaum, M; Kutz, J E; Lister, G D

    1978-01-01

    Metastatic lesions of the hand are uncommon. A report of a solitary metastasis to the hamate seems not to have appeared previously in the literature. A 46-year-old factory worker presented a rare tumor, clear-cell carcinom of the lung, metastasizing to an unusual location, the hamate. The symptoms simulated sympathetic dystrophy and diagnosis was delayed because of the late appearance of radiographic changes over 6 months after symptoms first appeared. Early bone scanning in patients with chronic pain may provide useful information prior to the appearance of X-ray changes.

  15. Clear cell adenocarcinoma of the ulterine cervix in a 15 year old girl: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Joon; Kim, Jee Eun; KIm, Hyung Sik; Choi, Hye Young [Dept. of Radiology, Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2013-10-15

    Cervical cancer is rare in the pediatric population. In cases of cervical cancer, adenocarcinoma is predominantly reported. Clear cell adenocarcinoma (CCAC) of the uterine cervix is a very rare tumor and accounts for only 4% of all adenocarcinomas of the uterine cervix. Risk factors and pathogenesis of this disease are not exactly revealed. The intrauterine exposure to diethylstilbestrol (DES) and associated non-steroidal estrogen during pregnancy before 18 weeks is the only known risk factor. This study reports the imaging finding of primary uterine cervical tumor in a 15-year-old girl, who was finally diagnosed with CCAC, with no maternal history of DES exposure in utero.

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

    Science.gov (United States)

    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.

  17. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

    Science.gov (United States)

    Fadare, Oluwole; Liang, Sharon X

    2012-12-01

    Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear

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

    Directory of Open Access Journals (Sweden)

    Min Su Cheong

    2010-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-15

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

  20. Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

    OpenAIRE

    Kohan Donald E; Schmid Douglas I; Hughes Alisa K

    2002-01-01

    Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx), the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN), h...

  1. Radionuclide imaging of primary renal-cell carcinoma by I-131-labeled antitumor antibody

    International Nuclear Information System (INIS)

    A goat antibody against human renal-cell carcinoma reacted on immunofluorescence with renal-cell carcinomas from 20 patients, but not with normal adult human tissues, including kidney. After i.v. administration the I-131-linked antibody showed preferential tumor localization in six of seven patients with primary renal carcinoma. Labeled antitumor antibodies may have the specificity for tumor imaging that current radiopharmaceuticals lack

  2. Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss

    Directory of Open Access Journals (Sweden)

    Mohammed Mahdi Althaf

    2016-01-01

    Full Text Available The incidence of renal cell carcinomas (RCCs in renal transplant recipients is reported as 1.1-1.5% in the native kidneys and 0.22-0.25% in the renal allograft. There are no data to support routine surveillance for tumors in transplant recipients. Most reported cases of RCCs occurring in renal allografts were incidental findings in asymptomatic patients. Herein, we report the second case of lone chromophobe RCC (ChRCC of the renal allograft presenting with weight loss. Loss of weight is a presenting symptom in one-third of ChRCCs occurring in the native kidneys in the general population. Based on the age of the patient, R.E.N.A.L nephrometry score of the tumor and the lack of data on the prognosis of this histological subtype in a climate of long-term immunosuppression, we elected for radical nephrectomy. We suggest that RCCs should be considered in the differential diagnosis of a transplant recipient presenting with weight loss even in the absence of localizing symptoms or signs.

  3. Chromophobe renal cell carcinoma occurring in the renal allograft of a transplant recipient presenting with weight loss.

    Science.gov (United States)

    Althaf, Mohammed Mahdi; Al-Sunaid, Mohammed S; Abdelsalam, Mohamed Said; Alkorbi, Lutfi A; Al-Hussain, Turki O; Dababo, Mohammed Anas; Haq, Naveed

    2016-01-01

    The incidence of renal cell carcinomas (RCCs) in renal transplant recipients is reported as 1.1-1.5% in the native kidneys and 0.22-0.25% in the renal allograft. There are no data to support routine surveillance for tumors in transplant recipients. Most reported cases of RCCs occurring in renal allografts were incidental findings in asymptomatic patients. Herein, we report the second case of lone chromophobe RCC (ChRCC) of the renal allograft presenting with weight loss. Loss of weight is a presenting symptom in one-third of ChRCCs occurring in the native kidneys in the general population. Based on the age of the patient, R.E.N.A.L nephrometry score of the tumor and the lack of data on the prognosis of this histological subtype in a climate of long-term immunosuppression, we elected for radical nephrectomy. We suggest that RCCs should be considered in the differential diagnosis of a transplant recipient presenting with weight loss even in the absence of localizing symptoms or signs.

  4. 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 ...

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling

    Science.gov (United States)

    Calcagnì, Alessia; kors, Lotte; Verschuren, Eric; De Cegli, Rossella; Zampelli, Nicolina; Nusco, Edoardo; Confalonieri, Stefano; Bertalot, Giovanni; Pece, Salvatore; Settembre, Carmine; Malouf, Gabriel G; Leemans, Jaklien C; de Heer, Emile; Salvatore, Marco; Peters, Dorien JM; Di Fiore, Pier Paolo; Ballabio, Andrea

    2016-01-01

    TFE-fusion renal cell carcinomas (TFE-fusion RCCs) are caused by chromosomal translocations that lead to overexpression of the TFEB and TFE3 genes (Kauffman et al., 2014). The mechanisms leading to kidney tumor development remain uncharacterized and effective therapies are yet to be identified. Hence, the need to model these diseases in an experimental animal system (Kauffman et al., 2014). Here, we show that kidney-specific TFEB overexpression in transgenic mice, resulted in renal clear cells, multi-layered basement membranes, severe cystic pathology, and ultimately papillary carcinomas with hepatic metastases. These features closely recapitulate those observed in both TFEB- and TFE3-mediated human kidney tumors. Analysis of kidney samples revealed transcriptional induction and enhanced signaling of the WNT β-catenin pathway. WNT signaling inhibitors normalized the proliferation rate of primary kidney cells and significantly rescued the disease phenotype in vivo. These data shed new light on the mechanisms underlying TFE-fusion RCCs and suggest a possible therapeutic strategy based on the inhibition of the WNT pathway. DOI: http://dx.doi.org/10.7554/eLife.17047.001

  10. Are clear cell carcinomas of the ovary and endometrium phenotypically identical? A proteomic analysis.

    Science.gov (United States)

    Fata, Cynthia R; Seeley, Erin H; Desouki, Mohamed M; Du, Liping; Gwin, Katja; Hanley, Krisztina Z; Hecht, Jonathan L; Jarboe, Elke A; Liang, Sharon X; Parkash, Vinita; Quick, Charles M; Zheng, Wenxin; Shyr, Yu; Caprioli, Richard M; Fadare, Oluwole

    2015-10-01

    Phenotypic differences between otherwise similar tumors arising from different gynecologic locations may be highly significant in understanding the underlying driver molecular events at each site and may potentially offer insights into differential responses to treatment. In this study, the authors sought to identify and quantify phenotypic differences between ovarian clear cell carcinoma (OCCC) and endometrial clear cell carcinoma (ECCC) using a proteomic approach. Tissue microarrays were constructed from tumor samples of 108 patients (54 ECCCs and 54 OCCCs). Formalin-fixed samples on microarray slides were analyzed by matrix-assisted laser desorption/ionization mass spectrometry, and 730 spectral peaks were generated from the combined data set. A linear mixed-effect model with random intercept was used to generate 93 (12.7%) peaks that were significantly different between OCCCs and ECCCs at the fold cutoffs of 1.5 and 0.667 and an adjusted P value cutoff of 1.0 × 10(-10). Liquid chromatography-tandem mass spectrometry was performed on selected cores from each group, and peptides identified therefrom were compared with lists of statistically significant peaks from the aforementioned linear mixed-effects model to find matches within 0.2 Da. A total of 53 candidate proteins were thus identified as being differentially expressed in OCCCs and ECCCs, 45 (85%) of which were expressed at higher levels in ECCCs than OCCCs. These proteins were functionally diverse and did not highlight a clearly dominant cellular theme or molecular pathway. Although ECCCs and OCCCs are very similar, some phenotypic differences are demonstrable. Additional studies of these differentially expressed proteins may ultimately clarify the significance of these differences. PMID:26243671

  11. 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.

  12. Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall'Oglio

    2005-02-01

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

  13. A case of treatment in a patient with synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands: Clinical observation

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    V. R. Latypov

    2014-01-01

    Full Text Available Synchronous bilateral renal cell carcinoma occurs in 1.4 % of cases. The probability of bilateral adrenal metastases from renal cell carcinoma is less than 0.5 %. The clinical observation presents a case of synchronous bilateral renal cell carcinoma and simultaneous metastatic involvement of both adrenal glands. A 55‑year-old male patient was adm tted with the signs of hematuria and anemia to the Unit of Urology, Clinic of General Surgery, Siberian State Medical University. He was found to have synchronous bilateral renal cell carcinoma and simultaneous bilateral adrenal involvement. Sequential surgical treatment – radical nephrectomy (with adrenal gland removal on the right side and, after 3 months, adrenalectomy and kidney resection on the left side were performed. All the organs removed displayed tumors that proved to be renal cell carcinomas (a clear cell variant. There were lymph node metastases in the right-sided renal portal. Postoperatively, the investigators performed hormone replacement therapy for adrenal insufficiency, an immunotherapy cycle, three cycles of targeted therapy withsorafenib and sunitinib (at an interval of 0.5–2 years, and insulin therapy for new-onset diabetes mellitus. The duration of a follow-up was 6.2 years. When describing the case, the patient was alive and showed a generalized tumorous process with extensive tumor involvement of the solitary kidney. Sunitinib therapy was used.

  14. 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

  15. 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

  16. 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.

  17. Transduction of interleukin-10 through renal artery attenuates vascular neointimal proliferation and infiltration of immune cells in rat renal allograft.

    Science.gov (United States)

    Xie, Jingxin; Li, Xueyi; Meng, Dan; Liang, Qiujuan; Wang, Xinhong; Wang, Li; Wang, Rui; Xiang, Meng; Chen, Sifeng

    2016-08-01

    Renal transplantation is the treatment of choice for end-stage renal failure. Although acute rejection is not a major issue anymore, chronic rejection, especially vascular rejection, is still a major factor that might lead to allograft dysfunction on the long term. The role of the local immune-regulating cytokine interleukin-10 (IL-10) in chronic renal allograft is unclear. Many clinical observations showed that local IL-10 level was negatively related to kidney allograft function. It is unknown this negative relationship was the result of immunostimulatory property or insufficient immunosuppression property of local IL-10. We performed ex vivo transduction before transplantation through artery of the renal allograft using adeno-associated viral vectors carrying IL-10 gene. Twelve weeks after transplantation, we found intrarenal IL-10 gene transduction significantly inhibited arterial neointimal proliferation, the number of occluded intrarenal artery, interstitial fibrosis, peritubular capillary congestion and glomerular inflammation in renal allografts compared to control allografts receiving PBS or vectors carrying YFP. IL-10 transduction increased serum IL-10 level at 4 weeks but not at 8 and 12 weeks. Renal IL-10 level increased while serum creatinine decreased significantly in IL-10 group at 12 weeks compared to PBS or YFP controls. Immunohistochemical staining showed unchanged total T cells (CD3) and B cells (CD45R/B220), decreased cytotoxic T cells (CD8), macrophages (CD68) and increased CD4+ and FoxP3+ cells in IL-10 group. In summary, intrarenal IL-10 inhibited the allograft rejection while modulated immune response.

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

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    Isabella Dash

    2010-12-01

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

  19. Coexistence of subacute thyroiditis and renal cell carcinoma: a paraneoplastic syndrome

    OpenAIRE

    Algün, Ekrem; ALICI, Süleyman; Topal, Cevat; Ugras, Serdar; Erkoç, Reha; Sakarya, M.Emin; Özbey, Nese

    2003-01-01

    RENAL CELL CARCINOMA IS CHARACTERIZED by varied manifestations, which include unusual metastatic sites and paraneoplastic and vascular syndromes. We describe the case of a 57-year-old man who presented with high fever, weight loss, palpitations and a tender goitre. We suggest that, in this patient, subacute thyroiditis manifested as a paraneoplastic syndrome of renal cell carcinoma.

  20. Children with chronic renal failure have reduced numbers of memory B cells.

    NARCIS (Netherlands)

    Bouts, A.H.M.; Davin, J.C.; Krediet, R.T.; Monnens, L.A.H.; Nauta, J.; Schröder, C.H.; Lier, R.A.W. van; Out, T.A.

    2004-01-01

    Reduced serum IgG and subclass levels have been demonstrated in children with chronic renal failure. To study possible causes of this reduction, we analysed B cell subset composition, T helper cell frequencies and immunoglobulin (Ig) production capacity in vitro in children with chronic renal failur

  1. The Autophagoproteasome a Novel Cell Clearing Organelle in Baseline and Stimulated Conditions.

    Science.gov (United States)

    Lenzi, Paola; Lazzeri, Gloria; Biagioni, Francesca; Busceti, Carla L; Gambardella, Stefano; Salvetti, Alessandra; Fornai, Francesco

    2016-01-01

    Protein clearing pathways named autophagy (ATG) and ubiquitin proteasome (UP) control homeostasis within eukaryotic cells, while their dysfunction produces neurodegeneration. These pathways are viewed as distinct biochemical cascades occurring within specific cytosolic compartments owing pathway-specific enzymatic activity. Recent data strongly challenged the concept of two morphologically distinct and functionally segregated compartments. In fact, preliminary evidence suggests the convergence of these pathways to form a novel organelle named autophagoproteasome. This is characterized in the present study by using a cell line where, mTOR activity is upregulated and autophagy is suppressed. This was reversed dose-dependently by administering the mTOR inhibitor rapamycin. Thus, we could study autophagoproteasomes when autophagy was either suppressed or stimulated. The occurrence of autophagoproteasome was shown also in non-human cell lines. Ultrastructural morphometry, based on the stochiometric binding of immunogold particles allowed the quantitative evaluation of ATG and UP component within autophagoproteasomes. The number of autophagoproteasomes increases following mTOR inhibition. Similarly, mTOR inhibition produces overexpression of both LC3 and P20S particles. This is confirmed by the fact that the ratio of free vs. autophagosome-bound LC3 is similar to that measured for P20S, both in baseline conditions and following mTOR inhibition. Remarkably, within autophagoproteasomes there is a slight prevalence of ATG compared with UP components for low rapamycin doses, whereas for higher rapamycin doses UP increases more than ATG. While LC3 is widely present within cytosol, UP is strongly polarized within autophagoproteasomes. These fine details were evident at electron microscopy but could not be deciphered by using confocal microscopy. Despite its morphological novelty autophagoproteasomes appear in the natural site where clearing pathways (once believed to be

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

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    Thomas C. Wehler

    2008-01-01

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

  3. Diagnosis and Treatment of Chromophobe Cell Renal Carcinoma (Report of 3 cases)

    Institute of Scientific and Technical Information of China (English)

    XiaopingQi; KaoXingLin; ZhenjiangLi; XiaofengHuang; XiaowenDai

    2004-01-01

    OBJECTIVE To study the diagnosis and treatment of chromophobe cell renal carcinoma (CCRC). METHODS Three cases of CCRC were studied by analyzing the results of an operation, by light microscopy, immunohistochemistry, Hale's colloidal iron staining and electronmicroscopy (EMC). RFESULTS Doppler ultrasonic and CT features were not specific. Histopathology: Grossly the tumor tissue was homogeneous, light brown in color with central necrotic foci; Light microscopy: Macrocyte, fine reticular cytoplasm with clear cell border; Hale's colloidal iron staining: positive; positive EMA, CK19, vimentin, Ckpan, and negative S-100; EMC: numerous intracyto-plasmic membranous small cysts. All patients were followed up for 14.1-31 months (19.7 months on average), one patient had lung metastasis 11 months after resection of a G,~ tumor, two alive patients had no local recurrences and metastases. CONCLUSIONS CCRC is histo-pathologically, immunohistochemically and electron microscopically distinct from other renal cancers. Surgical tumor removal is the best way for treatment. It is probably a type of cancer with low malignant potential and favorable prognosis.

  4. 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

  5. Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma.

    Science.gov (United States)

    Lindahl, Bengt; Persson, Jan; Ranstam, Jonas; Willén, Roger

    2010-09-01

    Uterine clear cell carcinoma (UCC) and uterine papillary serous carcinoma (UPSC) are rare entities that differ in clinical behavior from endometrial adenocarcinoma. Compared with endometrioid adenocarcinoma, they more often metastasize early and more commonly in the upper abdomen including the omentum. Treatment programs of UCC and UPSC at different stages vary and range from no adjuvant therapy in stage Ia to a wide variety of chemotherapies and radiotherapies in more advanced stages. This study presents the outcome of 109 patients with UCC or UPSC treated according to essentially the same treatment program from May 1993 to December 2004. Most patients were treated with a simple hysterectomy with no further adjuvant treatment. In stage Ia, 2/46 patients died of their disease and amongst all the stages, 30/109 patients died of their disease. These survival outcomes are comparable to or better than those presented previously. PMID:20944161

  6. Should all patients with serous and clear cell endometrial carcinoma receive adjuvant chemotherapy?

    Science.gov (United States)

    Boren, Todd P; Miller, David S

    2010-11-01

    Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent two rare subtypes that have an increased risk of recurrence and worse overall survival compared with the more common endometrioid endometrial cancers. Meaningful data in the form of prospective randomized trials is lacking for both advanced and early-stage UPSC and UCCC. Data extrapolated from prospective trials in advanced endometrioid endometrial cancer and retrospective trials on early-stage UPSC suggest that adjuvant platinum and taxane-based chemotherapy may provide a survival benefit for these patients. Future trials specifically examining UPSC and UCCC are needed to elucidate the optimal treatment regimen for these patients. Given the current data, the option of chemotherapy should be considered in treatment-planning discussions for all patients with UPSC and UCCC. PMID:21118038

  7. 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.

  8. 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

  9. In search of suitable reference genes for gene expression studies of human renal cell carcinoma by real-time PCR

    Directory of Open Access Journals (Sweden)

    Kristiansen Glen

    2007-06-01

    Full Text Available Abstract Background Housekeeping genes are commonly used as endogenous reference genes for the relative quantification of target genes in gene expression studies. No conclusive systematic study comparing the suitability of different candidate reference genes in clear cell renal cell carcinoma has been published to date. To remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR measurements already recommended in various studies were examined with regard to their usefulness as reference genes. Results The expression of the potential reference genes was examined in matched malignant and non-malignant tissue specimens from 25 patients with clear cell renal cell carcinoma. Quality assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a mean RNA integrity number of 8.7 for all samples. The between-run variations related to the crossing points of PCR reactions of a control material ranged from 0.17% to 0.38%. The expression of all genes did not depend on age, sex, and tumour stage. Except the genes TATA box binding protein (TBP and peptidylprolyl isomerase A (PPIA, all genes showed significant differences in expression between malignant and non-malignant pairs. The expression stability of the candidate reference genes was additionally controlled using the software programs geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by normalizing the target gene ADAM9 using these two most stably expressed genes in comparison with up- and down-regulated housekeeping genes of the panel. Conclusion Our study demonstrated the suitability of the two housekeeping genes PPIA and TBP as endogenous reference genes when comparing malignant tissue samples with adjacent normal tissue samples from clear cell renal cell carcinoma. Both genes are recommended as reference genes for relative gene quantification in gene profiling studies either as single gene or preferably in combination.

  10. 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

  11. Sunitinib activates Axl signaling in renal cell cancer.

    Science.gov (United States)

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies. PMID:26815723

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

    Science.gov (United States)

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

    2012-09-01

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

  13. TECHNICAL CHARACTERISTICS OF LAPAROSCOPIC PARTIAL NEPHRECTOMY IN CASE OF RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    S. N. Dimitriad

    2014-01-01

    Full Text Available The paper describes the technical characteristics of laparoscopic partial nephrectomy in patients with renal cell carcinoma. It has been ascertained that the authors’ two-layer wound closure technique during laparoscopic partial nephrectomy allows to perform complex renal resection (a total RENAL scale score up to 10 during long-term warm ischemia time that does not differ significantly (p = 0.09 in duration of simpler laparoscopic partial nephrectomy (without opening the pelvicalyceal system. 

  14. TECHNICAL CHARACTERISTICS OF LAPAROSCOPIC PARTIAL NEPHRECTOMY IN CASE OF RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    S. N. Dimitriad

    2014-07-01

    Full Text Available The paper describes the technical characteristics of laparoscopic partial nephrectomy in patients with renal cell carcinoma. It has been ascertained that the authors’ two-layer wound closure technique during laparoscopic partial nephrectomy allows to perform complex renal resection (a total RENAL scale score up to 10 during long-term warm ischemia time that does not differ significantly (p = 0.09 in duration of simpler laparoscopic partial nephrectomy (without opening the pelvicalyceal system. 

  15. Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

    OpenAIRE

    Jensen, Thomas Buus; Cheema, Muhammad Umar; Szymiczek, Agata; Damkier, Helle Hasager; Praetorius, Jeppe

    2015-01-01

    Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells i...

  16. Clear-cell variant urothelial carcinoma of the bladder: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Hossein Tezval

    2012-10-01

    Full Text Available Clear cell variants of transitional cell carcinomas (TCC of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

  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. Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis

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    Victor D. Liou

    2015-01-01

    Full Text Available Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC which metastasized to the base of his penis within 1 month of symptom onset. We also discuss the possible route of metastasis based on primary tumor size and location within the retroperitoneum.

  19. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    Science.gov (United States)

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

    2011-07-01

    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.

  20. Clear cell carcinoma of the uterine cervix: clinical characteristics and feasibility of fertility-preserving treatment

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    Jiang X

    2014-01-01

    Full Text Available Xiang Jiang, Ying Jin, Yan Li, Hui-Fang Huang, Ming Wu, Keng Shen, Ling-Ya Pan Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: The objective of this retrospective study was to analyze the clinical characteristics and prognosis of clear cell adenocarcinoma (CCA in the post-diethylstilbestrol (DES era and to evaluate the feasibility of fertility-preserving treatment. The records of 32 patients with CCAs who were treated at Peking Union Medical College Hospital from August 1986 to June 2012 were retrospectively reviewed. Three of the patients had undergone fertility-preserving treatment. The incidence of CCA among cervical adenocarcinomas was 15.2%. The median age was 38 years: 11 patients (34.4% were diagnosed before 30 years of age and two (6.3% after 70 years of age. Ten patients (31.2% were nulliparous. No patient had been exposed to DES. Twenty-nine patients (90.6% presented with obvious symptoms, and the cervix appeared abnormal in 26 patients (81.3%. Cervical Papanicolaou (Pap tests were abnormal in all four patients in whom they were performed (three had high-grade squamous intraepithelial lesions and one had atypical squamous cells of undetermined significance. The distribution by stage was 56.3% stage I, 34.4% stage II, 6.3% stage III, and 3.1% stage IV. Treatments mainly included surgery for patients with stage I to IIA CCA and radiochemotherapy for patients with advanced CCA. The overall 5-year progression-free survival was 72.2%. Patients with stage I to IIA CCA had better 5-year progression-free survival than did patients with stage IIB to IV CCA (81.5% versus 40.0%, P=0.003. The three patients who had undergone fertility-preserving treatment had no recurrences. CCA may also affect adolescents and children without prior DES exposure, who are often misdiagnosed as having functional uterine

  1. Tivozanib in the treatment of renal cell carcinoma

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    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

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

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    Li-Li Wen

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

  3. Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic Renal Cell Carcinoma

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    Krastan B. Blagoev

    2013-02-01

    Full Text Available Preclinical studies have suggested that sunitinib accelerates metastases in animals, ascribing this to inhibition of the vascular endothelial growth factor receptor or the tumor’s adaptation. To address whether sunitinib accelerates tumors in humans, we analyzed data from the pivotal randomized phase III trial comparing sunitinib and interferon alfa in patients with metastatic renal cell carcinoma. The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival. Specifically, neither longer sunitinib treatment nor a greater effect of sunitinib on tumors reduced survival. Sunitinib did reduce the tumor’s growth rate while administered, thereby improving survival, without appearing to alter tumor biology after discontinuation. Concerns arising from animal models do not apply to patients receiving sunitinib and likely will not apply to similar agents.

  4. 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.)

  5. Relationships between oxidative stress markers and red blood cell characteristics in renal azotemic dogs.

    Science.gov (United States)

    Buranakarl, C; Trisiriroj, M; Pondeenana, S; Tungjitpeanpong, T; Jarutakanon, P; Penchome, R

    2009-04-01

    Oxidative stress parameters and erythrocyte characteristics were studied in 15 normal healthy dogs and 33 renal azotaemic dogs from Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University. Dogs with renal azotaemia had reduced mean corpuscular volume (MCV) (PDogs with severe renal azotaemia had higher intraerythrocytic sodium contents (RBC-Na) (Pred blood cell catalase activity and glutathione and plasma malondialdehyde were unaltered while urinary malondialdehyde-creatinine ratio (U-MDA/Cr) increased significantly (Pdogs. Moreover, the U-MDA/Cr is a sensitive biochemical parameter which increased along with degree of renal dysfunction.

  6. 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.

  7. Renal T-cell lymphoma with cerebral metastasis in a dog with chronic canine ehrlichiosis

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    E.P. Lane

    2002-07-01

    Full Text Available A renal T-cell lymphoma with exclusive cerebral metastasis was diagnosed in a 5-year-old Staffordshire bull terrier bitch euthanased for aggression. This is the first recorded case of primary renal lymphoma in a dog. Immune suppression, due to chronic canine monocytic ehrlichiosis, mayaccount for the unusual primary site and metastatic patternof the tumour.

  8. Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Qiao Zhen-kui

    2013-01-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis and are inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs. {AU Query: Please verify that corrections made to previous sentence did not alter intended meaning}. In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1-MMP, TIMP-1, and TIMP-2 in renal tissue samples of renal cell cancer and examined the correlation between their expression and clinicopathological parameters. Methods Renal tissue samples from 76 patients with renal cell carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR was carried out on tumor and normal tissues. Results Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue (P Conclusions Mean MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the renal cell carcinomas was significantly higher than in the normal renal tissue.

  9. 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.

  10. Immune reactivity of cells from long-term rat renal allograft survivors

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, A.; Stuart, F.P.; Fitch, F.W.

    1978-11-01

    Lewis rats receiving an LBN kidney allograft demonstrate no signs of rejection if they are pretreated with donor spleen cells and antiserum reactive with the donor alloantigen. We examined the cellular reactivity of long-term kidney allograft survivors. Normal proliferative and cytolytic responses were obtained with spleen cells from long-term survivors, in marked contrast to the diminished responses of cells from neonatally tolerant rats or the heightened cytolytic response of cells from rats that had rejected a renal allograft. Serum from long-term renal allograft survivors as well as serum obtained from rats at the time of transplantation did not suppress proliferative or cytolytic responses of normal cells. The results of this study suggest that long-term renal allograft survivors possess the precursors of those cells which are responsible for proliferative and cytolytic responses in mixed leukocyte cultures, but that they have not been sensitized to their renal allograft.

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

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    Yaseen Alastal

    2015-04-01

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

  12. FDG-PET/CT in staging of clear cell odontogenic carcinoma.

    Science.gov (United States)

    Krishnamoorthy, R; Ravi Kumar, A S; Batstone, M

    2014-11-01

    Clear cell odontogenic carcinoma (CCOC) is a rare neoplasm; only 75 cases have been reported in the English language literature. They have a tendency for recurrence and a capacity to metastasize. There is very little known regarding the metabolic features of this tumour or the utility of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans in the staging and follow-up of these tumours. We present two cases of CCOC with their relevant FDG-PET/CT scan findings. The first patient had primary CCOC of the mandible that was FDG-avid, and the other had recurrence of CCOC of the anterior mandible and superomedial orbit that was not FDG-avid. FDG uptake in CCOC appears to be variable. Although FDG-PET/CT is useful in other head and neck cancers and has benefits compared to other imaging modalities, further studies are needed to investigate the sensitivity of FDG-PET/CT in CCOC. PMID:25015905

  13. Somatic copy number alterations associated with Japanese or endometriosis in ovarian clear cell adenocarcinoma.

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    Aikou Okamoto

    Full Text Available When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC include 1 a higher incidence among Japanese, 2 an association with endometriosis, 3 poor prognosis in advanced stages, and 4 a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH to identify somatic copy number alterations (SCNAs associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001 and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078 were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR. ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027. Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047, which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications.

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

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    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.

  15. 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

  16. 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.

  17. 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

  18. 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...

  19. Reference Genes for Gene Expression Analysis by Real-time Reverse Transcription Polymerase Chain Reaction of Renal Cell Carcinoma

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  20. Targeted therapy for renal cell carcinoma: The next lap

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    Ravindran Kanesvaran

    2014-01-01

    Full Text Available Advances in rationally targeted therapeutics over the last decade have transformed the clinical care of advanced kidney cancer. While oncologists consolidate the gains of the wave of new agents, comprising a panoply of anti-vascular endothelial growth factor multi-targeted tyrosine kinase inhibitors and inhibitors of the mammalian target of rapamycin (mTOR, there is an increasing sense that a plateau has been reached in the short term. It is sobering that all currently approved targeted therapies have not yielded durable remissions and remain palliative in intent. In the context of recent insights in kidney cancer biology, we review promising ongoing and future approaches for kidney cancer therapeutics aimed toward forging new paths in the systemic management of renal cell carcinoma. Broadly, candidate agents for such innovative strategies include immune check-point inhibitors, anti-cancer stem cell agents, next-generation anti-vascular endothelial growth factor receptor and anti-mTOR agents as well as more investigational agents in the preclinical and early clinical development settings.

  1. Research on the relationship between serum Th1/Th2, soluble index and renal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhang Yan; Wang Zhi-Qun

    2015-01-01

    Objective:To analyze the correlation between serum Th1/Th2 as well as a number of soluble index and renal cell carcinoma.Methods:The serum levels of Th1 cytokines such as IFN-γ, IL-2, TNF-α, Th2 cytokines such as IL-4, IL-6, IL-10, vascular endothelial growth factor VEGF, VEGFR-1, VEGFR-2 and soluble human major histocompatibility complex classⅠchain-related gene A protein (sMICA), carbonic anhydrase (CAIX) in 72 cases of different clinical stages of renal carcinoma patients and 30 normal controls were detected and compared with ELISA method.Results:The serum levels of Th1 cell cytokine of patients with renal were significantly lower than healthy control group, showing a negative correlation with the clinical stage; the serum levels of Th2 cell cytokine of patients with renal were significantly higher than healthy control group, showing a positive correlation with the clinical stage, P<0.05. The serum levels of VEGF, VEGFR-1, VEGFR-2, sMICA and CAIX of patients with renal were significantly higher than healthy control group and positively correlated with the clinical stage,P<0.05.Conclusions: A number of Th1/Th2 cytokines, VEGF, sMICA, CAIX can be used for auxiliary diagnosis of renal cell carcinoma. These indicators are closely related with clinical stages of renal cell carcinoma, thus can also be used in prognosis.

  2. Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma

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    Arash Akhavein

    2014-05-01

    Full Text Available Xp11 translocation renal cell carcinoma (TRCC is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor–targeted therapy in case of recurrence.

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

    NARCIS (Netherlands)

    Timmeren, Mirjan Miranda van

    2008-01-01

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

  4. One cases report:adult clear cell sarcoma of kidney%成人肾透明细胞肉瘤1例病例报道

    Institute of Scientific and Technical Information of China (English)

    江冬梅; 王凤玮

    2015-01-01

    Clear cell sarcoma of kidney(CCSK) is a rare and malignant sarcoma, whose the origin of organization is not clear,and most reports indicated the patients is children,but not adults.The sarcoma has hard prognosis and poor sur-vival rate.CCSK is similar to other renal malignant tumors very much in clinical and histological aspects,therefore,the differential diagnosis with other renal malignant tumor is very important.Now we report a case of an adult female pa-tients who was already diagnosed with CCSK of the kidney,and state the discrimination with CCSK of kidney and Wilms’tumor.%肾透明细胞肉瘤(CCSK)是一种组织来源尚未十分清楚的罕见软组织恶性肿瘤,该病多见于儿童,成人患者罕见。成人CCSK预后极差,生存期短。 CCSK临床表现和组织形态学与多种肾恶性肿瘤相似,误诊率较高,在患者预后和治疗方面,CCSK与其他肾恶性肿瘤差别较大,因此,CCSK与其他肾恶性肿瘤的鉴别诊断对于CCSK的确诊至关重要。本文报道我院1例已确诊为CCSK的成年女性患者,简要阐述该疾病与肾透明细胞癌、肾母细胞瘤的鉴别。

  5. 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.

  6. 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

  7. 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

  8. Survival of women with clear cell and papillary serous endometrial cancer after adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Type II (papillary serous and clear cell) endometrial carcinoma (EC) is a rare subgroup and is considered to have an unfavorable prognosis. The purpose of this retrospective analysis was to elucidate the meaning of adjuvant radiotherapy (RT) for clinical outcome and to define prognostic factors in these patients (pts). From 2004-2012 forty-two pts with type II EC underwent surgery followed by adjuvant RT at our department. Median age was 72 years. The majority were early stage carcinomas (FIGO I n = 27 [64.3%], FIGO II n = 4 [9.5%], FIGO III n = 11 [26.2%]. Seven pts (16.7%) received adjuvant chemotherapy (ChT). Pts were treated with external beam radiotherapy (EBRT) and brachytherapy (IVB) boost. Five-year local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) were 85.4%, 78%, and 64.5% respectively. LRFS was better with lower pT stage, without lymphangiosis (L0), without haemangiosis (V0) and negative resection margins (R0). DMFS was prolonged in lymph node negatives (N0), L0, V0 and R0. OS was improved in younger pts, N0, L0, V0 and after lymphadenectomy (LNE). Multivariate analysis revealed haemangiosis (V1) as the only independent prognostic factor for OS (p = .014) and DMFS (p = .008). For LRFS pT stage remained as an independent prognostic factor (p = .028). Adjuvant RT with EBRT/IVB ensures adequate local control in type II EC, but control rates remain lower than in type I EC. A benefit of additional adjuvant ChT could not be demonstrated and a general omission of EBRT cannot be recommended at this point. Lymphovascular infiltration and pT stage might be the best predictive factors for a benefit from combined local and systemic treatment

  9. Livin在肾透明细胞癌中的表达意义%Expression of livin in clear cell carcinoma of kidney

    Institute of Scientific and Technical Information of China (English)

    王凤龙; 周林玉; 谈宜傲; 王子夜; 王辰; 谢金波

    2012-01-01

    Objective To explore the expression of Livin and its significance in clear cell carcinoma of kidney. Methods The expression of Livin was examined by immunohistochemistry in 63 cases of clear cell carcinoma of kidney, 38 cases of normal renal tissues. Results of Livin expression were compared with tumor size, clinical stage, pathology grade and lymphatic metastasis to make the correlation analysis. Results The positive rate of Livin expression was obviously higher in RCCC specimens than in normal renal tissues(P 〈 0. 05) ,and correlated with tumor size(P 〈0.05) ,but independent of pathology grade(P 〉0.05). It was higher in clear cell carcinoma of kidney with lymphatic metastasis than without (P 〈0. 05) , With the increase of clinical stage, the expression of OPN showed heightening in corresponding (P 〈0.05). Conclusion Livin was highly expressed in RCCC specimens and closely correlated with tumor size, clinical stage and lymphatic metastasis.%目的 探讨存活蛋白(Livin)在肾透明细胞癌(RCCC)组织中的表达及意义.方法 采用免疫组化的方法对63例RCCC组织和38例正常肾组织中Livin的表达进行检测.分析它的表达变化与RCCC肿瘤大小,临床分期,病理分级及淋巴结转移的关系.结果 Livin在RCCC组织中的表达阳性率明显高于正常肾组织(P<0.05),并与肿瘤大小有关(P<0.05).有淋巴结转移者明显高于无淋巴结转移者( P<0.05),并且随着临床分期增加其表达亦明显增高( P<0.05),与病理分级无关(P>0.05).结论 Livin在RCCC组织中表达明显上调,并且与肿瘤的大小,临床分期及淋巴结转移密切相关.

  10. Prolonged survival after sequential multimodal treatment in metastatic renal cell carcinoma: two case reports and a review of the literature

    Directory of Open Access Journals (Sweden)

    Syrios John

    2012-09-01

    Full Text Available Abstract Introduction In this case series and short review of the literature, we underline the impact of nephrectomy combined with sequential therapy based on cytokines, antiangiogenic factors, and mammalian target of rapamycin inhibitors along with metastasectomy on overall survival and quality of life in patients with metastatic clear cell renal carcinoma. Case presentation In the first of two cases reported here, a 53-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer and relapsed with a bone metastasis in his right humerus. He was treated with closed nailing and cytokine-based chemotherapy. For 5 years, the disease was stable and he had great improvement in quality of life. Subsequently, the disease relapsed in his lymph nodes, lung, and thorax soft tissue. He was then treated with antiangiogenic factors and mammalian target of rapamycin inhibitors. The disease progressed until September 2009, when he died of allergic shock during a blood transfusion, 9 years after the initial diagnosis of renal cell cancer. In the second case, a 54-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer. A year later, the disease progressed to his neck lymph nodes, and cytokine-based chemotherapy was initiated. While he was on cytokines, a solitary pulmonary nodule appeared and he underwent a metastasectomy. Nine months later, magnetic resonance imaging of his brain revealed a focal right occipitoparietal lesion, which was resected. After two years of active surveillance, the disease relapsed as a pulmonary metastasis and he was treated with an antiangiogenic factor. Further progressions presenting as enlarged axillary lymph nodes, chest soft tissue lesions, and thoracic spine bone metastases were sequentially observed. He then received a first-generation mammalian target of rapamycin inhibitor, an antiangiogenic factor, and later a second-generation mammalian target of rapamycin inhibitor and

  11. Differentiations of transplanted mouse spermatogonial stem cells in the adult mouse renal parenchyma in vivo

    Institute of Scientific and Technical Information of China (English)

    Da-peng WU; Da-lin HE; Xiang LI; Zhao-hui LIU

    2008-01-01

    Aim:Spermatogonial stem cells can initiate the process of cellular differentia-tion to generate mature spermatozoa, but whether it possess the characteristic of pluripotency and plasticity, similar to embryonic stem cells, has not been elucidated. This study was designed to evaluate the differentiation potential of spermatogonial stem cells into renal cells in vivo. Methods: Neonatal mouse spermatogonial stem cells were transplanted into mature male mice lacking en-dogenous spermatogenesis. The restoration of fertility in recipient males was observed. Spermatogonial stem cells were then injected into renal parenchyma of mature female mice to make a new extracellular environment for differentia-tion. Fluorescence in situ hybridization technology (FISH) was used to detect the expression of chromosome Y in recipient renal tissues. To determine the type of cells differentiated from spermatogonial stem cells, the expression of ricinus communis agglutinin, vimentin, CD45, and F4/80 proteins were examined in the renal tissues by immunohistochemistry. Results: The proliferation of seminiferous epithelial cells was distinctly observed in seminiferous tubules of transplanted testes, whereas no regeneration of spermatogenesis was observed in non-transplanted control testes. In transplanted female renal tissues, FISH showed a much stronger immuno-fluorescence signal of chromosome Y in the nucleolus of epithelial cells of the renal tubule and podocytes of the glomerulus. Conclusion: The spermatogonial stem cells were successfully purified from mouse testicles. This finding demonstrated that spermatogonial stem cells could not only restore damaged spermatogenesis, but were also capable of differentiat-ing into mature renal parenchyma cells in vivo.

  12. High Telomerase Activity Correlates with the Stabilities of Genome and DNA Ploidy in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hideki Izumi

    2002-01-01

    Full Text Available Malignant tumors have telomerase activity, which is thought to play a critical role in tumor growth. However, the relation between telomerase activity and genomic DNA status in tumor cells is poorly understood. In the present study, we examined telomerase activity in 13 clear cell type renal cell carcinomas (CRCCs with similar clinicopathologic features by telomeric repeat amplification protocol assay (TRAP. Based on TRAP assay results, we divided the CRCCs into two groups: a high telomerase activity group and a low/no telomerase activity group. We then analyzed genomic aberration, DNA ploidy, and telomere status in these two groups by comparative genomic hybridization (CGH, laser scanning cytometry (LSC, and telomere-specific fluorescence in situ hybridization (T-FISH, respectively. CGH showed the high telomerase activity group to have fewer genomic changes than the low/no telomerase activity group, which had many genomic aberrations. Moreover, with LSC, DNA diploid cells were found more frequently in the high telomerase activity group than in the low/no telomerase activity group. In addition, T-FISH revealed strong telomere signal intensity in the high telomerase activity group compared with that of the low/no telomerase activity group. These results suggest that telomerase activity is linked to genomic DNA status and that high telomerase activity is associated with genomic stability, DNA ploidy, and telomere length in CRCC.

  13. 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.

  14. 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

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

    LENUS (Irish Health Repository)

    Bhargava, A

    2012-06-01

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

  16. Atypical presentation of primary renal squamous cell cancer: a case report

    Directory of Open Access Journals (Sweden)

    Mrinal Pahwa

    2014-02-01

    Full Text Available Renal squamous cell cancer is one of the rare primary urothelial tumors with only a handful of cases reported in literature. Because of high grade, advanced and late presentation, they herald a grave prognosis. They are frequently associated with calculus disease, smoking, phenacetin consumption and foci of squamous metaplasia due to chronic irritation. Nephroureterectomy is the treatment of choice for such tumors. We hereby present a case of 59 year old female who presented with squamous cell cancer of renal pelvis. The case presented here is different from what has already been reported in literature, as the patient had no antecedent risk factors for renal squamous cell carcinoma.-------------------------------------------------Cite this article as: Pahwa M, Pahwa AR, Girotra M, Chawla A. Atypical presentation of primary renal squamous cell cancer: a case report. Int J Cancer Ther Oncol 2014; 2(1:02015.DOI: http://dx.doi.org/10.14319/ijcto.0201.5

  17. Simultaneous Renal Cell Carcinoma and Giant Retroperitoneal Liposarcoma Involving Small Intestine.

    Science.gov (United States)

    Reznichenko, Aleksandr A

    2016-01-01

    Background. The concomitant occurrence of a renal cell carcinoma and retroperitoneal sarcoma is extremely rare with only few cases being reported. Methods. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma involving small intestine. Surgical resection of retroperitoneal sarcoma and simultaneous right nephrectomy were performed. Results. Patient developed recurrent and metastatic disease and underwent debulking surgery following by chemotherapy. Despite aggressive behavior of the retroperitoneal sarcomas, patient is currently (7 years after simultaneous resection and nephrectomy) recurrence-free. Conclusions. Complete surgical resection is the mainstay of therapy for both renal cell carcinoma and retroperitoneal sarcoma. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma. Debulking surgery and chemotherapy were helpful in our case. PMID:27595033

  18. Cystic local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy in a hemodialysis patient.

    Science.gov (United States)

    Ito, Kazuyo; Takagi, Toshio; Kondo, Tsunenori; Yoshida, Kazuhiko; Iizuka, Junpei; Kobayashi, Hirohito; Tomita, Eri; Hashimoto, Yasunobu; Tanabe, Kazunari

    2014-03-01

    Although local recurrence of renal cell carcinoma after laparoscopic radical nephrectomy is sometimes reported, cystic local recurrence of renal cell carcinoma has rarely been reported. We report the case of a 59-year-old man with hemodialysis who developed cystic local recurrence of renal cell carcinoma accompanied by acquired cystic disease of the kidney in the retroperitoneal space after laparoscopic radical nephrectomy. A cystic tumor of 5.1 cm in diameter occurred in the left retroperitoneal space 15 months after left laparoscopic radical nephrectomy, and enlarged to 7.2 cm in diameter with enhanced mass along the wall of the cyst 36 months after surgery. The cystic tumor was removed and showed local recurrence of renal cell carcinoma on pathological examination.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-10-15

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

  20. Metastatic Renal Cell Carcinoma Presenting as Nasal Mass: Case Report and Review of Literature.

    Science.gov (United States)

    Mahajan, Ritesh; Mayappa, Nagaraj; Prashanth, V

    2016-09-01

    Sinonasal neoplasms are rare and exceptional site for metastatic tumours and comprising CT scan revealed a tumour in the right nasal cavity and maxillary sinus. The presence of primary renal cell carcinoma was recognized only after surgical removal of metastatic tumour. Very few reports have been presented in literature of metastatic renal cell carcinoma in the sinonasal region. We present this case to document its occurrence; highlight the rarity, presentation and difficulties in diagnosis and treatment along with review of literature. PMID:27508143

  1. Papillary renal cell carcinoma. A morphologic and cytogenetic study of 11 cases.

    OpenAIRE

    Kovacs, G

    1989-01-01

    Most renal cell carcinomas are characterized by constant loss of the 3p13-pter chromosome segment and a frequent gain of the 5q22-qter segment. A comparative histologic and cytogenetic investigation of large series of renal cell carcinomas now shows that purely papillary tumors differ from the more common nonpapillary form not only in their morphologic characteristic, but also in karyotype changes observed. All of the 11 papillary tumors of this study failed to show any rearrangement of the c...

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

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

  4. Effects of Hydroxyapatite Nanoparticles on Apoptosis and Invasion of Human Renal Cell Carcinoma 786-0 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-xin; KONG Xiang-bo; ZHAO Xu; ZHANG Ling; HOU Yi; HAN Wei; WANG Kai-chen; GUO Bao-feng; LIU Ying; CHANG Xi-hua; WANG Wei-hua; NA Wan-li

    2011-01-01

    Renal cell carcinoma is the most common cancer of the kidney, and resistant to traditional therapies. The aim of this study is to investigate the effects of hydroxyapatite nanoparticles on human renal cell carcinoma 786-0 cells. Cell proliferation was assessed with an 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide(MTT)staining kit. The apoptosis assay was assessed with an FITC Annexin V Apoptosis Detection Kit. Caspase-3 and caspase-12 were detected by immunocytochemical staining and semi-quantitative RT-PCR. Cell wound healing assay was used to ensure cell motility. Matrigel invasion assay was analysed via transwell chambers. Our results showed that hydroxyapatite nanoparticles significantly reduced cell proliferation, invasion and induced apoptosis of 786-0 cells. The inhibiting action may have relation with up-regulated caspase-12, leading the cells to apoptosis. This study suggests that hydroxyapatite nanoparticles may be an effective and delivery system for renal cell carcinoma therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Rachna Raman

    2015-01-01

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

  7. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    Renal angiomyolipoma is a rare lesion composed of smooth muscle cells, adipose tissue and abnormal vessels. It is currently classified as a benign, non-epithelial renal tumor. It has a high incidence in patients suffering from tuberous sclerosis but is more frequently found as an isolated renal...... features. However, a smaller number of smooth muscle cells also contained lipid, thus simulating an intermediate cell stage between adipose- and smooth muscle cells. The abnormal thickening of the subendothelial spaces contained collagen fibrils in a homogeneous matrix, fibroblast-like cells and non......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

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

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    José Martínez

    1989-01-01

    Full Text Available

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

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

  9. Interventions to improve chronic cyclosporine A nephrotoxicity through inhibiting renal cell apoptosis: a systematic review

    Institute of Scientific and Technical Information of China (English)

    XIAO Zheng; LI Cheng-wen; SHAN Juan; LUO Lei; FENG Li; LU Jun; LI Sheng-fu

    2013-01-01

    Objective To reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies,we analyzed all relevant studies about interventions in renal cell apoptosis.Data sources We collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010),Embase (1980 to July 2010) and ISI (1986 to July 2010),evaluated their quality,extracted data following PICOS principles and synthesized the data.Study selection We included all relevant studies about interventions in CsA-induced renal cell apoptosis no limitation of research design and language) and excluded the duplicated articles,meeting abstracts and reviews without specific data.Results There were three kinds of intervention,include anti-oxidant (sulfated polysaccharides,tea polyphenols,apigenin,curcumin,spirulina,etc),biologics (recombinant human erythropoietin (rhEPO),a murine pan-specific transforming growth factor (TGF)-beta-neutralizing monoclonal antibody1D11,cartilage oligomeric matrix protein (COMP)-angiopoietin-1 and hepatocyte growth factor (HGF) gene),and other drugs (spironolactone,rosiglitazone,pirfenidone and colchicine).These interventions significantly improved the CCN,renal cell apoptosis and renal dysfunction through intervening in four apoptotic pathways in animals or protected renal cells from apoptosis induced by CsA and increased cell survival through respectively four pathways in vitro.Conclusions There are three group interventions for CCN.Especially anti-oxidant drugs can significantly improve CCN,renal cell apoptosis and renal dysfunction.Many drugs can improve CCN through intervening in Fas/Fas ligand or mitochondrial pathway with sufficient evidences.Angiotensin Ⅱ,nitric oxide (NO) and endoplasmic reticulum (ER) pathways will be new targets for CCN.

  10. Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells.

    Science.gov (United States)

    Yang, Feng-Qiang; Wang, Ji-Jiao; Yan, Jia-Sheng; Huang, Jian-Hua; Li, Wei; Che, Jian-Ping; Wang, Guang-Chun; Liu, Min; Zheng, Jun-Hua

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene. PMID:25419360

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

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    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.

  12. Splenic and portal vein thrombosis in pancreatic metastasis from Renal cell carcinoma

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    Loos Martin

    2006-05-01

    Full Text Available Abstract Background Pancreatic metastases from previously treated renal cell carcinoma are uncommon. Surgical resection of pancreatic metastasis remains the only worthwhile modality of treatment. Case presentation A case where pancreatic metastasis from previously resected right sided renal cell carcinoma was resected with a subtotal left pancreatectomy is described. An unusual feature was the presence of a large splenic vein tumor thrombus extending into the portal vein with associated portal hypertension. The patient underwent an uneventful portal vein resection with primary anastomosis. Conclusion This is possibly the first documented case of portal vein renal tumor thrombosis in a case of isolated pancreatic metastasis from previously operated renal cell carcinoma in published world surgical literature.

  13. The ISUP system of staging, grading and classification of renal cell neoplasia

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    Hemamali Samaratunga

    2014-07-01

    Full Text Available There have been significant changes in the staging, classification and grading of renal cell neoplasia in recent times. Major changes have occurred in our understanding of extra-renal extension by renal cell cancer and how gross specimens must be handled to optimally display extra-renal spread. Since the 1981 World Health Organization (WHO classification of renal tumors, in which only a handful of different entities were reported, many new morphological types have been described in the literature, resulting in 50 different entities reported in the 2004 WHO classification. Since 2004, further new entities have been recognized and reported necessitating an update of the renal tumor classification. There have also been numerous grading systems for renal cell carcinoma with Fuhrman grading, the most widely used system. In recent times, the prognostic value and the applicability of the Fuhrman grading system in practice has been shown to be, at best, suboptimal. To address these issues and to recommend reporting guidelines, the International Society of Urological Pathology (ISUP undertook a review of adult renal neoplasia through an international consensus conference in Vancouver in 2012. The conduct of the conference was based upon evidence from the literature and the current practice amongst recognized experts in the field. Working groups selected to deal with key topics evaluated current data and identified points of controversy. A pre-meeting survey of the ISUP membership was followed by the consensus conference at which a formal ballot was taken on each key issue. A 65% majority vote was taken as consensus. This review summarizes the outcome and recommendations of this conference with regards to staging, classification and grading of renal cell neoplasia.

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

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    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.

  15. Clear cell adenocarcinoma of the uterine cervix with malignant pleural effusion in a 29-year old female- A case report

    Directory of Open Access Journals (Sweden)

    Dipti R. Samanta

    2015-07-01

    Full Text Available Primary adenocarcinoma of cervix constitute about 7-15% of all cervical cancer. Clear cell carcinoma, a form of cervical adenocarcinoma is a very rare tumor constituting only 4% of cervical carcinoma. Risk factor and pathogenesis of this disease are not exactly revealed. Intrauterine exposure to diethylstilbestrol and associated non-steroidal estrogen during pregnancy before 18 weeks is the only risk factor. Here we report an unusual case of clear cell carcinoma of cervix presented with bilateral pleural effusion, cytology of which shows adenocarcinoma. This is a rare case since patient had no history of diethylstilbestrol exposure and presented with bilateral pleural effusion. This is the first described case report of clear cell carcinoma of cervix with upfront malignant pleural effusion. [Int J Res Med Sci 2015; 3(7.000: 1795-1797

  16. Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation.

    Science.gov (United States)

    Di Giusto, Gisela; Flamenco, Pilar; Rivarola, Valeria; Fernández, Juan; Melamud, Luciana; Ford, Paula; Capurro, Claudia

    2012-12-01

    We have previously demonstrated that in renal cortical collecting duct cells (RCCD(1)) the expression of the water channel Aquaporin 2 (AQP2) raises the rate of cell proliferation. In this study, we investigated the mechanisms involved in this process, focusing on the putative link between AQP2 expression, cell volume changes, and regulatory volume decrease activity (RVD). Two renal cell lines were used: WT-RCCD(1) (not expressing aquaporins) and AQP2-RCCD(1) (transfected with AQP2). Our results showed that when most RCCD(1) cells are in the G(1)-phase (unsynchronized), the blockage of barium-sensitive K(+) channels implicated in rapid RVD inhibits cell proliferation only in AQP2-RCCD(1) cells. Though cells in the S-phase (synchronized) had a remarkable increase in size, this enhancement was higher and was accompanied by a significant down-regulation in the rapid RVD response only in AQP2-RCCD(1) cells. This decrease in the RVD activity did not correlate with changes in AQP2 function or expression, demonstrating that AQP2-besides increasing water permeability-would play some other role. These observations together with evidence implying a cell-sizing mechanism that shortens the cell cycle of large cells, let us to propose that during nutrient uptake, in early G(1), volume tends to increase but it may be efficiently regulated by an AQP2-dependent mechanism, inducing the rapid activation of RVD channels. This mechanism would be down-regulated when volume needs to be increased in order to proceed into the S-phase. Therefore, during cell cycle, a coordinated modulation of the RVD activity may contribute to accelerate proliferation of cells expressing AQP2. PMID:22786728

  17. CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-kappaB.

    Science.gov (United States)

    Sánchez-López, Elsa; Rayego, Sandra; Rodrigues-Díez, Raquel; Rodriguez, Javier Sánchez; Rodrigues-Díez, Raúl; Rodríguez-Vita, Juan; Carvajal, Gisselle; Aroeira, Luiz Stark; Selgas, Rafael; Mezzano, Sergio A; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

    2009-07-01

    Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-kappaB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-kappaB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-gamma, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-kappaB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-kappaB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-kappaB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-kappaB pathway. PMID:19423687

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

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    Fernando G. Abarzua-Cabezas

    2015-02-01

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

  19. Clear Cell Carcinoma Presented as a Large Polypoid Mass Expanding the Vaginal Fornix: Report of Two Cases

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    Kim, Ji Young; Cho, Jae Ho [Dept. of Radiology, College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2012-11-15

    Primary clear cell carcinoma of the vagina or uterine cervix is a very rare tumor. We report radiologic findings of two cases of clear cell carcinoma, arising in the vagina and uterine cervix in a 16-year-old and a 26-year-old female. These were presented as a large polypoid mass with a stalk and expanding the vaginal fornix. One case with ultrasonography showed relatively homogeneous echoic solid mass; the other case with a CT showed heterogeneously and strongly enhancing mass. All of the two cases showed non-specific signal intensity with heterogeneous and strong enhancement on MRI.

  20. 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.

  1. Regression of metastatic clear cell kidney cancer with interleukin-2 treatment following nivolumab (anti-PD-1) treatment.

    Science.gov (United States)

    Brayer, Jason; Fishman, Mayer

    2014-04-01

    Aldesleukin [interleukin-2 (IL-2)] induces durable complete responses in some kidney cancer and melanoma patients. Nivolumab is an investigational antibody drug targeting programmed death-1 (PD-1) as a treatment, demonstrating activity in multiple cancer types. An expanding complement of immunotherapeutics raises important issues regarding the best way to use them. There are issues beyond identifying an agent that provides the superior front-line response: when does one therapy potentiate another immune therapy? When is the capacity of immune response exhausted and an approach without immune mechanism the better therapy? In this case report, we present a patient with metastatic renal cell carcinoma with no tumor regression evident on a PD-1 blockade (given on an investigational trial), who then achieved near-complete response to bolus high-dose IL-2 therapy, maintaining a persistent response off therapy. This case emphasizes on the need to develop improved predictors of response to immune therapies, especially as they can be applied to optimize sequential immunotherapeutic modalities versus predict when to turn to alternative targeted agents in renal cell carcinoma, and is an example of efficacious IL-2 application as a second-line treatment. PMID:24598453

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

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    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;}

  3. 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

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

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    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.

  5. IMMUNOLOGICAL MONITORING OF BIOTHERAPY FOR DISSEMINATED RENAL-CELL CARCINOMA

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    O. E. Molchanov

    2009-01-01

    Full Text Available Objective: to assess a role of immunomonitoring in patients with disseminated renal-cell carcinoma.  Subjects and methods. One hundred and seventy-five patients treated in 1998 to 2008 were followed up. The patients received various immunochemotherapy regimens including interleukin-2 (IL-2, interferon-α (IFN-α, Xeloda, cyclophosphamide. The immune status, including lymphocytes and their subpopulations, cytokine components (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12; IFN-α, IFN-γ; tumor necrosis factor-α (TNF-α, immunoglobulins (IgA, IgG, IgM, complement components (C1q, C3, C3a, C4, C5a, was evaluated before treatment and at therapy-free intervals. Results.  The time course of changes in cytokines (IL-6, IL-8, IL-10; TNF-α and IFN-γ and some lymphocyte subpopulations (CD4+CD8+, CD3-CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+Foxp3 greatly differs in patients who belong to different prognostic groups according to the Memorial Sloan-Kettering Cancer Center (MSKCC inclusion criteria. Multivariate analysis has shown that the levels of IL-6 (spontaneous and induced production, IL-8 (spontaneous and induced production, TNF-α (spontaneous production, IFN-γ (induced production, NK T cells (CD3+CD16+CD56+, regulatory T cells (CD4+CD25+Foxp3 affect survival. Integration of the ab